{ "synthetic_only": true, "clinical_review_status": "pending", "result": { "patient_id": "SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE", "disease_id": "DIS-DLBCL-NOS", "algorithm_id": "ALGO-DLBCL-1L", "default_indication_id": "IND-DLBCL-1L-RCHOP", "alternative_indication_id": "IND-DLBCL-1L-POLA-R-CHP", "default_indication": { "id": "IND-DLBCL-1L-RCHOP", "plan_track": "standard", "applicable_to": { "disease_id": "DIS-DLBCL-NOS", "line_of_therapy": 1, "stage_requirements": [], "biomarker_requirements_required": [ { "biomarker_id": "BIO-CD20-IHC", "required": true, "value_constraint": "positive (CD20+)" }, { "biomarker_id": "BIO-DLBCL-IPI", "required": true, "value_constraint": "IPI 0-5; R-CHOP preferred for IPI 0-1; for IPI ≥2 see Pola-R-CHP" }, { "biomarker_id": "BIO-HBV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; HBsAg+ or anti-HBc+ → entecavir prophylaxis mandatory before first rituximab dose; engine consumes the input to fire RF-UNIVERSAL-HBV-REACTIVATION-RISK)" }, { "biomarker_id": "BIO-HCV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; anti-HCV+ → reflex BIO-HCV-RNA; coordinate DAA with hepatology; does not change R-CHOP regimen choice)" }, { "biomarker_id": "BIO-HIV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; HIV+ → cART throughout, PJP/MAC prophylaxis if CD4 < 200, CNS prophylaxis regardless of CNS-IPI; integrase-inhibitor backbone preferred to avoid ritonavir-vincristine interaction)" }, { "biomarker_id": "BIO-DLBCL-COO-HANS", "required": false, "value_constraint": "GCB or non-GCB by Hans algorithm — non-GCB has worse R-CHOP outcomes; some centres consider R-CHOEP for non-GCB" }, { "biomarker_id": "BIO-BCL2-EXPRESSION-IHC", "required": false, "value_constraint": "BCL2-IHC ≥50% combined with MYC-IHC ≥40% defines double-expressor (DEL) phenotype — poorer prognosis but not an excluder; HGBL-DH (FISH double-hit) must be ruled out" } ], "biomarker_requirements_excluded": [], "demographic_constraints": { "ecog_max": 3 } }, "recommended_regimen": "REG-R-CHOP", "concurrent_therapy": [], "followed_by": [], "evidence_level": "high", "strength_of_recommendation": "strong", "nccn_category": "1", "expected_outcomes": { "overall_response_rate": "~85% (≥PR after 6 cycles)", "complete_response": "~65-70%", "progression_free_survival": "Median PFS ~5 years for low-IPI; ~2 years for high-IPI", "overall_survival_5y": "~60% overall (low-IPI ~80%, high-IPI ~55%)" }, "hard_contraindications": [ "CI-HBV-NO-PROPHYLAXIS", "CI-LVEF-LOW-FOR-ANTHRACYCLINE" ], "red_flags_triggering_alternative": [ "RF-DLBCL-HIGH-IPI" ], "required_tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT", "TEST-LDH", "TEST-B2-MICROGLOBULIN", "TEST-HBV-SEROLOGY", "TEST-HCV-ANTIBODY", "TEST-HIV-SEROLOGY", "TEST-CD20-IHC", "TEST-PET-CT", "TEST-ECHO", "TEST-LN-EXCISIONAL-BIOPSY", "TEST-FLOW-CYTOMETRY", "TEST-FISH-PANEL", "TEST-PREGNANCY", "TEST-BM-ASPIRATE", "TEST-BM-TREPHINE" ], "desired_tests": [], "rationale": "Long-standing 1L standard for newly-diagnosed DLBCL NOS, used for the past 20+ years across NCCN, ESMO, EHA. ~60% overall cure rate; outcomes highly dependent on IPI. Replaced PreCHOP regimens after the rituximab era (RCT data from late 1990s/early 2000s). Default for low-IPI (0-1) patients; for IPI ≥2, modern evidence (POLARIX 2022) favors Pola-R-CHP if accessible (see IND-DLBCL-1L-POLA-R-CHP).\n", "rationale_ua": "R-CHOP (ритуксимаб + циклофосфамід + доксорубіцин + вінкристин + преднізолон) є багаторічним стандартом першої лінії (перша лінія) для вперше діагностованої ДВКЛ NOS, що застосовується понад 20 років в рекомендаціях NCCN, ESMO, EHA. Загальний рівень виліковування ~60%; результати суттєво залежать від IPI. Стандарт вибору для IPI 0-1; при IPI >=2 сучасні дані (POLARIX 2022) свідчать на користь Pola-R-CHP за наявності доступу (div. IND-DLBCL-1L-POLA-R-CHP). NCCN Категорія 1. Схема: ритуксимаб 375 mg/m2 + циклофосфамід 750 mg/m2 + доксорубіцин 50 mg/m2 + вінкристин 1.4 mg/m2 (макс. 2 мг) + преднізолон 100 мг (дні 1-5) q21d x 6 циклів. CNS-профілактика (HD-MTX intercalated) при CNS-IPI >=4 або уражених локалізаціях (тестикули, груди, нирки/наднирники, параназальні синуси). Базовий скринінг HBV обов'язковий; ентекавір при HBsAg+ або anti-HBc+. Базовий ЕХОКГ для LVEF >=50% (антрациклінова кардіотоксичність). Вінкристин вводити ВИКЛЮЧНО внутрішньовенно - інтратекальне введення є ФАТАЛЬНИМ. Рецидивний/рефрактерний (relapsed/refractory) ДВКЛ після R-CHOP потребує переходу на 2L (сальвадж хіміотерапія -> аутоТГСК для придатних; CAR-T для р/р).\n", "ukrainian_review_status": "pending_clinical_signoff", "ukrainian_drafted_by": "claude_extraction", "draft_revision": 2, "sources": [ { "source_id": "SRC-NCCN-BCELL-2025", "position": "supports", "relevant_quote_paraphrase": "R-CHOP is a Category 1 preferred regimen for newly-diagnosed DLBCL across all IPI groups; Pola-R-CHP is preferred Category 1 for IPI ≥2 where accessible" }, { "source_id": "SRC-ESMO-LYMPHOMA-2025", "position": "supports", "relevant_quote_paraphrase": "ESMO 2024 codifies R-CHOP × 6 as 1L standard for DLBCL NOS; Pola-R-CHP preferred for IPI ≥3 per POLARIX" } ], "known_controversies": [ { "topic": "R-CHOP vs Pola-R-CHP for IPI ≥2 1L DLBCL", "positions": [ { "position": "Pola-R-CHP preferred for IPI ≥2 where accessible (POLARIX evidence)", "sources": [ "SRC-NCCN-BCELL-2025" ], "evidence_note": "PFS benefit ~6.5% absolute at 2 years" }, { "position": "R-CHOP remains acceptable when polatuzumab not accessible", "sources": [ "SRC-NCCN-BCELL-2025" ] } ], "our_default": "R-CHOP for IPI 0-1 OR when polatuzumab not accessible (Ukraine reimbursement gap); Pola-R-CHP for IPI ≥2 with confirmed funding pathway", "rationale": "Polatuzumab not НСЗУ-reimbursed in Ukraine — access is bottleneck. Patient should be informed of trade-off + offered POLARIX-style Pola-R-CHP if funding pathway exists.\n" } ], "do_not_do": [ "Не починати без HBV скринінгу + entecavir prophylaxis при HBsAg+ або anti-HBc+ — ризик фатальної реактивації значно підвищений на anti-CD20.", "Не призначати без baseline LVEF ≥50% — anthracyclines кардіотоксичні; кардіоміопатія часто незворотна.", "Не ігнорувати CNS-IPI — для пацієнтів з ≥4 CNS-IPI або високоризиковими anatomic sites (тестикули, груди, нирки/наднирники, параназальні синуси) додавати CNS prophylaxis (HD-MTX intercalated).", "Не пропускати fertility preservation discussion у репродуктивного віку — циклофосфамід викликає азооспермію + amenorrhea.", "Не вводити вінкристин інтратекально — ФАТАЛЬНО. WHO/FDA вимагають IV mini-bag packaging.", "Не ескалувати дозу при febrile neutropenia без G-CSF — G-CSF prophylaxis для високоризикових пацієнтів (вік >65, prior cytopenia, advanced disease)." ], "do_not_do_en": [ "Do not start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ — risk of fatal reactivation is significantly elevated on anti-CD20.", "Do not prescribe without baseline LVEF ≥50% — anthracyclines are cardiotoxic; cardiomyopathy is often irreversible.", "Do not ignore CNS-IPI — for patients with CNS-IPI ≥4 or high-risk anatomic sites (testicles, breasts, kidneys/adrenals, paranasal sinuses) add CNS prophylaxis (HD-MTX intercalated).", "Do not skip the fertility preservation discussion in patients of reproductive age — cyclophosphamide causes azoospermia + amenorrhea.", "Do not give vincristine intrathecally — FATAL. WHO/FDA require IV mini-bag packaging.", "Do not escalate dose with febrile neutropenia without G-CSF — G-CSF prophylaxis for high-risk patients (age >65, prior cytopenia, advanced disease)." ], "time_critical": false, "last_reviewed": "2026-04-27", "reviewers": [], "reviewer_signoffs": 0, "notes": "STUB — pending Clinical Co-Lead sign-off. Standard track for DLBCL 1L two-plan output (CHARTER §2). For relapsed/refractory after R-CHOP, treatment moves to 2L pathway (salvage chemo → autoSCT for fit; CAR-T for r/r refractory) — separate Indication entities.\n" }, "alternative_indication": { "id": "IND-DLBCL-1L-POLA-R-CHP", "plan_track": "aggressive", "applicable_to": { "disease_id": "DIS-DLBCL-NOS", "line_of_therapy": 1, "stage_requirements": [], "biomarker_requirements_required": [ { "biomarker_id": "BIO-CD20-IHC", "required": true, "value_constraint": "positive (CD20+)" }, { "biomarker_id": "BIO-CD79B-IHC", "required": true, "value_constraint": "positive (CD79b is the polatuzumab vedotin target; expressed in nearly all B-cell lymphomas including DLBCL)" }, { "biomarker_id": "BIO-DLBCL-IPI", "required": true, "value_constraint": "IPI ≥2 — POLARIX PFS benefit driven by higher-risk IPI subset; IPI 0-1 see R-CHOP standard track" }, { "biomarker_id": "BIO-HBV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; HBsAg+ or anti-HBc+ → entecavir prophylaxis mandatory before first rituximab dose; anti-CD20 reactivation risk not reduced by polatuzumab)" }, { "biomarker_id": "BIO-HCV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; anti-HCV+ → reflex BIO-HCV-RNA; coordinate DAA with hepatology)" }, { "biomarker_id": "BIO-HIV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; HIV+ → cART throughout, PJP/MAC prophylaxis if CD4 < 200, CNS prophylaxis regardless of CNS-IPI)" }, { "biomarker_id": "BIO-DLBCL-COO-HANS", "required": false, "value_constraint": "Activated B-cell-like (ABC / non-GCB) showed greater Pola-R-CHP benefit in POLARIX subgroup" }, { "biomarker_id": "BIO-BCL2-EXPRESSION-IHC", "required": false, "value_constraint": "Double-expressor (BCL2-IHC + MYC-IHC) phenotype — Pola-R-CHP may particularly benefit DEL subgroup; rule out HGBL-DH" } ], "biomarker_requirements_excluded": [], "demographic_constraints": { "ecog_max": 2 } }, "recommended_regimen": "REG-POLA-R-CHP", "concurrent_therapy": [], "followed_by": [], "evidence_level": "high", "strength_of_recommendation": "strong", "nccn_category": "1", "expected_outcomes": { "overall_response_rate": "~88% (≥PR after 6 cycles, POLARIX)", "complete_response": "~70%", "progression_free_survival": "2-year PFS ~76.7% (vs 70.2% R-CHOP, HR 0.73)", "overall_survival_5y": "Mature OS data still maturing; trends comparable or favoring Pola-R-CHP" }, "hard_contraindications": [ "CI-HBV-NO-PROPHYLAXIS", "CI-LVEF-LOW-FOR-ANTHRACYCLINE", "CI-BORTEZOMIB-SEVERE-NEUROPATHY" ], "red_flags_triggering_alternative": [], "required_tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT", "TEST-LDH", "TEST-B2-MICROGLOBULIN", "TEST-HBV-SEROLOGY", "TEST-HCV-ANTIBODY", "TEST-HIV-SEROLOGY", "TEST-CD20-IHC", "TEST-PET-CT", "TEST-ECHO", "TEST-LN-EXCISIONAL-BIOPSY", "TEST-FLOW-CYTOMETRY", "TEST-FISH-PANEL", "TEST-PREGNANCY", "TEST-BM-ASPIRATE", "TEST-BM-TREPHINE" ], "desired_tests": [], "rationale": "Aggressive-track default for newly-diagnosed DLBCL NOS with IPI ≥2 (RF-DLBCL-HIGH-IPI fired). Replaces vincristine in R-CHOP with polatuzumab vedotin (anti-CD79b ADC with MMAE payload). POLARIX trial (NEJM 2022) showed ~6.5% absolute PFS improvement at 2 years vs R-CHOP. Toxicity profile comparable; peripheral neuropathy slightly higher with polatuzumab but vincristine removed. Major access constraint in Ukraine: polatuzumab not НСЗУ-reimbursed. Funding pathway (clinical trial / charitable / out-of-pocket) MUST be verified before plan finalized.\n", "rationale_ua": "Поладо-R-CHP (полатузумаб ведотин (polatuzumab vedotin) + ритуксимаб + циклофосфамід + доксорубіцин + преднізолон) є схемою агресивного треку першої лінії (перша лінія) для вперше діагностованої ДВКЛ NOS з IPI >=2 (RF-DLBCL-HIGH-IPI). Замінює вінкристин у R-CHOP на полатузумаб ведотин (anti-CD79b ADC з MMAE-пейлоадом). Дослідження POLARIX (Tilly et al., NEJM 2022; n=879): Pola-R-CHP vs R-CHOP у пацієнтів з IPI 2-5; медіана 2-річного ВБП 76.7% проти 70.2% (HR 0.73, 95% ДІ 0.57-0.95; p=0.02) - абсолютне покращення ~6.5%. Загальна виживаність (ЗВ) подібна між групами. Профіль токсичності порівнянний з R-CHOP; периферична нейропатія дещо вища при полатузумабі, однак вінкристин виключено. NCCN Категорія 1, переважна схема для IPI >=2. Підгрупи: вищий ефект при ABC/non-GCB та double-expressor (DEL) фенотипах. Злиття (fusion/translocation) MYC+BCL2 (double-hit/HGBL-DH) слід виключити (FISH) - HGBL-DH не є показанням Pola-R-CHP за POLARIX. КРИТИЧНО: полатузумаб ведотин не є НСЗУ-відшкодовуваним - шлях фінансування (клінічне дослідження, благодійний, власним коштом) обов'язково верифікувати до затвердження плану.\n", "ukrainian_review_status": "pending_clinical_signoff", "ukrainian_drafted_by": "claude_extraction", "draft_revision": 2, "sources": [ { "source_id": "SRC-POLARIX-TILLY-2022", "position": "supports", "relevant_quote_paraphrase": "Polatuzumab vedotin+R-CHP vs R-CHOP: PFS HR 0.73 (95% CI 0.57–0.95; p=0.02); 2-year PFS 76.7% vs 70.2% (POLARIX)" }, { "source_id": "SRC-NCCN-BCELL-2025", "position": "supports", "relevant_quote_paraphrase": "Pola-R-CHP is a Category 1 preferred regimen for newly-diagnosed DLBCL with IPI ≥2 where polatuzumab is accessible" }, { "source_id": "SRC-ESMO-LYMPHOMA-2025", "position": "supports", "relevant_quote_paraphrase": "ESMO 2024 codifies R-CHOP × 6 as 1L standard for DLBCL NOS; Pola-R-CHP preferred for IPI ≥3 per POLARIX" } ], "known_controversies": [], "do_not_do": [ "Не призначати при відсутності верифікованого funding pathway — daratumumab... вибач, polatuzumab не реімбурсується НСЗУ; пацієнт має бути попереджений ДО запропонування.", "Не починати без HBV скринінгу + entecavir prophylaxis при HBsAg+ або anti-HBc+ — anti-CD20 reactivation ризик не зменшується від polatuzumab.", "Не призначати без baseline LVEF ≥50% — anthracycline cardiotoxicity те ж саме як R-CHOP.", "Не ігнорувати pre-existing peripheral neuropathy — polatuzumab MMAE викликає neuropathy; Grade ≥2 baseline = absolute CI.", "Не пропускати CNS prophylaxis якщо CNS-IPI ≥4 — той же ризик що при R-CHOP.", "Не використовувати при concomitant strong CYP3A4 inhibitor без monitoring — підвищена neuropathy + myelosuppression." ], "do_not_do_en": [ "Do not prescribe without a verified funding pathway — daratumumab... sorry, polatuzumab is not NSZU-reimbursed; the patient must be informed BEFORE being offered.", "Do not start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ — anti-CD20 reactivation risk is not reduced by polatuzumab.", "Do not prescribe without baseline LVEF ≥50% — anthracycline cardiotoxicity is the same as with R-CHOP.", "Do not ignore pre-existing peripheral neuropathy — polatuzumab MMAE causes neuropathy; Grade ≥2 baseline = absolute CI.", "Do not skip CNS prophylaxis if CNS-IPI ≥4 — same risk as with R-CHOP.", "Do not use with concomitant strong CYP3A4 inhibitor without monitoring — increased neuropathy + myelosuppression." ], "time_critical": false, "last_reviewed": "2026-04-27", "reviewers": [], "reviewer_signoffs": 0, "notes": "STUB — pending Clinical Co-Lead sign-off. Aggressive counterpart to IND-DLBCL-1L-RCHOP. Activated by RF-DLBCL-HIGH-IPI; engine routes IPI 0-1 patients to R-CHOP standard track.\n" }, "plan": { "schema_version": null, "id": "PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1", "patient_id": "SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE", "version": 1, "generated_at": "2026-10-18T12:08:55.201302+00:00", "supersedes": null, "superseded_by": null, "revision_trigger": null, "patient_snapshot": { "disease": { "icd_o_3_morphology": "9680/3", "id": "DIS-DLBCL-NOS" }, "line_of_therapy": 1, "biomarkers": { "BIO-CD20-IHC": "positive", "BIO-CD79B-IHC": "positive", "BIO-HBV-STATUS": "positive", "BIO-HCV-STATUS": "negative", "BIO-HIV-STATUS": "negative" }, "demographics": { "age": 54, "sex": "male", "ecog": 1 }, "findings": { "ipi_score": 1, "cns_ipi_score": 1, "anatomic_cns_risk_site": false, "lvef_percent": 62, "biopsy_confirmed": true, "cd20_ihc_status": "positive", "hbsag": "negative", "anti_hbc_total": "positive", "creatinine_clearance_ml_min": 90, "bilirubin_ratio_to_uln": 1, "dlco_percent": 85 }, "patient_id": "SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE", "comment": "Synthetic engineering review probe; not a real patient or a prescription." }, "algorithm_id": "ALGO-DLBCL-1L", "knowledge_base_state": { "loaded_entities": 4273, "medication_selection_withheld": false, "medication_screens": [], "planning_selection_withheld": false, "planning_withholding_reason": null, "histology_selection_withheld": false, "profile_selection_withheld": false, "unconfirmed_profile_fields": [], "indications_used": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "sequencing_indications": [], "algorithm_version": "2026-05-09" }, "tracks": [ { "schema_version": null, "track_id": "standard", "label": "Стандартний план", "label_en": "Standard plan", "indication_id": "IND-DLBCL-1L-RCHOP", "is_default": true, "selection_reason": "Primary current-line option selected by ALGO-DLBCL-1L at step 3; branch-driving red flag: RF-FITNESS-ECOG-FIT.", "indication_data": { "id": "IND-DLBCL-1L-RCHOP", "plan_track": "standard", "applicable_to": { "disease_id": "DIS-DLBCL-NOS", "line_of_therapy": 1, "stage_requirements": [], "biomarker_requirements_required": [ { "biomarker_id": "BIO-CD20-IHC", "required": true, "value_constraint": "positive (CD20+)" }, { "biomarker_id": "BIO-DLBCL-IPI", "required": true, "value_constraint": "IPI 0-5; R-CHOP preferred for IPI 0-1; for IPI ≥2 see Pola-R-CHP" }, { "biomarker_id": "BIO-HBV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; HBsAg+ or anti-HBc+ → entecavir prophylaxis mandatory before first rituximab dose; engine consumes the input to fire RF-UNIVERSAL-HBV-REACTIVATION-RISK)" }, { "biomarker_id": "BIO-HCV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; anti-HCV+ → reflex BIO-HCV-RNA; coordinate DAA with hepatology; does not change R-CHOP regimen choice)" }, { "biomarker_id": "BIO-HIV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; HIV+ → cART throughout, PJP/MAC prophylaxis if CD4 < 200, CNS prophylaxis regardless of CNS-IPI; integrase-inhibitor backbone preferred to avoid ritonavir-vincristine interaction)" }, { "biomarker_id": "BIO-DLBCL-COO-HANS", "required": false, "value_constraint": "GCB or non-GCB by Hans algorithm — non-GCB has worse R-CHOP outcomes; some centres consider R-CHOEP for non-GCB" }, { "biomarker_id": "BIO-BCL2-EXPRESSION-IHC", "required": false, "value_constraint": "BCL2-IHC ≥50% combined with MYC-IHC ≥40% defines double-expressor (DEL) phenotype — poorer prognosis but not an excluder; HGBL-DH (FISH double-hit) must be ruled out" } ], "biomarker_requirements_excluded": [], "demographic_constraints": { "ecog_max": 3 } }, "recommended_regimen": "REG-R-CHOP", "concurrent_therapy": [], "followed_by": [], "evidence_level": "high", "strength_of_recommendation": "strong", "nccn_category": "1", "expected_outcomes": { "overall_response_rate": "~85% (≥PR after 6 cycles)", "complete_response": "~65-70%", "progression_free_survival": "Median PFS ~5 years for low-IPI; ~2 years for high-IPI", "overall_survival_5y": "~60% overall (low-IPI ~80%, high-IPI ~55%)" }, "hard_contraindications": [ "CI-HBV-NO-PROPHYLAXIS", "CI-LVEF-LOW-FOR-ANTHRACYCLINE" ], "red_flags_triggering_alternative": [ "RF-DLBCL-HIGH-IPI" ], "required_tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT", "TEST-LDH", "TEST-B2-MICROGLOBULIN", "TEST-HBV-SEROLOGY", "TEST-HCV-ANTIBODY", "TEST-HIV-SEROLOGY", "TEST-CD20-IHC", "TEST-PET-CT", "TEST-ECHO", "TEST-LN-EXCISIONAL-BIOPSY", "TEST-FLOW-CYTOMETRY", "TEST-FISH-PANEL", "TEST-PREGNANCY", "TEST-BM-ASPIRATE", "TEST-BM-TREPHINE" ], "desired_tests": [], "rationale": "Long-standing 1L standard for newly-diagnosed DLBCL NOS, used for the past 20+ years across NCCN, ESMO, EHA. ~60% overall cure rate; outcomes highly dependent on IPI. Replaced PreCHOP regimens after the rituximab era (RCT data from late 1990s/early 2000s). Default for low-IPI (0-1) patients; for IPI ≥2, modern evidence (POLARIX 2022) favors Pola-R-CHP if accessible (see IND-DLBCL-1L-POLA-R-CHP).\n", "rationale_ua": "R-CHOP (ритуксимаб + циклофосфамід + доксорубіцин + вінкристин + преднізолон) є багаторічним стандартом першої лінії (перша лінія) для вперше діагностованої ДВКЛ NOS, що застосовується понад 20 років в рекомендаціях NCCN, ESMO, EHA. Загальний рівень виліковування ~60%; результати суттєво залежать від IPI. Стандарт вибору для IPI 0-1; при IPI >=2 сучасні дані (POLARIX 2022) свідчать на користь Pola-R-CHP за наявності доступу (div. IND-DLBCL-1L-POLA-R-CHP). NCCN Категорія 1. Схема: ритуксимаб 375 mg/m2 + циклофосфамід 750 mg/m2 + доксорубіцин 50 mg/m2 + вінкристин 1.4 mg/m2 (макс. 2 мг) + преднізолон 100 мг (дні 1-5) q21d x 6 циклів. CNS-профілактика (HD-MTX intercalated) при CNS-IPI >=4 або уражених локалізаціях (тестикули, груди, нирки/наднирники, параназальні синуси). Базовий скринінг HBV обов'язковий; ентекавір при HBsAg+ або anti-HBc+. Базовий ЕХОКГ для LVEF >=50% (антрациклінова кардіотоксичність). Вінкристин вводити ВИКЛЮЧНО внутрішньовенно - інтратекальне введення є ФАТАЛЬНИМ. Рецидивний/рефрактерний (relapsed/refractory) ДВКЛ після R-CHOP потребує переходу на 2L (сальвадж хіміотерапія -> аутоТГСК для придатних; CAR-T для р/р).\n", "ukrainian_review_status": "pending_clinical_signoff", "ukrainian_drafted_by": "claude_extraction", "draft_revision": 2, "sources": [ { "source_id": "SRC-NCCN-BCELL-2025", "position": "supports", "relevant_quote_paraphrase": "R-CHOP is a Category 1 preferred regimen for newly-diagnosed DLBCL across all IPI groups; Pola-R-CHP is preferred Category 1 for IPI ≥2 where accessible" }, { "source_id": "SRC-ESMO-LYMPHOMA-2025", "position": "supports", "relevant_quote_paraphrase": "ESMO 2024 codifies R-CHOP × 6 as 1L standard for DLBCL NOS; Pola-R-CHP preferred for IPI ≥3 per POLARIX" } ], "known_controversies": [ { "topic": "R-CHOP vs Pola-R-CHP for IPI ≥2 1L DLBCL", "positions": [ { "position": "Pola-R-CHP preferred for IPI ≥2 where accessible (POLARIX evidence)", "sources": [ "SRC-NCCN-BCELL-2025" ], "evidence_note": "PFS benefit ~6.5% absolute at 2 years" }, { "position": "R-CHOP remains acceptable when polatuzumab not accessible", "sources": [ "SRC-NCCN-BCELL-2025" ] } ], "our_default": "R-CHOP for IPI 0-1 OR when polatuzumab not accessible (Ukraine reimbursement gap); Pola-R-CHP for IPI ≥2 with confirmed funding pathway", "rationale": "Polatuzumab not НСЗУ-reimbursed in Ukraine — access is bottleneck. Patient should be informed of trade-off + offered POLARIX-style Pola-R-CHP if funding pathway exists.\n" } ], "do_not_do": [ "Не починати без HBV скринінгу + entecavir prophylaxis при HBsAg+ або anti-HBc+ — ризик фатальної реактивації значно підвищений на anti-CD20.", "Не призначати без baseline LVEF ≥50% — anthracyclines кардіотоксичні; кардіоміопатія часто незворотна.", "Не ігнорувати CNS-IPI — для пацієнтів з ≥4 CNS-IPI або високоризиковими anatomic sites (тестикули, груди, нирки/наднирники, параназальні синуси) додавати CNS prophylaxis (HD-MTX intercalated).", "Не пропускати fertility preservation discussion у репродуктивного віку — циклофосфамід викликає азооспермію + amenorrhea.", "Не вводити вінкристин інтратекально — ФАТАЛЬНО. WHO/FDA вимагають IV mini-bag packaging.", "Не ескалувати дозу при febrile neutropenia без G-CSF — G-CSF prophylaxis для високоризикових пацієнтів (вік >65, prior cytopenia, advanced disease)." ], "do_not_do_en": [ "Do not start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ — risk of fatal reactivation is significantly elevated on anti-CD20.", "Do not prescribe without baseline LVEF ≥50% — anthracyclines are cardiotoxic; cardiomyopathy is often irreversible.", "Do not ignore CNS-IPI — for patients with CNS-IPI ≥4 or high-risk anatomic sites (testicles, breasts, kidneys/adrenals, paranasal sinuses) add CNS prophylaxis (HD-MTX intercalated).", "Do not skip the fertility preservation discussion in patients of reproductive age — cyclophosphamide causes azoospermia + amenorrhea.", "Do not give vincristine intrathecally — FATAL. WHO/FDA require IV mini-bag packaging.", "Do not escalate dose with febrile neutropenia without G-CSF — G-CSF prophylaxis for high-risk patients (age >65, prior cytopenia, advanced disease)." ], "time_critical": false, "last_reviewed": "2026-04-27", "reviewers": [], "reviewer_signoffs": 0, "notes": "STUB — pending Clinical Co-Lead sign-off. Standard track for DLBCL 1L two-plan output (CHARTER §2). For relapsed/refractory after R-CHOP, treatment moves to 2L pathway (salvage chemo → autoSCT for fit; CAR-T for r/r refractory) — separate Indication entities.\n" }, "regimen_data": { "id": "REG-R-CHOP", "name": "Rituximab + CHOP (R-CHOP), 6 cycles", "name_ua": "Ритуксимаб + CHOP (R-CHOP), 6 циклів", "alternate_names": [ "R-CHOP", "R-CHOP-21" ], "components": [ { "drug_id": "DRUG-RITUXIMAB", "dose": "375 mg/m²", "schedule": "IV day 1 of each 21-day cycle", "route": "IV" }, { "drug_id": "DRUG-CYCLOPHOSPHAMIDE", "dose": "750 mg/m²", "schedule": "IV day 1 of each 21-day cycle", "route": "IV" }, { "drug_id": "DRUG-DOXORUBICIN", "dose": "50 mg/m²", "schedule": "IV day 1 of each 21-day cycle", "route": "IV" }, { "drug_id": "DRUG-VINCRISTINE", "dose": "1.4 mg/m² (capped at 2 mg total)", "schedule": "IV day 1 of each 21-day cycle", "route": "IV" }, { "drug_id": "DRUG-PREDNISONE", "dose": "100 mg", "schedule": "PO days 1-5 of each 21-day cycle", "route": "PO" } ], "cycle_length_days": 21, "total_cycles": "6 (with consideration of 2-month interim PET-CT after cycles 2-4)", "toxicity_profile": "moderate", "premedication": [ "Antihistamine + acetaminophen + IV steroid before rituximab (especially first dose)", "5-HT3 antagonist + dexamethasone before doxorubicin/cyclophosphamide" ], "mandatory_supportive_care": [ "SUP-PJP-PROPHYLAXIS", "SUP-TLS-PROPHYLAXIS", "SUP-ANTIEMETIC-PREMED" ], "monitoring_schedule_id": "MON-R-CHOP-REGIMEN", "dose_adjustments": [ { "condition": "Cumulative anthracycline approaching 450-500 mg/m² lifetime", "modification": "Echo + LVEF check before next dose; consider regimen change if borderline", "rationale": "Cardiotoxicity is dose-cumulative", "source_refs": [ "SRC-NCCN-BCELL-2025" ] }, { "condition": "Total bilirubin >3 mg/dL", "modification": "Reduce vincristine + doxorubicin per hepatic-impairment dosing", "rationale": "Both are hepatically cleared", "source_refs": [ "SRC-NCCN-BCELL-2025" ] }, { "condition": "Grade ≥2 peripheral neuropathy", "modification": "Hold or reduce vincristine; may convert to non-vincristine regimen", "rationale": "Vincristine neuropathy is dose-cumulative and often permanent" }, { "condition": "ANC <1500 or platelets <100K at cycle start", "modification": "Delay cycle ≥7 days; consider G-CSF support", "rationale": "Cumulative myelosuppression" } ], "ukraine_availability": { "all_components_registered": true, "all_components_reimbursed": true, "notes": "All R-CHOP components reimbursed via НСЗУ for B-cell lymphoma indications" }, "sources": [ "SRC-NCCN-BCELL-2025" ], "between_visit_watchpoints": [ { "trigger_ua": "Помірна втома протягом 3-5 днів після інфузії", "action_ua": "Це нормально — занотуйте, і відпочивайте більше у ці дні. Обговоріть на наступному візиті, якщо втома триває довше", "urgency": "log_at_next_visit", "cycle_day_window": "Day 1-5 of each cycle", "sources": [ "SRC-NCCN-BCELL-2025" ] }, { "trigger_ua": "Випадання волосся (початок на 2-3 тижні після першого циклу)", "action_ua": "Очікуване від доксорубіцину — занотуйте, обговоріть на візиті. Волосся повертається після завершення курсу", "urgency": "log_at_next_visit", "cycle_day_window": "Day 14-21", "sources": [ "SRC-NCCN-BCELL-2025" ] }, { "trigger_ua": "Помірна нудота протягом перших 1-3 днів після циклу", "action_ua": "Приймайте призначені протиблювотні; занотуйте, якщо стають слабшими — обговоріть на наступному візиті", "urgency": "log_at_next_visit", "cycle_day_window": "Day 1-3", "sources": [ "SRC-CTCAE-V5" ] }, { "trigger_ua": "Лихоманка вище 38°C — особливо на 7-14 день циклу", "action_ua": "Подзвоніть у клініку того ж дня — це період можливої низької кількості нейтрофілів і ризику інфекції", "urgency": "call_clinic_same_day", "cycle_day_window": "Day 7-14", "sources": [ "SRC-NCCN-BCELL-2025", "SRC-CTCAE-V5" ] }, { "trigger_ua": "Незвичні синці, кровотеча ясен або носа, що довго не спиняється", "action_ua": "Подзвоніть у клініку того ж дня — це може свідчити про знижену кількість тромбоцитів", "urgency": "call_clinic_same_day", "cycle_day_window": "Day 7-14", "sources": [ "SRC-CTCAE-V5" ] }, { "trigger_ua": "Нова задишка, прискорене серцебиття або біль у грудях", "action_ua": "Подзвоніть у клініку того ж дня — доксорубіцин може впливати на серце; потрібна оцінка", "urgency": "call_clinic_same_day", "sources": [ "SRC-NCCN-BCELL-2025", "SRC-CTCAE-V5" ] }, { "trigger_ua": "Тяжка реакція на інфузію ритуксимабу (особливо першу): задишка, набряк обличчя, висип, тиск падає", "action_ua": "Інфузія зазвичай проводиться в клініці — повідомте медсестру негайно. Якщо реакція виникла вдома, викликайте швидку", "urgency": "er_now", "cycle_day_window": "Day 1 of cycle 1", "sources": [ "SRC-NCCN-BCELL-2025", "SRC-CTCAE-V5" ] }, { "trigger_ua": "Озноб + лихоманка + сплутаність свідомості", "action_ua": "Звертайтесь у лікарню негайно — це ознаки можливого сепсису на тлі низьких нейтрофілів", "urgency": "er_now", "sources": [ "SRC-CTCAE-V5" ] } ], "last_reviewed": "2026-04-25", "notes": "Standard 1L regimen for newly-diagnosed DLBCL NOS for the past 20+ years. ~60% cure rate overall, ~80% for low-IPI / ~55% for high-IPI. HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ MANDATORY before first rituximab dose. Echocardiogram (LVEF) baseline + after cumulative dose >300 mg/m². Interim PET-CT after cycles 2-4 helpful for response assessment but doesn't routinely change therapy unless PD seen.\n", "notes_ua": "стандарт 1L схема for newly-diagnosed DLBCL NOS for the past 20+ years. ~60% cure rate overall, ~80% for low-IPI / ~55% for high-IPI. HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ обов'язковий before first ритуксимаб доза. Echocardiogram (LVEF) базове + after cumulative доза >300 mg/m². Interim PET-CT after цикли 2-4 helpful for відповідь assessment but doesn't routinely change терапія unless PD seen.\n", "ukrainian_review_status": "pending_clinical_signoff", "ukrainian_drafted_by": "claude_extraction" }, "monitoring_data": { "id": "MON-R-CHOP-REGIMEN", "linked_to_regimen": "REG-R-CHOP", "phases": [ { "name": "baseline", "window": "Within 2 weeks before cycle 1", "window_ua": "Протягом 2 тижнів до циклу 1", "tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT", "TEST-LDH", "TEST-B2-MICROGLOBULIN", "TEST-HBV-SEROLOGY", "TEST-HCV-ANTIBODY", "TEST-HIV-SEROLOGY", "TEST-PET-CT", "TEST-LN-EXCISIONAL-BIOPSY", "TEST-FLOW-CYTOMETRY", "TEST-CD20-IHC", "TEST-ECHO", "TEST-PREGNANCY", "TEST-BM-ASPIRATE", "TEST-BM-TREPHINE" ], "visits": [ "Treatment planning visit with hematology + cardiology + ID + reproductive counseling" ], "checkpoints": [ "Confirm CD20+ DLBCL histology; rule out double-hit (FISH for MYC/BCL2/BCL6)", "Confirm HBV status + entecavir prophylaxis plan if HBsAg+ or anti-HBc+", "Baseline LVEF ≥50% before doxorubicin", "IPI calculation documented (age, ECOG, LDH, stage, extranodal sites)", "CNS-IPI calculation if anatomic risk sites or composite score concerning", "Fertility preservation discussion (sperm banking / oocyte cryo) for childbearing-age" ], "checkpoints_ua": [ "Підтвердити CD20+ DLBCL гістологію; виключити double-hit (FISH на MYC/BCL2/BCL6)", "Підтвердити статус HBV + план профілактики ентекавіром при HBsAg+ або anti-HBc+", "Базовий LVEF ≥50% перед доксорубіцином", "Документувати розрахунок IPI (вік, ECOG, LDH, стадія, екстранодальні локалізації)", "Розрахунок CNS-IPI при анатомічних зонах ризику або тривожному загальному балі", "Обговорення збереження фертильності (банкінг сперми / кріоконсервація ооцитів) для пацієнтів дітородного віку" ] }, { "name": "on_treatment", "window": "Day 1 of every 21-day cycle", "window_ua": "День 1 кожного 21-денного циклу", "tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT" ], "visits": [ "Pre-cycle clinical assessment + infusion-day labs + neuropathy screen" ], "checkpoints": [ "ANC ≥1500 + platelets ≥100K before each cycle (delay or G-CSF if not)", "Neuropathy grade documented (CTCAE) — vincristine modification if ≥2", "LVEF re-check after cumulative doxorubicin ~300 mg/m²" ], "checkpoints_ua": [ "ANC ≥1500 + тромбоцити ≥100 тис. перед кожним циклом (інакше — відстрочка або G-CSF)", "Ступінь нейропатії документується (CTCAE) — модифікація вінкристину при ≥2", "Повторна оцінка LVEF після кумулятивної дози доксорубіцину ~300 мг/м²" ] }, { "name": "interim_response_assessment", "window": "After cycles 2-4 (interim PET-CT)", "window_ua": "Після циклів 2–4 (проміжне PET-CT)", "tests": [ "TEST-PET-CT", "TEST-LDH" ], "visits": [ "Restaging visit" ], "checkpoints": [ "Lugano response criteria + Deauville score", "If Deauville 4-5 with mass progression → consider salvage or trial" ], "checkpoints_ua": [ "Критерії відповіді за Lugano + бал за Deauville", "При Deauville 4–5 з прогресуванням маси → розглянути salvage-терапію або клінічне дослідження" ] }, { "name": "end_of_treatment", "window": "After cycle 6 (within 6-8 weeks)", "window_ua": "Після циклу 6 (протягом 6–8 тижнів)", "tests": [ "TEST-PET-CT", "TEST-CBC", "TEST-CMP", "TEST-LDH" ], "visits": [ "End-of-treatment restaging + survivorship transition" ], "checkpoints": [ "Confirm CR vs PR vs SD vs PD by Lugano/Deauville", "Begin survivorship plan: cardiac surveillance schedule, vaccination catch-up, second-cancer screening" ], "checkpoints_ua": [ "Підтвердити CR / PR / SD / PD за Lugano/Deauville", "Початок плану survivorship: графік кардіологічного спостереження, надолуження вакцинації, скринінг другого раку" ] }, { "name": "follow_up_short", "window": "Every 3 months × 2 years post-treatment", "window_ua": "Кожні 3 місяці протягом 2 років після лікування", "tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT", "TEST-LDH" ], "visits": [ "Clinical assessment + labs" ], "checkpoints": [ "Surveillance for relapse (~40% relapse risk by 2 years overall)", "HBV reactivation monitoring continues for 12 months post anti-CD20" ], "checkpoints_ua": [ "Спостереження щодо рецидиву (загальний ризик рецидиву ~40% протягом 2 років)", "Моніторинг реактивації HBV триває 12 місяців після anti-CD20" ] }, { "name": "follow_up_long", "window": "Every 6 months years 3-5, then annually", "window_ua": "Кожні 6 місяців у роки 3–5, потім щорічно", "tests": [ "TEST-CBC", "TEST-LFT", "TEST-ECHO" ], "visits": [ "Clinical + cardiac surveillance" ], "checkpoints": [ "Late cardiomyopathy screening (LVEF) annually if cumulative dox >300", "Annual second-malignancy screening (skin, breast, etc. age-appropriate)" ], "checkpoints_ua": [ "Щорічний скринінг пізньої кардіоміопатії (LVEF) при кумулятивній дозі доксорубіцину >300", "Щорічний скринінг другої злоякісної пухлини (шкіра, молочна залоза тощо — відповідно до віку)" ] } ], "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25", "machine_translated_review_pending": true, "notes": "Shared by REG-R-CHOP and REG-POLA-R-CHP (Pola-R-CHP differs only in cycle composition; monitoring is identical). HBV-DNA quarterly for duration of therapy and 12 months post if anti-CD20 used. UA translations of window / checkpoints added 2026-05-19 under CHARTER §8.3 dev-mode exemption; awaiting Clinical Co-Lead sign-off.\n" }, "supportive_care_data": [ { "id": "SUP-PJP-PROPHYLAXIS", "intervention_type": "prophylaxis", "name": "Pneumocystis jirovecii prophylaxis", "name_ua": "Профілактика пневмоцистної пневмонії", "standard_intervention": { "drug_id": "DRUG-TMP-SMX", "dose": "160/800 mg PO 3x/week (Mon/Wed/Fri)", "schedule": "Start with first cycle of chemoimmunotherapy; continue ≥6 months after last anti-CD20 dose", "notes": "Alternative: dapsone 100 mg PO daily if sulfa allergy (verify G6PD status first)" }, "triggers": { "relevant_regimens": [ "REG-BR-STANDARD" ], "clinical_condition": "Sustained immunosuppression from rituximab + chemotherapy" }, "rationale": "Anti-CD20 therapy combined with cytotoxic chemotherapy substantially prolongs B-cell depletion and increases PJP risk for months after completion of treatment.\n", "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25" }, { "id": "SUP-TLS-PROPHYLAXIS", "intervention_type": "prophylaxis", "name": "Tumor lysis syndrome prophylaxis", "name_ua": "Профілактика синдрому лізису пухлини", "standard_intervention": { "drug_id": "DRUG-ALLOPURINOL", "dose": "300 mg PO daily", "schedule": "Start 24-48h before chemotherapy; continue 5-7 days", "notes": "Plus IV hydration 2-3 L/m²/day" }, "triggers": { "relevant_regimens": [ "REG-BR-STANDARD" ], "clinical_condition": "High tumor burden: bulky disease (>=7 cm), elevated LDH, or rapid clinical progression" }, "rationale": "TLS risk is moderate-to-high in bulky indolent lymphoma starting cytoreductive therapy. Prophylaxis with allopurinol + hydration reduces hyperuricemia and downstream renal injury.\n", "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25" }, { "id": "SUP-ANTIEMETIC-PREMED", "intervention_type": "premedication", "name": "Antiemetic premedication for moderately emetogenic chemotherapy", "name_ua": "Антиеметична премедикація", "standard_intervention": { "drug_id": "DRUG-ONDANSETRON", "dose": "8 mg IV", "schedule": "30 minutes before chemotherapy; then 8 mg PO q8h × 24-48h", "notes": "Add dexamethasone 8-12 mg IV for higher emetogenicity" }, "triggers": { "relevant_regimens": [ "REG-BR-STANDARD" ] }, "rationale": "Bendamustine is moderately emetogenic; standard 5-HT3 antagonist prevents acute and delayed nausea/vomiting.\n", "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25" } ], "contraindications_data": [ { "id": "CI-HBV-NO-PROPHYLAXIS", "severity": "absolute", "trigger": { "type": "patient_condition", "conditions": [ { "patient_condition": "HBsAg+ OR anti-HBc+" }, { "patient_condition": "no concurrent HBV antiviral prophylaxis prescribed" } ], "logic": "AND" }, "description": "Active or latent HBV without antiviral prophylaxis is an absolute contraindication to starting B-cell-depleting / immunomodulatory monoclonal antibody therapy (anti-CD20, anti-CD30 ADC, anti-CD38). Severe HBV reactivation hepatitis risk including fulminant hepatic failure.", "description_ua": "Активний або латентний HBV без противірусної профілактики — абсолютне протипоказання до моноклональних антитіл, що вичерпують B-клітини або імуномодулюючих (anti-CD20, anti-CD30 ADC, anti-CD38)", "alternative_actions": [ "Start entecavir 0.5 mg PO daily (or tenofovir) — SUP-HBV-PROPHYLAXIS — before first dose", "Refer to hepatologist for shared management; HBV-DNA q-cycle monitoring", "Defer therapy until prophylaxis confirmed and first dose of antiviral administered", "Continue antiviral ≥12 months after last dose of immunosuppressive antibody" ], "affects_indications": [], "affects_drugs": [ "DRUG-RITUXIMAB", "DRUG-OBINUTUZUMAB", "DRUG-BRENTUXIMAB-VEDOTIN", "DRUG-DARATUMUMAB" ], "affects_regimens": [ "REG-BR-STANDARD" ], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-EASL-HCV-2023", "SRC-NCCN-MM-2025" ], "last_reviewed": "2026-04-27", "notes": "Triggered by RF-HBV-COINFECTION / RF-UNIVERSAL-HBV-REACTIVATION-RISK; resolved by adding SUP-HBV-PROPHYLAXIS to plan. Extended 2026-04-27 to cover anti-CD30 ADC (brentuximab vedotin) used in CHL A+AVD and anti-CD38 mAbs (daratumumab, isatuximab) used in MM regimens — both classes have documented HBV reactivation risk per their FDA labels and NCCN guidelines.\n" }, { "id": "CI-LVEF-LOW-FOR-ANTHRACYCLINE", "severity": "absolute", "trigger": { "type": "lab_result", "conditions": [ { "patient_condition": "Baseline LVEF <50% by echocardiogram or MUGA" } ], "logic": "AND" }, "description": "Pre-treatment LVEF <50% is an absolute contraindication to anthracycline-containing regimens (R-CHOP, Pola-R-CHP, ABVD, BV-AVD, etc.). Cardiotoxicity from doxorubicin is dose-cumulative and often irreversible; starting with already-impaired function risks acute decompensation.", "description_ua": "LVEF <50% на baseline — абсолютне протипоказання до anthracycline-вмісних регімів (R-CHOP, Pola-R-CHP, ABVD, BV-AVD). Кардіотоксичність доксорубіцину доза-кумулятивна і часто незворотна.", "alternative_actions": [ "Cardiology consult — confirm LVEF + assess reversible causes (treat HTN, ischemia, etc.)", "Consider non-anthracycline regimen: R-CEOP (etoposide replaces doxorubicin), R-mini-CHOP for elderly, R-bendamustine for selected patients", "Liposomal doxorubicin in selected cases (lower cardiotoxicity per dose)", "Dexrazoxane cardioprotectant if anthracycline absolutely required" ], "affects_indications": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "affects_drugs": [ "DRUG-DOXORUBICIN" ], "affects_regimens": [ "REG-R-CHOP", "REG-POLA-R-CHP" ], "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25", "notes": "Cumulative anthracycline lifetime threshold ~450-500 mg/m² doxorubicin. Borderline LVEF (50-55%) — proceed with serial echo monitoring. Trastuzumab + anthracycline combination separately contraindicated (additive cardiotoxicity).\n" } ] }, { "schema_version": null, "track_id": "aggressive", "label": "Агресивний план", "label_en": "Aggressive plan", "indication_id": "IND-DLBCL-1L-POLA-R-CHP", "is_default": false, "selection_reason": "Current-line alternative presented for HCP consideration", "indication_data": { "id": "IND-DLBCL-1L-POLA-R-CHP", "plan_track": "aggressive", "applicable_to": { "disease_id": "DIS-DLBCL-NOS", "line_of_therapy": 1, "stage_requirements": [], "biomarker_requirements_required": [ { "biomarker_id": "BIO-CD20-IHC", "required": true, "value_constraint": "positive (CD20+)" }, { "biomarker_id": "BIO-CD79B-IHC", "required": true, "value_constraint": "positive (CD79b is the polatuzumab vedotin target; expressed in nearly all B-cell lymphomas including DLBCL)" }, { "biomarker_id": "BIO-DLBCL-IPI", "required": true, "value_constraint": "IPI ≥2 — POLARIX PFS benefit driven by higher-risk IPI subset; IPI 0-1 see R-CHOP standard track" }, { "biomarker_id": "BIO-HBV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; HBsAg+ or anti-HBc+ → entecavir prophylaxis mandatory before first rituximab dose; anti-CD20 reactivation risk not reduced by polatuzumab)" }, { "biomarker_id": "BIO-HCV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; anti-HCV+ → reflex BIO-HCV-RNA; coordinate DAA with hepatology)" }, { "biomarker_id": "BIO-HIV-STATUS", "required": true, "value_constraint": "any value valid (categorical etiology gate; HIV+ → cART throughout, PJP/MAC prophylaxis if CD4 < 200, CNS prophylaxis regardless of CNS-IPI)" }, { "biomarker_id": "BIO-DLBCL-COO-HANS", "required": false, "value_constraint": "Activated B-cell-like (ABC / non-GCB) showed greater Pola-R-CHP benefit in POLARIX subgroup" }, { "biomarker_id": "BIO-BCL2-EXPRESSION-IHC", "required": false, "value_constraint": "Double-expressor (BCL2-IHC + MYC-IHC) phenotype — Pola-R-CHP may particularly benefit DEL subgroup; rule out HGBL-DH" } ], "biomarker_requirements_excluded": [], "demographic_constraints": { "ecog_max": 2 } }, "recommended_regimen": "REG-POLA-R-CHP", "concurrent_therapy": [], "followed_by": [], "evidence_level": "high", "strength_of_recommendation": "strong", "nccn_category": "1", "expected_outcomes": { "overall_response_rate": "~88% (≥PR after 6 cycles, POLARIX)", "complete_response": "~70%", "progression_free_survival": "2-year PFS ~76.7% (vs 70.2% R-CHOP, HR 0.73)", "overall_survival_5y": "Mature OS data still maturing; trends comparable or favoring Pola-R-CHP" }, "hard_contraindications": [ "CI-HBV-NO-PROPHYLAXIS", "CI-LVEF-LOW-FOR-ANTHRACYCLINE", "CI-BORTEZOMIB-SEVERE-NEUROPATHY" ], "red_flags_triggering_alternative": [], "required_tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT", "TEST-LDH", "TEST-B2-MICROGLOBULIN", "TEST-HBV-SEROLOGY", "TEST-HCV-ANTIBODY", "TEST-HIV-SEROLOGY", "TEST-CD20-IHC", "TEST-PET-CT", "TEST-ECHO", "TEST-LN-EXCISIONAL-BIOPSY", "TEST-FLOW-CYTOMETRY", "TEST-FISH-PANEL", "TEST-PREGNANCY", "TEST-BM-ASPIRATE", "TEST-BM-TREPHINE" ], "desired_tests": [], "rationale": "Aggressive-track default for newly-diagnosed DLBCL NOS with IPI ≥2 (RF-DLBCL-HIGH-IPI fired). Replaces vincristine in R-CHOP with polatuzumab vedotin (anti-CD79b ADC with MMAE payload). POLARIX trial (NEJM 2022) showed ~6.5% absolute PFS improvement at 2 years vs R-CHOP. Toxicity profile comparable; peripheral neuropathy slightly higher with polatuzumab but vincristine removed. Major access constraint in Ukraine: polatuzumab not НСЗУ-reimbursed. Funding pathway (clinical trial / charitable / out-of-pocket) MUST be verified before plan finalized.\n", "rationale_ua": "Поладо-R-CHP (полатузумаб ведотин (polatuzumab vedotin) + ритуксимаб + циклофосфамід + доксорубіцин + преднізолон) є схемою агресивного треку першої лінії (перша лінія) для вперше діагностованої ДВКЛ NOS з IPI >=2 (RF-DLBCL-HIGH-IPI). Замінює вінкристин у R-CHOP на полатузумаб ведотин (anti-CD79b ADC з MMAE-пейлоадом). Дослідження POLARIX (Tilly et al., NEJM 2022; n=879): Pola-R-CHP vs R-CHOP у пацієнтів з IPI 2-5; медіана 2-річного ВБП 76.7% проти 70.2% (HR 0.73, 95% ДІ 0.57-0.95; p=0.02) - абсолютне покращення ~6.5%. Загальна виживаність (ЗВ) подібна між групами. Профіль токсичності порівнянний з R-CHOP; периферична нейропатія дещо вища при полатузумабі, однак вінкристин виключено. NCCN Категорія 1, переважна схема для IPI >=2. Підгрупи: вищий ефект при ABC/non-GCB та double-expressor (DEL) фенотипах. Злиття (fusion/translocation) MYC+BCL2 (double-hit/HGBL-DH) слід виключити (FISH) - HGBL-DH не є показанням Pola-R-CHP за POLARIX. КРИТИЧНО: полатузумаб ведотин не є НСЗУ-відшкодовуваним - шлях фінансування (клінічне дослідження, благодійний, власним коштом) обов'язково верифікувати до затвердження плану.\n", "ukrainian_review_status": "pending_clinical_signoff", "ukrainian_drafted_by": "claude_extraction", "draft_revision": 2, "sources": [ { "source_id": "SRC-POLARIX-TILLY-2022", "position": "supports", "relevant_quote_paraphrase": "Polatuzumab vedotin+R-CHP vs R-CHOP: PFS HR 0.73 (95% CI 0.57–0.95; p=0.02); 2-year PFS 76.7% vs 70.2% (POLARIX)" }, { "source_id": "SRC-NCCN-BCELL-2025", "position": "supports", "relevant_quote_paraphrase": "Pola-R-CHP is a Category 1 preferred regimen for newly-diagnosed DLBCL with IPI ≥2 where polatuzumab is accessible" }, { "source_id": "SRC-ESMO-LYMPHOMA-2025", "position": "supports", "relevant_quote_paraphrase": "ESMO 2024 codifies R-CHOP × 6 as 1L standard for DLBCL NOS; Pola-R-CHP preferred for IPI ≥3 per POLARIX" } ], "known_controversies": [], "do_not_do": [ "Не призначати при відсутності верифікованого funding pathway — daratumumab... вибач, polatuzumab не реімбурсується НСЗУ; пацієнт має бути попереджений ДО запропонування.", "Не починати без HBV скринінгу + entecavir prophylaxis при HBsAg+ або anti-HBc+ — anti-CD20 reactivation ризик не зменшується від polatuzumab.", "Не призначати без baseline LVEF ≥50% — anthracycline cardiotoxicity те ж саме як R-CHOP.", "Не ігнорувати pre-existing peripheral neuropathy — polatuzumab MMAE викликає neuropathy; Grade ≥2 baseline = absolute CI.", "Не пропускати CNS prophylaxis якщо CNS-IPI ≥4 — той же ризик що при R-CHOP.", "Не використовувати при concomitant strong CYP3A4 inhibitor без monitoring — підвищена neuropathy + myelosuppression." ], "do_not_do_en": [ "Do not prescribe without a verified funding pathway — daratumumab... sorry, polatuzumab is not NSZU-reimbursed; the patient must be informed BEFORE being offered.", "Do not start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ — anti-CD20 reactivation risk is not reduced by polatuzumab.", "Do not prescribe without baseline LVEF ≥50% — anthracycline cardiotoxicity is the same as with R-CHOP.", "Do not ignore pre-existing peripheral neuropathy — polatuzumab MMAE causes neuropathy; Grade ≥2 baseline = absolute CI.", "Do not skip CNS prophylaxis if CNS-IPI ≥4 — same risk as with R-CHOP.", "Do not use with concomitant strong CYP3A4 inhibitor without monitoring — increased neuropathy + myelosuppression." ], "time_critical": false, "last_reviewed": "2026-04-27", "reviewers": [], "reviewer_signoffs": 0, "notes": "STUB — pending Clinical Co-Lead sign-off. Aggressive counterpart to IND-DLBCL-1L-RCHOP. Activated by RF-DLBCL-HIGH-IPI; engine routes IPI 0-1 patients to R-CHOP standard track.\n" }, "regimen_data": { "id": "REG-POLA-R-CHP", "name": "Polatuzumab vedotin + Rituximab + CHP (Pola-R-CHP), 6 cycles + 2× rituximab", "name_ua": "Полатузумаб ведотин + Ритуксимаб + CHP (Pola-R-CHP), 6 циклів + 2× ритуксимаб", "alternate_names": [ "Pola-R-CHP", "POLARIX-style" ], "components": [ { "drug_id": "DRUG-POLATUZUMAB-VEDOTIN", "dose": "1.8 mg/kg", "schedule": "IV day 1 of each 21-day cycle, cycles 1-6", "route": "IV" }, { "drug_id": "DRUG-RITUXIMAB", "dose": "375 mg/m²", "schedule": "IV day 1 of each 21-day cycle, cycles 1-8 (last 2 cycles rituximab-only)", "route": "IV" }, { "drug_id": "DRUG-CYCLOPHOSPHAMIDE", "dose": "750 mg/m²", "schedule": "IV day 1 of each 21-day cycle, cycles 1-6", "route": "IV" }, { "drug_id": "DRUG-DOXORUBICIN", "dose": "50 mg/m²", "schedule": "IV day 1 of each 21-day cycle, cycles 1-6", "route": "IV" }, { "drug_id": "DRUG-PREDNISONE", "dose": "100 mg", "schedule": "PO days 1-5 of each 21-day cycle, cycles 1-6", "route": "PO" } ], "cycle_length_days": 21, "total_cycles": "6 (Pola-R-CHP) + 2× rituximab consolidation (cycles 7-8)", "toxicity_profile": "moderate-high", "premedication": [ "Antihistamine + acetaminophen before polatuzumab (first dose)", "Antihistamine + acetaminophen + IV steroid before rituximab (especially first dose)", "5-HT3 antagonist + dexamethasone before chemotherapy" ], "mandatory_supportive_care": [ "SUP-PJP-PROPHYLAXIS", "SUP-TLS-PROPHYLAXIS", "SUP-ANTIEMETIC-PREMED" ], "monitoring_schedule_id": "MON-R-CHOP-REGIMEN", "dose_adjustments": [ { "condition": "Grade ≥2 peripheral neuropathy", "modification": "Hold polatuzumab; consider switching to vincristine (R-CHOP)", "rationale": "Polatuzumab carries dose-limiting neuropathy from MMAE payload", "source_refs": [ "SRC-NCCN-BCELL-2025" ] }, { "condition": "Cumulative anthracycline >450-500 mg/m²", "modification": "Echo + LVEF check before next dose; consider regimen change", "rationale": "Cardiotoxicity is dose-cumulative", "source_refs": [ "SRC-NCCN-BCELL-2025" ] }, { "condition": "Strong CYP3A4 inhibitor concomitant", "modification": "Avoid coadministration if possible; if necessary, monitor for increased neuropathy/myelosuppression", "rationale": "Polatuzumab MMAE is CYP3A4 substrate" } ], "ukraine_availability": { "all_components_registered": false, "all_components_reimbursed": false, "notes": "Polatuzumab vedotin is NOT registered/reimbursed in Ukraine as of 2026-04-25 — clinical trial enrollment, charitable scheme, or out-of-pocket are the only access pathways. This is a meaningful barrier; flag explicitly to patient before regimen offered.\n" }, "sources": [ "SRC-NCCN-BCELL-2025" ], "between_visit_watchpoints": [ { "trigger_ua": "Поколювання або оніміння в кистях/стопах", "action_ua": "Полатузумаб може спричиняти нейропатію (менше, ніж вінкристин) — занотовуйте", "urgency": "log_at_next_visit", "sources": [ "SRC-NCCN-BCELL-2025" ] }, { "trigger_ua": "Помірна втома, випадання волосся", "action_ua": "Очікувано — повертається після курсу", "urgency": "log_at_next_visit", "sources": [ "SRC-NCCN-BCELL-2025" ] }, { "trigger_ua": "Помірна нудота", "action_ua": "Приймайте призначені протиблювотні", "urgency": "log_at_next_visit", "cycle_day_window": "Day 1-3", "sources": [ "SRC-CTCAE-V5" ] }, { "trigger_ua": "Лихоманка вище 38°C", "action_ua": "Подзвоніть у клініку того ж дня — потрібен контроль показників крові", "urgency": "call_clinic_same_day", "cycle_day_window": "Day 7-14", "sources": [ "SRC-NCCN-BCELL-2025", "SRC-CTCAE-V5" ] }, { "trigger_ua": "Поколювання стає сильним болем", "action_ua": "Подзвоніть у клініку того ж дня — потрібна корекція дози полатузумабу", "urgency": "call_clinic_same_day", "sources": [ "SRC-NCCN-BCELL-2025" ] }, { "trigger_ua": "Нова задишка, прискорене серцебиття, набряки ніг", "action_ua": "Подзвоніть у клініку того ж дня — доксорубіцин впливає на серце", "urgency": "call_clinic_same_day", "sources": [ "SRC-NCCN-BCELL-2025" ] }, { "trigger_ua": "Тяжка реакція на інфузію ритуксимабу або полатузумабу", "action_ua": "Інфузія в клініці — медперсонал реагує негайно", "urgency": "er_now", "cycle_day_window": "Day 1 of cycle 1", "sources": [ "SRC-NCCN-BCELL-2025" ] } ], "last_reviewed": "2026-04-25", "notes": "POLARIX trial (NEJM 2022): in IPI ≥2 newly-diagnosed DLBCL, superior 2-year PFS (76.7% vs 70.2% R-CHOP, HR 0.73). Comparable OS (mature data still maturing) and toxicity profile (more PN with polatuzumab but offset by NO vincristine). Becoming the new 1L standard for IPI ≥2 in resourced settings — access in Ukraine is the bottleneck. Vincristine is replaced by polatuzumab (hence \"CHP\" not \"CHOP\").\n", "notes_ua": "POLARIX дослідження (NEJM 2022): in IPI ≥2 newly-diagnosed DLBCL, перевершує 2-year PFS (76.7% проти 70.2% R-CHOP, HR 0.73). співставний OS (mature дані still maturing) and профіль токсичності (more PN with polatuzumab but offset by ні вінкристин). Becoming the new 1L стандарт for IPI ≥2 in resourced settings — access in Ukraine is the bottleneck. вінкристин is replaced by polatuzumab (hence \"CHP\" not \"CHOP\").\n", "ukrainian_review_status": "pending_clinical_signoff", "ukrainian_drafted_by": "claude_extraction" }, "monitoring_data": { "id": "MON-R-CHOP-REGIMEN", "linked_to_regimen": "REG-R-CHOP", "phases": [ { "name": "baseline", "window": "Within 2 weeks before cycle 1", "window_ua": "Протягом 2 тижнів до циклу 1", "tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT", "TEST-LDH", "TEST-B2-MICROGLOBULIN", "TEST-HBV-SEROLOGY", "TEST-HCV-ANTIBODY", "TEST-HIV-SEROLOGY", "TEST-PET-CT", "TEST-LN-EXCISIONAL-BIOPSY", "TEST-FLOW-CYTOMETRY", "TEST-CD20-IHC", "TEST-ECHO", "TEST-PREGNANCY", "TEST-BM-ASPIRATE", "TEST-BM-TREPHINE" ], "visits": [ "Treatment planning visit with hematology + cardiology + ID + reproductive counseling" ], "checkpoints": [ "Confirm CD20+ DLBCL histology; rule out double-hit (FISH for MYC/BCL2/BCL6)", "Confirm HBV status + entecavir prophylaxis plan if HBsAg+ or anti-HBc+", "Baseline LVEF ≥50% before doxorubicin", "IPI calculation documented (age, ECOG, LDH, stage, extranodal sites)", "CNS-IPI calculation if anatomic risk sites or composite score concerning", "Fertility preservation discussion (sperm banking / oocyte cryo) for childbearing-age" ], "checkpoints_ua": [ "Підтвердити CD20+ DLBCL гістологію; виключити double-hit (FISH на MYC/BCL2/BCL6)", "Підтвердити статус HBV + план профілактики ентекавіром при HBsAg+ або anti-HBc+", "Базовий LVEF ≥50% перед доксорубіцином", "Документувати розрахунок IPI (вік, ECOG, LDH, стадія, екстранодальні локалізації)", "Розрахунок CNS-IPI при анатомічних зонах ризику або тривожному загальному балі", "Обговорення збереження фертильності (банкінг сперми / кріоконсервація ооцитів) для пацієнтів дітородного віку" ] }, { "name": "on_treatment", "window": "Day 1 of every 21-day cycle", "window_ua": "День 1 кожного 21-денного циклу", "tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT" ], "visits": [ "Pre-cycle clinical assessment + infusion-day labs + neuropathy screen" ], "checkpoints": [ "ANC ≥1500 + platelets ≥100K before each cycle (delay or G-CSF if not)", "Neuropathy grade documented (CTCAE) — vincristine modification if ≥2", "LVEF re-check after cumulative doxorubicin ~300 mg/m²" ], "checkpoints_ua": [ "ANC ≥1500 + тромбоцити ≥100 тис. перед кожним циклом (інакше — відстрочка або G-CSF)", "Ступінь нейропатії документується (CTCAE) — модифікація вінкристину при ≥2", "Повторна оцінка LVEF після кумулятивної дози доксорубіцину ~300 мг/м²" ] }, { "name": "interim_response_assessment", "window": "After cycles 2-4 (interim PET-CT)", "window_ua": "Після циклів 2–4 (проміжне PET-CT)", "tests": [ "TEST-PET-CT", "TEST-LDH" ], "visits": [ "Restaging visit" ], "checkpoints": [ "Lugano response criteria + Deauville score", "If Deauville 4-5 with mass progression → consider salvage or trial" ], "checkpoints_ua": [ "Критерії відповіді за Lugano + бал за Deauville", "При Deauville 4–5 з прогресуванням маси → розглянути salvage-терапію або клінічне дослідження" ] }, { "name": "end_of_treatment", "window": "After cycle 6 (within 6-8 weeks)", "window_ua": "Після циклу 6 (протягом 6–8 тижнів)", "tests": [ "TEST-PET-CT", "TEST-CBC", "TEST-CMP", "TEST-LDH" ], "visits": [ "End-of-treatment restaging + survivorship transition" ], "checkpoints": [ "Confirm CR vs PR vs SD vs PD by Lugano/Deauville", "Begin survivorship plan: cardiac surveillance schedule, vaccination catch-up, second-cancer screening" ], "checkpoints_ua": [ "Підтвердити CR / PR / SD / PD за Lugano/Deauville", "Початок плану survivorship: графік кардіологічного спостереження, надолуження вакцинації, скринінг другого раку" ] }, { "name": "follow_up_short", "window": "Every 3 months × 2 years post-treatment", "window_ua": "Кожні 3 місяці протягом 2 років після лікування", "tests": [ "TEST-CBC", "TEST-CMP", "TEST-LFT", "TEST-LDH" ], "visits": [ "Clinical assessment + labs" ], "checkpoints": [ "Surveillance for relapse (~40% relapse risk by 2 years overall)", "HBV reactivation monitoring continues for 12 months post anti-CD20" ], "checkpoints_ua": [ "Спостереження щодо рецидиву (загальний ризик рецидиву ~40% протягом 2 років)", "Моніторинг реактивації HBV триває 12 місяців після anti-CD20" ] }, { "name": "follow_up_long", "window": "Every 6 months years 3-5, then annually", "window_ua": "Кожні 6 місяців у роки 3–5, потім щорічно", "tests": [ "TEST-CBC", "TEST-LFT", "TEST-ECHO" ], "visits": [ "Clinical + cardiac surveillance" ], "checkpoints": [ "Late cardiomyopathy screening (LVEF) annually if cumulative dox >300", "Annual second-malignancy screening (skin, breast, etc. age-appropriate)" ], "checkpoints_ua": [ "Щорічний скринінг пізньої кардіоміопатії (LVEF) при кумулятивній дозі доксорубіцину >300", "Щорічний скринінг другої злоякісної пухлини (шкіра, молочна залоза тощо — відповідно до віку)" ] } ], "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25", "machine_translated_review_pending": true, "notes": "Shared by REG-R-CHOP and REG-POLA-R-CHP (Pola-R-CHP differs only in cycle composition; monitoring is identical). HBV-DNA quarterly for duration of therapy and 12 months post if anti-CD20 used. UA translations of window / checkpoints added 2026-05-19 under CHARTER §8.3 dev-mode exemption; awaiting Clinical Co-Lead sign-off.\n" }, "supportive_care_data": [ { "id": "SUP-PJP-PROPHYLAXIS", "intervention_type": "prophylaxis", "name": "Pneumocystis jirovecii prophylaxis", "name_ua": "Профілактика пневмоцистної пневмонії", "standard_intervention": { "drug_id": "DRUG-TMP-SMX", "dose": "160/800 mg PO 3x/week (Mon/Wed/Fri)", "schedule": "Start with first cycle of chemoimmunotherapy; continue ≥6 months after last anti-CD20 dose", "notes": "Alternative: dapsone 100 mg PO daily if sulfa allergy (verify G6PD status first)" }, "triggers": { "relevant_regimens": [ "REG-BR-STANDARD" ], "clinical_condition": "Sustained immunosuppression from rituximab + chemotherapy" }, "rationale": "Anti-CD20 therapy combined with cytotoxic chemotherapy substantially prolongs B-cell depletion and increases PJP risk for months after completion of treatment.\n", "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25" }, { "id": "SUP-TLS-PROPHYLAXIS", "intervention_type": "prophylaxis", "name": "Tumor lysis syndrome prophylaxis", "name_ua": "Профілактика синдрому лізису пухлини", "standard_intervention": { "drug_id": "DRUG-ALLOPURINOL", "dose": "300 mg PO daily", "schedule": "Start 24-48h before chemotherapy; continue 5-7 days", "notes": "Plus IV hydration 2-3 L/m²/day" }, "triggers": { "relevant_regimens": [ "REG-BR-STANDARD" ], "clinical_condition": "High tumor burden: bulky disease (>=7 cm), elevated LDH, or rapid clinical progression" }, "rationale": "TLS risk is moderate-to-high in bulky indolent lymphoma starting cytoreductive therapy. Prophylaxis with allopurinol + hydration reduces hyperuricemia and downstream renal injury.\n", "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25" }, { "id": "SUP-ANTIEMETIC-PREMED", "intervention_type": "premedication", "name": "Antiemetic premedication for moderately emetogenic chemotherapy", "name_ua": "Антиеметична премедикація", "standard_intervention": { "drug_id": "DRUG-ONDANSETRON", "dose": "8 mg IV", "schedule": "30 minutes before chemotherapy; then 8 mg PO q8h × 24-48h", "notes": "Add dexamethasone 8-12 mg IV for higher emetogenicity" }, "triggers": { "relevant_regimens": [ "REG-BR-STANDARD" ] }, "rationale": "Bendamustine is moderately emetogenic; standard 5-HT3 antagonist prevents acute and delayed nausea/vomiting.\n", "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25" } ], "contraindications_data": [ { "id": "CI-HBV-NO-PROPHYLAXIS", "severity": "absolute", "trigger": { "type": "patient_condition", "conditions": [ { "patient_condition": "HBsAg+ OR anti-HBc+" }, { "patient_condition": "no concurrent HBV antiviral prophylaxis prescribed" } ], "logic": "AND" }, "description": "Active or latent HBV without antiviral prophylaxis is an absolute contraindication to starting B-cell-depleting / immunomodulatory monoclonal antibody therapy (anti-CD20, anti-CD30 ADC, anti-CD38). Severe HBV reactivation hepatitis risk including fulminant hepatic failure.", "description_ua": "Активний або латентний HBV без противірусної профілактики — абсолютне протипоказання до моноклональних антитіл, що вичерпують B-клітини або імуномодулюючих (anti-CD20, anti-CD30 ADC, anti-CD38)", "alternative_actions": [ "Start entecavir 0.5 mg PO daily (or tenofovir) — SUP-HBV-PROPHYLAXIS — before first dose", "Refer to hepatologist for shared management; HBV-DNA q-cycle monitoring", "Defer therapy until prophylaxis confirmed and first dose of antiviral administered", "Continue antiviral ≥12 months after last dose of immunosuppressive antibody" ], "affects_indications": [], "affects_drugs": [ "DRUG-RITUXIMAB", "DRUG-OBINUTUZUMAB", "DRUG-BRENTUXIMAB-VEDOTIN", "DRUG-DARATUMUMAB" ], "affects_regimens": [ "REG-BR-STANDARD" ], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-EASL-HCV-2023", "SRC-NCCN-MM-2025" ], "last_reviewed": "2026-04-27", "notes": "Triggered by RF-HBV-COINFECTION / RF-UNIVERSAL-HBV-REACTIVATION-RISK; resolved by adding SUP-HBV-PROPHYLAXIS to plan. Extended 2026-04-27 to cover anti-CD30 ADC (brentuximab vedotin) used in CHL A+AVD and anti-CD38 mAbs (daratumumab, isatuximab) used in MM regimens — both classes have documented HBV reactivation risk per their FDA labels and NCCN guidelines.\n" }, { "id": "CI-LVEF-LOW-FOR-ANTHRACYCLINE", "severity": "absolute", "trigger": { "type": "lab_result", "conditions": [ { "patient_condition": "Baseline LVEF <50% by echocardiogram or MUGA" } ], "logic": "AND" }, "description": "Pre-treatment LVEF <50% is an absolute contraindication to anthracycline-containing regimens (R-CHOP, Pola-R-CHP, ABVD, BV-AVD, etc.). Cardiotoxicity from doxorubicin is dose-cumulative and often irreversible; starting with already-impaired function risks acute decompensation.", "description_ua": "LVEF <50% на baseline — абсолютне протипоказання до anthracycline-вмісних регімів (R-CHOP, Pola-R-CHP, ABVD, BV-AVD). Кардіотоксичність доксорубіцину доза-кумулятивна і часто незворотна.", "alternative_actions": [ "Cardiology consult — confirm LVEF + assess reversible causes (treat HTN, ischemia, etc.)", "Consider non-anthracycline regimen: R-CEOP (etoposide replaces doxorubicin), R-mini-CHOP for elderly, R-bendamustine for selected patients", "Liposomal doxorubicin in selected cases (lower cardiotoxicity per dose)", "Dexrazoxane cardioprotectant if anthracycline absolutely required" ], "affects_indications": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "affects_drugs": [ "DRUG-DOXORUBICIN" ], "affects_regimens": [ "REG-R-CHOP", "REG-POLA-R-CHP" ], "sources": [ "SRC-NCCN-BCELL-2025" ], "last_reviewed": "2026-04-25", "notes": "Cumulative anthracycline lifetime threshold ~450-500 mg/m² doxorubicin. Borderline LVEF (50-55%) — proceed with serial echo monitoring. Trastuzumab + anthracycline combination separately contraindicated (additive cardiotoxicity).\n" }, { "id": "CI-BORTEZOMIB-SEVERE-NEUROPATHY", "severity": "absolute", "trigger": { "type": "patient_condition", "conditions": [ { "patient_condition": "Pre-existing Grade ≥2 peripheral neuropathy with pain OR Grade ≥3 peripheral neuropathy" } ], "logic": "AND" }, "description": "Severe pre-existing peripheral neuropathy is an absolute contraindication to bortezomib — therapy will likely worsen the neuropathy to a disabling and often permanent extent.", "description_ua": "Виражена периферична невропатія до початку терапії — абсолютне протипоказання до бортезомібу. Терапія з високою імовірністю поглибить невропатію до інвалідизуючого та часто стійкого ступеня.", "alternative_actions": [ "Consider carfilzomib-based regimen (KRd) — different proteasome inhibitor with lower neuropathy rate", "Consider isatuximab-Rd or daratumumab-Rd quadruplet (anti-CD38 + IMiD without proteasome inhibitor)", "Neurology consult for baseline workup and reversibility assessment", "Document neuropathy grade with NCCN/CTCAE before any decision" ], "affects_indications": [ "IND-MM-1L-VRD", "IND-MM-1L-DVRD" ], "affects_drugs": [ "DRUG-BORTEZOMIB" ], "affects_regimens": [ "REG-VRD", "REG-DARA-VRD" ], "sources": [ "SRC-NCCN-MM-2025" ], "last_reviewed": "2026-04-25", "notes": "Mild Grade 1 neuropathy without pain is NOT a contraindication — the SC weekly bortezomib schedule (already standard in REG-VRD and REG-DARA-VRD) has substantially reduced the neuropathy rate vs the older biweekly IV schedule. Document grade carefully — \"neuropathy\" reported by patient history without clinical exam is insufficient.\n" } ] } ], "sequencing_tracks": [], "fda_compliance": { "schema_version": null, "intended_use": "Outpatient oncology treatment planning to support tumor-board discussion. For independent clinician review; not for autonomous clinical decision-making.", "hcp_user_specification": "Licensed oncologist or hematologist participating in a multidisciplinary tumor board. Intended user must be qualified to independently review the basis of every recommendation.", "patient_population_match": "Adults with confirmed DIS-DLBCL-NOS diagnosis at line of therapy 1.", "algorithm_summary": "Select default + alternative Indication for first-line newly-diagnosed DLBCL NOS based on IPI risk. Outputs the two-plan pair (R-CHOP standard vs Pola-R-CHP intensified) per CHARTER §2.\n", "data_sources_summary": [ "SRC-ESMO-LYMPHOMA-2025: Lymphomas: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up (2025)", "SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)", "SRC-POLARIX-TILLY-2022: Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma (2022)" ], "source_links": { "SRC-ESMO-LYMPHOMA-2025": "https://www.annalsofoncology.org/article/S0923-7534(25)00911-1/fulltext", "SRC-NCCN-BCELL-2025": "https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480", "SRC-POLARIX-TILLY-2022": "https://pubmed.ncbi.nlm.nih.gov/34904799" }, "data_limitations": [], "automation_bias_warning": "Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.", "time_critical": false }, "trace": [ { "step": 1, "outcome": false, "branch": { "next_step": 2 }, "fired_red_flags": [], "winner_red_flag": null }, { "step": 2, "outcome": false, "branch": { "next_step": 3 }, "fired_red_flags": [], "winner_red_flag": null }, { "step": 3, "outcome": true, "branch": { "result": "IND-DLBCL-1L-RCHOP" }, "fired_red_flags": [ "RF-IPI-LOW", "RF-FITNESS-ECOG-FIT" ], "winner_red_flag": "RF-FITNESS-ECOG-FIT" } ], "warnings": [], "annotations": [], "access_matrix": { "schema_version": null, "rows": [ { "schema_version": null, "track_id": "standard", "track_label": "Стандартний план", "regimen_id": "REG-R-CHOP", "regimen_name": "Rituximab + CHOP (R-CHOP), 6 cycles", "drug_ids": [ "DRUG-RITUXIMAB", "DRUG-CYCLOPHOSPHAMIDE", "DRUG-DOXORUBICIN", "DRUG-VINCRISTINE", "DRUG-PREDNISONE" ], "registered_in_ua": true, "reimbursed_nszu": true, "cost_self_pay_min": null, "cost_self_pay_max": null, "cost_reimbursed_min": null, "cost_reimbursed_max": null, "cost_per_unit": null, "cost_last_updated": null, "cost_is_stale": false, "primary_pathway_id": null, "pathway_alternative_ids": [], "notes": [] }, { "schema_version": null, "track_id": "aggressive", "track_label": "Агресивний план", "regimen_id": "REG-POLA-R-CHP", "regimen_name": "Polatuzumab vedotin + Rituximab + CHP (Pola-R-CHP), 6 cycles + 2× rituximab", "drug_ids": [ "DRUG-POLATUZUMAB-VEDOTIN", "DRUG-RITUXIMAB", "DRUG-CYCLOPHOSPHAMIDE", "DRUG-DOXORUBICIN", "DRUG-PREDNISONE" ], "registered_in_ua": false, "reimbursed_nszu": false, "cost_self_pay_min": null, "cost_self_pay_max": null, "cost_reimbursed_min": null, "cost_reimbursed_max": null, "cost_per_unit": null, "cost_last_updated": null, "cost_is_stale": false, "primary_pathway_id": null, "pathway_alternative_ids": [], "notes": [ "1/5 component drug(s) not registered in Ukraine", "1/5 component drug(s) not on НСЗУ formulary" ] } ], "generated_at": "2026-10-18T12:08:55.203162+00:00", "notes": [] }, "variant_actionability": [] }, "trace": [ { "step": 1, "outcome": false, "branch": { "next_step": 2 }, "fired_red_flags": [], "winner_red_flag": null }, { "step": 2, "outcome": false, "branch": { "next_step": 3 }, "fired_red_flags": [], "winner_red_flag": null }, { "step": 3, "outcome": true, "branch": { "result": "IND-DLBCL-1L-RCHOP" }, "fired_red_flags": [ "RF-IPI-LOW", "RF-FITNESS-ECOG-FIT" ], "winner_red_flag": "RF-FITNESS-ECOG-FIT" } ], "warnings": [], "experimental_options": null }, "mdt": { "patient_id": "SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE", "plan_id": "PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1", "disease_id": "DIS-DLBCL-NOS", "required_roles": [ { "role_id": "hematologist", "role_name": "Гематолог / онкогематолог", "reason": "Лімфомний діагноз — провідна спеціальність для терапевтичного ведення.", "trigger_type": "diagnosis_complexity", "priority": "required", "linked_findings": [ "DIS-DLBCL-NOS" ], "linked_questions": [ "OQ-LDH-CURRENT" ], "skill": { "skill_id": "hematologist", "name": "Гематолог / онкогематолог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-NCCN-AML-2025", "SRC-NCCN-MM-2025", "SRC-NCCN-MPN-2025", "SRC-EHA-WORKUP-2024", "SRC-ESMO-MZL-2024", "SRC-BSH-MZL-2024" ], "domain": "hematology_oncology", "notes": "STUB — required role for any lymphoma/MM/leukemia plan; pending Clinical Co-Lead sign-off per CHARTER §6.1.", "signoffs": 0, "review_status": "stub" } } ], "recommended_roles": [ { "role_id": "clinical_pharmacist", "role_name": "Клінічний фармацевт", "reason": "Хіміоімунотерапевтичний схема — drug-drug interactions, dose adjustments, premedication.", "trigger_type": "treatment_domain", "priority": "recommended", "linked_findings": [ "aggressive-track" ], "linked_questions": [], "skill": { "skill_id": "clinical_pharmacist", "name": "Клінічний фармацевт", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [], "domain": "clinical_pharmacy", "notes": "STUB — drug-drug interactions, dose adjustments, premedication, supportive care.", "signoffs": 0, "review_status": "stub" } }, { "role_id": "infectious_disease_hepatology", "role_name": "Інфекціоніст / гепатолог", "reason": "Активна вірусна етіологія (HCV/HBV) потребує паралельного ведення антивірусної терапії та оцінки реактивації.", "trigger_type": "molecular_data", "priority": "recommended", "linked_findings": [ "HBV-serology" ], "linked_questions": [], "skill": { "skill_id": "infectious_disease_hepatology", "name": "Інфекціоніст / гепатолог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-EASL-HCV-2023", "SRC-NCCN-BCELL-2025" ], "domain": "infectious_diseases", "notes": "STUB — escalates on viral etiology (HCV/HBV/HIV) or anti-CD20 with HBV reactivation risk.", "signoffs": 0, "review_status": "stub" } }, { "role_id": "pathologist", "role_name": "Патолог (загальний)", "reason": "Підтвердження гістології лімфоми + оцінка ризику трансформації (DLBCL/Richter).", "trigger_type": "diagnosis_complexity", "priority": "recommended", "linked_findings": [ "histology" ], "linked_questions": [ "OQ-BIOMARKER-BCL2-EXPRESSION-IHC", "OQ-BIOMARKER-DLBCL-COO-HANS" ], "skill": { "skill_id": "pathologist", "name": "Патолог (загальний)", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-EHA-WORKUP-2024" ], "domain": "pathology", "notes": "STUB — generic pathologist for solid-tumor histology. Hematologic neoplasms route to hematopathologist (separate skill) in future rule revision; per CHARTER §15.2 C7 either way.", "signoffs": 0, "review_status": "stub" } } ], "optional_roles": [], "open_questions": [ { "id": "OQ-STAGING-COMPLETE", "question": "Чи виконано повне стадіювання (Lugano + PET/CT або CT)?", "owner_role": "radiologist", "blocking": false, "rationale": "Прогноз і вибір треку залежать від stage та tumor burden.", "linked_findings": [ "lugano_stage", "pet_ct_date" ] }, { "id": "OQ-LDH-CURRENT", "question": "Який актуальний LDH? Маркер пухлинного навантаження і трансформації.", "owner_role": "hematologist", "blocking": false, "rationale": "LDH входить у прогностичні індекси індолентних лімфом.", "linked_findings": [ "ldh_ratio_to_uln" ] }, { "id": "OQ-BIOMARKER-BCL2-EXPRESSION-IHC", "question": "What is the status of BCL2 expression by IHC (BIO-BCL2-EXPRESSION-IHC)? It is required by track(s): IND-DLBCL-1L-RCHOP, IND-DLBCL-1L-POLA-R-CHP. Expected value: BCL2-IHC ≥50% combined with MYC-IHC ≥40% defines double-expressor (DEL) phenotype — poorer prognosis but not an excluder; HGBL-DH (FISH double-hit) must be ruled out.", "owner_role": "pathologist", "blocking": true, "rationale": "A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.", "linked_findings": [ "BIO-BCL2-EXPRESSION-IHC" ] }, { "id": "OQ-BIOMARKER-DLBCL-COO-HANS", "question": "What is the status of Cell-of-origin classification (Hans IHC algorithm) (BIO-DLBCL-COO-HANS)? It is required by track(s): IND-DLBCL-1L-RCHOP, IND-DLBCL-1L-POLA-R-CHP. Expected value: GCB or non-GCB by Hans algorithm — non-GCB has worse R-CHOP outcomes; some centres consider R-CHOEP for non-GCB.", "owner_role": "pathologist", "blocking": true, "rationale": "A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.", "linked_findings": [ "BIO-DLBCL-COO-HANS" ] } ], "talk_tree": [ { "step": 1, "owner_role": "pathologist", "topic": "Biomarker status", "action": "What is the status of BCL2 expression by IHC (BIO-BCL2-EXPRESSION-IHC)? It is required by track(s): IND-DLBCL-1L-RCHOP, IND-DLBCL-1L-POLA-R-CHP. Expected value: BCL2-IHC ≥50% combined with MYC-IHC ≥40% defines double-expressor (DEL) phenotype — poorer prognosis but not an excluder; HGBL-DH (FISH double-hit) must be ruled out.", "blocking": true, "linked_questions": [ "OQ-BIOMARKER-BCL2-EXPRESSION-IHC" ], "linked_findings": [ "BIO-BCL2-EXPRESSION-IHC" ] }, { "step": 2, "owner_role": "pathologist", "topic": "Biomarker status", "action": "What is the status of Cell-of-origin classification (Hans IHC algorithm) (BIO-DLBCL-COO-HANS)? It is required by track(s): IND-DLBCL-1L-RCHOP, IND-DLBCL-1L-POLA-R-CHP. Expected value: GCB or non-GCB by Hans algorithm — non-GCB has worse R-CHOP outcomes; some centres consider R-CHOEP for non-GCB.", "blocking": true, "linked_questions": [ "OQ-BIOMARKER-DLBCL-COO-HANS" ], "linked_findings": [ "BIO-DLBCL-COO-HANS" ] }, { "step": 3, "owner_role": "hematologist", "topic": "Staging / disease burden", "action": "Який актуальний LDH? Маркер пухлинного навантаження і трансформації.", "blocking": false, "linked_questions": [ "OQ-LDH-CURRENT" ], "linked_findings": [ "ldh_ratio_to_uln" ] }, { "step": 4, "owner_role": "radiologist", "topic": "Staging / disease burden", "action": "Чи виконано повне стадіювання (Lugano + PET/CT або CT)?", "blocking": false, "linked_questions": [ "OQ-STAGING-COMPLETE" ], "linked_findings": [ "lugano_stage", "pet_ct_date" ] }, { "step": 5, "owner_role": "clinical_pharmacist", "topic": "Specialist review", "action": "Хіміоімунотерапевтичний схема — drug-drug interactions, dose adjustments, premedication.", "blocking": false, "linked_questions": [], "linked_findings": [ "aggressive-track" ] }, { "step": 6, "owner_role": "infectious_disease_hepatology", "topic": "Specialist review", "action": "Активна вірусна етіологія (HCV/HBV) потребує паралельного ведення антивірусної терапії та оцінки реактивації.", "blocking": false, "linked_questions": [], "linked_findings": [ "HBV-serology" ] } ], "data_quality_summary": { "status": "incomplete_for_default_track", "doctor_summary": "Default-track review is incomplete until required biomarker gaps are resolved.", "missing_critical_fields": [ "lugano_stage" ], "missing_recommended_fields": [ "ldh_ratio_to_uln", "fib4_index", "pet_ct_date" ], "missing_field_details": [ { "field": "lugano_stage", "label": "Lugano stage", "label_uk": "Стадія Lugano", "severity": "critical", "owner_role": "radiologist", "why_it_matters": "Defines lymphoma extent and supports tumor-burden and response-assessment decisions.", "why_it_matters_uk": "Визначає поширеність лімфоми та підтримує оцінку пухлинного навантаження і відповіді.", "doctor_action": "Document Lugano stage from PET/CT or contrast CT staging.", "doctor_action_uk": "Задокументувати стадію Lugano за PET/CT або контрастним CT.", "blocked_red_flags": [] }, { "field": "ldh_ratio_to_uln", "label": "LDH ratio to ULN", "label_uk": "LDH відносно ВМН", "severity": "recommended", "owner_role": "medical_oncologist", "why_it_matters": "Supports prognostic scoring and aggressive-biology flags.", "why_it_matters_uk": "Потрібно для прогностичних індексів і прапорців агресивної біології.", "doctor_action": "Enter LDH with local upper limit of normal.", "doctor_action_uk": "Внести LDH разом із локальною верхньою межею норми.", "blocked_red_flags": [] }, { "field": "fib4_index", "label": "FIB-4 liver fibrosis index", "label_uk": "Індекс фіброзу печінки FIB-4", "severity": "recommended", "owner_role": "infectious_disease_hepatology", "why_it_matters": "Screens hepatic fibrosis risk before hepatotoxic therapy or antiviral coordination.", "why_it_matters_uk": "Скринінгує ризик фіброзу печінки перед гепатотоксичною терапією або координацією противірусного лікування.", "doctor_action": "Calculate FIB-4 from age, AST, ALT, and platelet count.", "doctor_action_uk": "Розрахувати FIB-4 за віком, AST, ALT і кількістю тромбоцитів.", "blocked_red_flags": [] }, { "field": "pet_ct_date", "label": "PET/CT date", "label_uk": "Дата PET/CT", "severity": "recommended", "owner_role": "radiologist", "why_it_matters": "Shows whether baseline staging is recent enough for treatment planning and later response comparison.", "why_it_matters_uk": "Показує, чи базове стадіювання достатньо актуальне для планування лікування і подальшого порівняння відповіді.", "doctor_action": "Document baseline PET/CT date or explain alternative staging modality.", "doctor_action_uk": "Задокументувати дату базового PET/CT або пояснити альтернативний метод стадіювання.", "blocked_red_flags": [] } ], "ambiguous_findings": [], "unevaluated_red_flags": [ "RF-AAIPI-HIGH", "RF-CHRONIC-HIV-MALIGNANCY-PREVENTION", "RF-DLBCL-CART-INELIGIBLE-POST-2L", "RF-DLBCL-CD20-POS-EPCORITAMAB-CANDIDATE", "RF-DLBCL-CD20-POS-GLOFITAMAB-CANDIDATE", "RF-DLBCL-CD79B-MUT-MCD-CANDIDATE", "RF-DLBCL-CNS-RISK", "RF-DLBCL-FRAILTY-AGE", "RF-DLBCL-HIGH-IPI", "RF-DLBCL-HIGH-RISK-BIOLOGY", "RF-DLBCL-INFECTION-SCREENING", "RF-DLBCL-TRANSFORMATION-PROGRESSION", "RF-IATROGENIC-ANTI-TNF-LYMPHOMA-PREVENTION", "RF-IATROGENIC-AZATHIOPRINE-LONGTERM-PREVENTION", "RF-IATROGENIC-METHOTREXATE-LONGTERM-LYMPHOMA-PREVENTION", "RF-IATROGENIC-TRANSPLANT-IMMUNOSUPPRESSION-LONGTERM-PREVENTION", "RF-IATROGENIC-TRANSPLANT-IMMUNOSUPPRESSION-PREVENTION", "RF-IPI-HIGH", "RF-IPI-INTERMEDIATE", "RF-IPI-LOW", "RF-OCC-GLYPHOSATE-PREVENTION", "RF-OCC-PCB-PREVENTION" ], "field_unlocks": {}, "biomarker_coverage": { "required_total": 8, "required_known": 6, "required_missing": 2, "coverage_percent": 75, "known": [ { "biomarker_id": "BIO-CD20-IHC", "label": "CD20 expression by immunohistochemistry", "value_constraint": "positive (CD20+)", "owner_role": "pathologist", "tracks": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "default_track": true, "known": true, "matched_field": "BIO-CD20-IHC" }, { "biomarker_id": "BIO-CD79B-IHC", "label": "CD79b expression by IHC (target of polatuzumab vedotin)", "value_constraint": "positive (CD79b is the polatuzumab vedotin target; expressed in nearly all B-cell lymphomas including DLBCL)", "owner_role": "pathologist", "tracks": [ "IND-DLBCL-1L-POLA-R-CHP" ], "default_track": false, "known": true, "matched_field": "BIO-CD79B-IHC" }, { "biomarker_id": "BIO-DLBCL-IPI", "label": "International Prognostic Index (IPI) for DLBCL", "value_constraint": "IPI 0-5; R-CHOP preferred for IPI 0-1; for IPI ≥2 see Pola-R-CHP", "owner_role": "medical_oncologist", "tracks": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "default_track": true, "known": true, "matched_field": "ipi_score" }, { "biomarker_id": "BIO-HBV-STATUS", "label": "HBV status (HBsAg + anti-HBc serology)", "value_constraint": "any value valid (categorical etiology gate; HBsAg+ or anti-HBc+ → entecavir prophylaxis mandatory before first rituximab dose; engine consumes the input to fire RF-UNIVERSAL-HBV-REACTIVATION-RISK)", "owner_role": "medical_oncologist", "tracks": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "default_track": true, "known": true, "matched_field": "BIO-HBV-STATUS" }, { "biomarker_id": "BIO-HCV-STATUS", "label": "HCV status (anti-HCV antibody screening)", "value_constraint": "any value valid (categorical etiology gate; anti-HCV+ → reflex BIO-HCV-RNA; coordinate DAA with hepatology; does not change R-CHOP regimen choice)", "owner_role": "medical_oncologist", "tracks": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "default_track": true, "known": true, "matched_field": "BIO-HCV-STATUS" }, { "biomarker_id": "BIO-HIV-STATUS", "label": "HIV status (4th-gen Ag/Ab combo screening)", "value_constraint": "any value valid (categorical etiology gate; HIV+ → cART throughout, PJP/MAC prophylaxis if CD4 < 200, CNS prophylaxis regardless of CNS-IPI; integrase-inhibitor backbone preferred to avoid ritonavir-vincristine interaction)", "owner_role": "medical_oncologist", "tracks": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "default_track": true, "known": true, "matched_field": "BIO-HIV-STATUS" } ], "missing": [ { "biomarker_id": "BIO-BCL2-EXPRESSION-IHC", "label": "BCL2 expression by IHC", "value_constraint": "BCL2-IHC ≥50% combined with MYC-IHC ≥40% defines double-expressor (DEL) phenotype — poorer prognosis but not an excluder; HGBL-DH (FISH double-hit) must be ruled out", "owner_role": "pathologist", "tracks": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "default_track": true, "known": false, "matched_field": null }, { "biomarker_id": "BIO-DLBCL-COO-HANS", "label": "Cell-of-origin classification (Hans IHC algorithm)", "value_constraint": "GCB or non-GCB by Hans algorithm — non-GCB has worse R-CHOP outcomes; some centres consider R-CHOEP for non-GCB", "owner_role": "pathologist", "tracks": [ "IND-DLBCL-1L-RCHOP", "IND-DLBCL-1L-POLA-R-CHP" ], "default_track": true, "known": false, "matched_field": null } ] }, "missing_default_biomarkers": 2, "fields_present_count": 19, "fields_expected_count": 8 }, "aggregation_summary": { "kb_entities_loaded": 4273, "kb_sources_cited": [ "SRC-ESMO-LYMPHOMA-2025", "SRC-NCCN-BCELL-2025", "SRC-POLARIX-TILLY-2022" ], "indications_evaluated": 2, "biomarkers_referenced": [ "BIO-BCL2-EXPRESSION-IHC", "BIO-CD20-IHC", "BIO-CD79B-IHC", "BIO-DLBCL-COO-HANS", "BIO-DLBCL-IPI", "BIO-HBV-STATUS", "BIO-HCV-STATUS", "BIO-HIV-STATUS" ], "red_flags_total_in_kb": 715, "red_flags_fired": [ "RF-IPI-LOW", "RF-FITNESS-ECOG-FIT" ], "open_questions_raised": 4, "live_api_clients_available": [ "SRC-CTGOV-REGISTRY", "SRC-PUBMED", "SRC-DAILYMED", "SRC-OPENFDA" ], "live_api_clients_invoked": [] }, "warnings": [], "provenance": { "nodes": [ { "id": "DIS-DLBCL-NOS", "type": "diagnosis", "label": "DIS-DLBCL-NOS" }, { "id": "IND-DLBCL-1L-RCHOP", "type": "plan_section", "label": "Стандартний план" }, { "id": "IND-DLBCL-1L-POLA-R-CHP", "type": "plan_section", "label": "Агресивний план" } ], "edges": [ { "from": "DIS-DLBCL-NOS", "to": "IND-DLBCL-1L-RCHOP", "kind": "candidate" }, { "from": "DIS-DLBCL-NOS", "to": "IND-DLBCL-1L-POLA-R-CHP", "kind": "candidate" } ], "events": [ { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-001", "timestamp": "2026-10-18T12:08:55.205127+00:00", "actor_role": "engine", "actor_id": null, "event_type": "confirmed", "target_type": "plan_section", "target_id": "PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1", "summary": "Engine згенерував план PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1 (версія 1).", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-002", "timestamp": "2026-10-18T12:08:55.205135+00:00", "actor_role": "engine", "actor_id": null, "event_type": "requested_data", "target_type": "plan_section", "target_id": "hematologist", "summary": "Запрошено роль 'Гематолог / онкогематолог' (priority=required): Лімфомний діагноз — провідна спеціальність для терапевтичного ведення.", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-003", "timestamp": "2026-10-18T12:08:55.205140+00:00", "actor_role": "engine", "actor_id": null, "event_type": "requested_data", "target_type": "plan_section", "target_id": "clinical_pharmacist", "summary": "Запрошено роль 'Клінічний фармацевт' (priority=recommended): Хіміоімунотерапевтичний схема — drug-drug interactions, dose adjustments, premedication.", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-004", "timestamp": "2026-10-18T12:08:55.205144+00:00", "actor_role": "engine", "actor_id": null, "event_type": "requested_data", "target_type": "plan_section", "target_id": "infectious_disease_hepatology", "summary": "Запрошено роль 'Інфекціоніст / гепатолог' (priority=recommended): Активна вірусна етіологія (HCV/HBV) потребує паралельного ведення антивірусної терапії та оцінки реактивації.", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-005", "timestamp": "2026-10-18T12:08:55.205147+00:00", "actor_role": "engine", "actor_id": null, "event_type": "requested_data", "target_type": "plan_section", "target_id": "pathologist", "summary": "Запрошено роль 'Патолог (загальний)' (priority=recommended): Підтвердження гістології лімфоми + оцінка ризику трансформації (DLBCL/Richter).", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-006", "timestamp": "2026-10-18T12:08:55.205151+00:00", "actor_role": "engine", "actor_id": null, "event_type": "added_question", "target_type": "plan_section", "target_id": "OQ-STAGING-COMPLETE", "summary": "Підняте питання для radiologist (blocking=False): Чи виконано повне стадіювання (Lugano + PET/CT або CT)?", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-007", "timestamp": "2026-10-18T12:08:55.205154+00:00", "actor_role": "engine", "actor_id": null, "event_type": "added_question", "target_type": "plan_section", "target_id": "OQ-LDH-CURRENT", "summary": "Підняте питання для hematologist (blocking=False): Який актуальний LDH? Маркер пухлинного навантаження і трансформації.", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-008", "timestamp": "2026-10-18T12:08:55.205157+00:00", "actor_role": "engine", "actor_id": null, "event_type": "added_question", "target_type": "plan_section", "target_id": "OQ-BIOMARKER-BCL2-EXPRESSION-IHC", "summary": "Підняте питання для pathologist (blocking=True): What is the status of BCL2 expression by IHC (BIO-BCL2-EXPRESSION-IHC)? It is required by track(s): IND-DLBCL-1L-RCHOP, IND-DLBCL-1L-POLA-R-CHP. Expected value: BCL2-IHC ≥50% combined with MYC-IHC ≥40% defines double-expressor (DEL) phenotype — poorer prognosis but not an excluder; HGBL-DH (FISH double-hit) must be ruled out.", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-009", "timestamp": "2026-10-18T12:08:55.205160+00:00", "actor_role": "engine", "actor_id": null, "event_type": "added_question", "target_type": "plan_section", "target_id": "OQ-BIOMARKER-DLBCL-COO-HANS", "summary": "Підняте питання для pathologist (blocking=True): What is the status of Cell-of-origin classification (Hans IHC algorithm) (BIO-DLBCL-COO-HANS)? It is required by track(s): IND-DLBCL-1L-RCHOP, IND-DLBCL-1L-POLA-R-CHP. Expected value: GCB or non-GCB by Hans algorithm — non-GCB has worse R-CHOP outcomes; some centres consider R-CHOEP for non-GCB.", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-010", "timestamp": "2026-10-18T12:08:55.205165+00:00", "actor_role": "engine", "actor_id": null, "event_type": "flagged_risk", "target_type": "red_flag", "target_id": "RF-IPI-LOW", "summary": "RedFlag RF-IPI-LOW спрацював на step 3 алгоритму ALGO-DLBCL-1L.", "evidence_refs": [] }, { "event_id": "EV-PLAN-SYNTHETIC-REVIEW-ANTI_HBC_TOTAL-POSITIVE-V1-011", "timestamp": "2026-10-18T12:08:55.205168+00:00", "actor_role": "engine", "actor_id": null, "event_type": "flagged_risk", "target_type": "red_flag", "target_id": "RF-FITNESS-ECOG-FIT", "summary": "RedFlag RF-FITNESS-ECOG-FIT спрацював на step 3 алгоритму ALGO-DLBCL-1L.", "evidence_refs": [] } ], "plan_version": 1 }, "activated_skills": [ { "skill_id": "hematologist", "name": "Гематолог / онкогематолог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-NCCN-AML-2025", "SRC-NCCN-MM-2025", "SRC-NCCN-MPN-2025", "SRC-EHA-WORKUP-2024", "SRC-ESMO-MZL-2024", "SRC-BSH-MZL-2024" ], "domain": "hematology_oncology", "notes": "STUB — required role for any lymphoma/MM/leukemia plan; pending Clinical Co-Lead sign-off per CHARTER §6.1.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "clinical_pharmacist", "name": "Клінічний фармацевт", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [], "domain": "clinical_pharmacy", "notes": "STUB — drug-drug interactions, dose adjustments, premedication, supportive care.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "infectious_disease_hepatology", "name": "Інфекціоніст / гепатолог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-EASL-HCV-2023", "SRC-NCCN-BCELL-2025" ], "domain": "infectious_diseases", "notes": "STUB — escalates on viral etiology (HCV/HBV/HIV) or anti-CD20 with HBV reactivation risk.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "pathologist", "name": "Патолог (загальний)", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-EHA-WORKUP-2024" ], "domain": "pathology", "notes": "STUB — generic pathologist for solid-tumor histology. Hematologic neoplasms route to hematopathologist (separate skill) in future rule revision; per CHARTER §15.2 C7 either way.", "signoffs": 0, "review_status": "stub" } ], "skill_catalog": [ { "skill_id": "cellular_therapy_specialist", "name": "Спеціаліст з клітинної терапії (CAR-T)", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025" ], "domain": "cellular_therapy", "notes": "STUB — CAR-T product selection (axi-cel, tisa-cel, liso-cel, brexu-cel) + bridging therapy + CRS/ICANS management. Modern standard for refractory/relapsed DLBCL/MCL/CLL after 2nd line. Triggers: line_of_therapy ≥ 2 + aggressive_b_cell_lymphoma + fit_for_cellular_therapy. Funding pathway flag mandatory (not НСЗУ-reimbursed in UA — clinical trial / charitable).", "signoffs": 0, "review_status": "stub" }, { "skill_id": "clinical_pharmacist", "name": "Клінічний фармацевт", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [], "domain": "clinical_pharmacy", "notes": "STUB — drug-drug interactions, dose adjustments, premedication, supportive care.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "hematologist", "name": "Гематолог / онкогематолог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-NCCN-AML-2025", "SRC-NCCN-MM-2025", "SRC-NCCN-MPN-2025", "SRC-EHA-WORKUP-2024", "SRC-ESMO-MZL-2024", "SRC-BSH-MZL-2024" ], "domain": "hematology_oncology", "notes": "STUB — required role for any lymphoma/MM/leukemia plan; pending Clinical Co-Lead sign-off per CHARTER §6.1.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "hematopathologist", "name": "Гематопатолог (специфічно для лімфом / лейкозів / мієломи)", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-NCCN-AML-2025", "SRC-NCCN-MM-2025", "SRC-EHA-WORKUP-2024" ], "domain": "hematopathology", "notes": "STUB — subspecialized pathologist for lymphoid + myeloid neoplasms. Owns: WHO 5th-ed classification mapping, IHC panel design (CD20/CD3/CD5/CD10/CD23/BCL2/BCL6/MYC/Ki67), flow cytometry interpretation, FISH (MYC/BCL2/BCL6 break-apart), Hans algorithm (ABC vs GCB DLBCL), gene-rearrangement studies. Critical for differentiating lymphoma subtypes — without rich hematopathology, you can't pick the right Tier 1 algorithm.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "infectious_disease_hepatology", "name": "Інфекціоніст / гепатолог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-EASL-HCV-2023", "SRC-NCCN-BCELL-2025" ], "domain": "infectious_diseases", "notes": "STUB — escalates on viral etiology (HCV/HBV/HIV) or anti-CD20 with HBV reactivation risk.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "medical_oncologist", "name": "Медичний онколог (хіміотерапевт солідних пухлин)", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [], "domain": "solid_oncology", "notes": "STUB — placeholder for solid-tumor cases; rules minimal until first solid-tumor disease lands in KB.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "molecular_geneticist", "name": "Молекулярний генетик / молекулярний онколог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-MM-2025" ], "domain": "molecular_oncology", "notes": "STUB — escalates on actionable genomic biomarkers per R9 (_ACTIONABLE_GENOMIC_TYPES set).", "signoffs": 0, "review_status": "stub" }, { "skill_id": "palliative_care", "name": "Паліативна допомога", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [], "domain": "palliative_care", "notes": "STUB — advanced-disease symptom management and goals-of-care.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "pathologist", "name": "Патолог (загальний)", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-EHA-WORKUP-2024" ], "domain": "pathology", "notes": "STUB — generic pathologist for solid-tumor histology. Hematologic neoplasms route to hematopathologist (separate skill) in future rule revision; per CHARTER §15.2 C7 either way.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "primary_care", "name": "Сімейний лікар / терапевт", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [], "domain": "primary_care", "notes": "STUB — comorbidity management, vaccinations, post-treatment long-term follow-up.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "psychologist", "name": "Психолог / онкопсихолог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [], "domain": "psychosocial", "notes": "STUB — supportive role for distress, anxiety, treatment decision support.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "radiation_oncologist", "name": "Радіотерапевт (променева терапія)", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-ESMO-MZL-2024" ], "domain": "radiation_oncology", "notes": "STUB — extranodal MALT lymphomas often eligible for localized radiotherapy.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "radiologist", "name": "Лікар-радіолог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025" ], "domain": "diagnostic_imaging", "notes": "STUB — staging/restaging via CECT/PET-CT/MRI; reads bulky-disease and mass-mapping findings.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "social_worker_case_manager", "name": "Соціальний працівник / кейс-менеджер", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [], "domain": "psychosocial", "notes": "STUB — coordinates НСЗУ reimbursement pathway, drug access, transportation, financial counseling.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "surgical_oncologist", "name": "Хірург-онколог", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [], "domain": "surgical_oncology", "notes": "STUB — placeholder; rules minimal until first solid-tumor disease lands in KB. Episodic role for hematologic: splenectomy in splenic MZL with hypersplenism, GI surgery for selected GI lymphomas.", "signoffs": 0, "review_status": "stub" }, { "skill_id": "transplant_specialist", "name": "Спеціаліст з трансплантації (BMT)", "version": "0.1.0", "last_reviewed": "2026-04-25", "clinical_lead": null, "verified_by": [], "sources": [ "SRC-NCCN-BCELL-2025", "SRC-NCCN-MM-2025", "SRC-EHA-WORKUP-2024" ], "domain": "cellular_therapy", "notes": "STUB — autoSCT/alloSCT decision-making. Activates for: first-line consolidation in transplant-eligible MCL + high-risk DLBCL; salvage transplant for relapsed/refractory aggressive lymphomas; alloSCT for relapsed CLL/T-cell. Triggers: fit_for_transplant + ECOG ≤ 2 + age ≤ 70-75 (relative).", "signoffs": 0, "review_status": "stub" } ] } }