Patient
B-ALL-BLINA-001 · Algorithm: ALGO-B-ALL-2L
Clinical significance of mutations (ESCAT / OncoKB)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | OncoKB | Clinical significance | Drugs | Sources |
|---|
| No clinically actionable variants matched in this profile. |
Treatment options (3 tracks)
- Indication
- IND-B-ALL-BLINATUMOMAB-MRD-OR-RR
- Regimen
- Blinatumomab BiTE for MRD+ post-induction OR R/R B-ALL
- Drugs + NSZU
- Blinatumomab (DRUG-BLINATUMOMAB) R/R B-ALL: cycle 1: 9 µg/day continuous IV d1-7, then 28 µg/day d8-28 of 42-day cycle. Cycles 2-5: 28 µg/day d1-28. Up to 9 cycles. MRD+ B-ALL: 28 µg/day continuous IV d1-28 of 42-day cycle, up to 4 cycles. · Continuous IV via ambulatory infusion pump; hospitalization recommended cycle 1 d1-9 + cycle 2 d1-2; outpatient pump-driven thereafter · IV ✓ NSZU covered
- Dexamethasone (DRUG-DEXAMETHASONE) 20 mg IV before first dose of cycle 1 (CRS prophylaxis); 20 mg IV before dose escalation cycle 1 d8 · Pre-dose only; not continuous · IV ⚠ NSZU — not for this indication
- Supportive care
- SUP-TLS-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS
- Reason
- Engine default per algorithm ALGO-B-ALL-2L: {'step': 3, 'outcome': False, 'branch': {'result': 'IND-B-ALL-BLINATUMOMAB-MRD-OR-RR'}, 'fired_red_flags': [], 'winner_red_flag': None}
- Indication
- IND-B-ALL-2L-INOTUZUMAB
- Regimen
- Inotuzumab ozogamicin for R/R Ph- B-ALL 2L+ (bridge to alloHCT)
- Drugs + NSZU
- Inotuzumab ozogamicin (DRUG-INOTUZUMAB-OZOGAMICIN) Cycle 1 induction: 0.8 mg/m² IV day 1, 0.5 mg/m² IV days 8 + 15 (total 1.8 mg/m²); Cycle 2-6 consolidation post-CR: 0.5 mg/m² IV days 1, 8, 15 (total 1.5 mg/m²) · Cycles every 21-28 days; max 6 cycles; bridge to alloHCT after 1-2 cycles for transplant-eligible (limit pre-HCT exposure to mitigate VOD risk) · IV ✗ Not registered in UA
- Supportive care
- SUP-TLS-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS
- Reason
- Alternative track presented for HCP consideration
- Indication
- IND-B-ALL-3L-TISAGENLECLEUCEL
- Regimen
- Tisagenlecleucel CD19 CAR-T for R/R B-ALL ≤25 years
- Drugs + NSZU
- Fludarabine (DRUG-FLUDARABINE) 30 mg/m² IV daily × 4 days (lymphodepleting conditioning) · Days -4 to -1 before CAR-T infusion · IV ⚠ NSZU — not for this indication
- Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 500 mg/m² IV daily × 2 days (lymphodepleting conditioning) · Days -4 to -3 before CAR-T infusion · IV ⚠ NSZU — not for this indication
- Tisagenlecleucel (DRUG-TISAGENLECLEUCEL) Single IV infusion: 0.2 to 5.0 × 10⁶ CAR-positive viable T cells per kg for patients ≤50 kg; 0.1 to 2.5 × 10⁸ CAR-positive viable T cells (not weight-based) for patients >50 kg · Single infusion day 0 after lymphodepletion completion; no maintenance · IV ✗ Not registered in UA
- Supportive care
- SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB
- Reason
- Alternative track presented for HCP consideration
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Needed for |
|---|
| TEST-BCR-ABL-JAK2 | Цільові молекулярні: BCR-ABL1, JAK2 V617F, CALR, MPL | Critical | genomic | all tracks |
| TEST-BM-ASPIRATE | Аспірат кісткового мозку (цитологія + flow + цитогенетика + молекулярка) | Critical | histology | all tracks |
| TEST-BM-TREPHINE | Трепанобіопсія кісткового мозку (core-біопсія) | Critical | histology | all tracks |
| TEST-CBC | Загальний аналіз крові з лейкоцитарною формулою | Critical | lab | all tracks |
| TEST-CMP | Розширений біохімічний аналіз крові | Critical | lab | all tracks |
| TEST-COAG-PANEL | Коагулограма (ПТ/МНВ, АЧТЧ, фібриноген) | Critical | lab | all tracks |
| TEST-FISH-PANEL | FISH-панель (специфічна для нозології) | Critical | genomic | all tracks |
| TEST-FLOW-CYTOMETRY | Імунофенотипування методом проточної цитометрії | Critical | histology | all tracks |
| TEST-HBV-SEROLOGY | Серологія HBV: HBsAg, anti-HBc, anti-HBs | Critical | lab | all tracks |
| TEST-HCV-ANTIBODY | Антитіла до HCV | Critical | lab | all tracks |
| TEST-HIV-SEROLOGY | Серологія ВІЛ (антитіла HIV-1/2 + p24) | Critical | lab | all tracks |
| TEST-KARYOTYPE | Класична цитогенетика (каріотип) | Critical | genomic | all tracks |
| TEST-LDH | Лактатдегідрогеназа (ЛДГ) | Critical | lab | all tracks |
| TEST-LFT | Печінкові проби (АЛТ, АСТ, білірубін, ЛФ, ГГТП, альбумін) | Critical | lab | all tracks |
| TEST-PREGNANCY | β-ХГЛ (тест на вагітність) | Critical | lab | all tracks |
| TEST-CMV-SEROLOGY | Серологія CMV (IgG + IgM) | Standard | lab | all tracks |
| TEST-CSF-CYTOLOGY-FLOW | Цитологія + проточна цитофлуометрія ліквору | Standard | pathology | all tracks |
| TEST-ECHO | Ехокардіографія (ТТЕ) з оцінкою ФВ ЛШ | Standard | imaging | all tracks |
| TEST-IMMUNOGLOBULINS | Кількісні імуноглобуліни (IgG, IgA, IgM) | Standard | lab | all tracks |
| TEST-MRI-BRAIN-CONTRAST | МРТ головного мозку з гадолінієвим контрастом | Standard | imaging | all tracks |
| TEST-URIC-ACID | Сечова кислота сироватки | Standard | lab | all tracks |
| TEST-NGS-LYMPHOID-PANEL | NGS-панель лімфоїдних мутацій | Desired | genomic | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Age ≥65 OR ECOG ≥3 with comorbidities — pediatric-inspired regimens (CALGB 10403, hyper-CVAD) inadequately tolerated; reduced-intensity protocol (mini-HCVD ± inotuzumab/blinatumomab) preferred.RF-B-ALL-FRAILTY-AGE
- Philadelphia-positive B-ALL (BCR-ABL1+) — TKI (imatinib/dasatinib/ponatinib) + chemotherapy is standard; Ph-like B-ALL signature requires JAK/ABL pathway-targeted addition.RF-B-ALL-HIGH-RISK-BIOLOGY
- Cardiac dysfunction (LVEF <50%) — anthracycline-based induction (hyper-CVAD A, BFM-style protocols) requires modification or substitution.RF-B-ALL-ORGAN-DYSFUNCTION
- MRD-positive at end-of-induction (≥0.01% by flow or PCR) — switch to MRD-eradication strategy (blinatumomab, inotuzumab, or alloSCT consolidation).RF-B-ALL-TRANSFORMATION-PROGRESSION
CONTRA-AGGRESSIVE
Hard contraindications to escalation
- 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.CI-HBV-NO-PROPHYLAXIS
- 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.CI-HBV-NO-PROPHYLAXIS
- Alemtuzumab causes profound, prolonged CD4+ T-cell depletion (median recovery 9-12 months). Active uncontrolled infection at baseline becomes life-threatening once cellular immunity collapses. HIV-positive status is itself an absolute contraindication — alemtuzumab on top of HIV immunosuppression has unacceptable infectious mortality.
CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-B-ALL-BLINATUMOMAB-MRD-OR-RR)
- НЕ розпочинати без CD19 confirmation — CD19-negative blasts уникають targeting; ~30% relapse-loss CD19.
- НЕ розпочинати без cytoreduction при BM blasts >50% OR PB blasts >15K — TLS + CRS ризик amplified.
- НЕ ігнорувати CRS / neurotox surveillance — hospitalization обов'язкова cycle 1 d1-9, cycle 2 d1-2.
- НЕ використовувати без on-site tocilizumab (≥2 dose) — fatal CRS можлива.
- НЕ продовжувати при Grade ≥3 neurotoxicity recurrent OR seizures — permanent discontinuation.
- НЕ призначати prophylactic systemic corticosteroids поза dexamethasone premedication — пригнічує T-cell engagement + знижує efficacy.
- НЕ забувати alloHCT-pathway для transplant-eligible — single-agent blinatumomab not curative для R/R.
Aggressive plan (IND-B-ALL-2L-INOTUZUMAB)
- НЕ призначати при confirmed history of severe VOD/SOS — absolute CI.
- НЕ перевищувати 2 цикли pre-HCT — VOD risk кумулятивний (boxed warning).
- НЕ використовувати dual-alkylator (Bu/Cy) conditioning post-inotuzumab — Bu/Flu кращий.
- НЕ ігнорувати baseline + щоциклова LFT (білірубін, ALT, AST) — hepatotoxicity prelude до VOD.
- НЕ розпочинати без CD22 confirmation — CD22-negative blasts уникають targeting.
- НЕ забувати TLS prophylaxis (allopurinol + hydration) — особливо cycle 1.
- НЕ забувати alloHCT-pathway — single-agent inotuzumab НЕ є curative.
Aggressive plan (IND-B-ALL-3L-TISAGENLECLEUCEL)
- НЕ призначати prophylactic systemic corticosteroids — пригнічує CAR-T expansion + знижує efficacy.
- НЕ розпочинати без on-site tocilizumab (мінімум 2 дози) ДО інфузії — fatal CRS можливе.
- НЕ робити в центрі без CAR-T accreditation (FACT/JACIE/REMS) — toxicity management потребує спеціалізованої команди + ICU доступу.
- НЕ пропускати baseline brain MRI — CNS-2/3 з симптомами exclusion ELIANA; ризик fatal ICANS вищий.
- НЕ ігнорувати тимчасову bridging chemotherapy (3-4 тижні manufacturing window) — disease progression в цьому вікні зменшує efficacy + може unfit пацієнта для CAR-T.
- НЕ призначати при active uncontrolled infection — лімфодеплеція + CRS = high mortality.
- НЕ забути IVIG для довготривалої hypogammaglobulinemia (IgG <400 + recurrent infections) — B-cell aplasia може тривати >12 місяців.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · Blinatumomab BiTE for MRD+ pos
42-day cycles × MRD+: up to 4 cycles; R/R: up to 9 cycles; bridge to alloHCT for transplant-eligible after MRD-negativity / CR
Aggressive plan
Induction · Inotuzumab ozogamicin for R/R
21-day cycles × Up to 6 cycles; transplant-eligible patients should bridge to alloHCT after 1-2 cycles to minimize VOD/SOS risk (boxed warning)
MDT brief
Skills (recommended) — for consideration (1)
- Клінічний фармацевт recommended
Хіміоімунотерапевтичний схема — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
Open questions (1, 0 blocking)
Data quality
- Unevaluated RedFlags: RF-B-ALL-CNS-LEUKEMIA, RF-B-ALL-EMERGENCY-TLS-LEUKOSTASIS, RF-B-ALL-FRAILTY-AGE, RF-B-ALL-HIGH-RISK-BIOLOGY, RF-B-ALL-INFECTION-SCREENING, RF-B-ALL-TRANSFORMATION-PROGRESSION
Skill catalog (1/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|
| Specialist з клітинної терапії (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Клінічний фармацевт | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Гематолог / онкогематолог | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Гематопатолог (специфічно для лімфом / лейкозів / мієломи) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Інфекціоніст / гепатолог | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Медичний онколог (хіміотерапевт солідних пухлин) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Молекулярний генетик / молекулярний онколог | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Паліативна допомога | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Патолог (загальний) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Сімейний лікар / терапевт | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Психолог / онкопсихолог | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Радіотерапевт (променева терапія) | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Лікар-радіолог | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Соціальний працівник / кейс-менеджер | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Хірург-онколог | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Specialist з трансплантації (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-BLAST-GOKBUGET-2018: Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia (2018)
- SRC-ELIANA-MAUDE-2018: Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia (2018)
- SRC-INOVATE-KANTARJIAN-2016: Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia (2016)
- SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)
Експериментальні опції (клінічні дослідження)
Третій трек плану — open-enrollment trials з ClinicalTrials.gov. Останнє оновлення: 2026-04-26. Render-time metadata; engine selection не змінюється цим блоком (CHARTER §8.3).
| NCT | Name | Phase | Статус | Спонсор | UA | Включення (фрагмент) |
|---|
| NCT07106749 | CD180 CART for Relapsed or Refractory CD180 Positive Hematologic Malignancies | PHASE1 | RECRUITING | — | |
| NCT06708897 | A Phase 1 Study of ZE50-0134 in Relapsed and Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Select Low-grad Lymphomas | PHASE1 | RECRUITING | — | |
| NCT05371808 | Economic Analysis of Early vs Delayed Therapy in Newly Diagnosed Asymptomatic High-Risk Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: | N/A | RECRUITING | — | |
| NCT07134088 | A Study of Subcutaneous Blinatumomab in Children With R/R and and MRD+ B-Cell Precursor Acute Lymphoblastic Leukemia | PHASE1 / PHASE2 | RECRUITING | — | |
| NCT03676504 | Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR | PHASE1 / PHASE2 | RECRUITING | — | |
| NCT04094311 | Study of Out of Specification for Tisagenlecleucel | PHASE3 | RECRUITING | — | |
| NCT07145411 | HPC Offered for PRESERVE Expansion | N/A | RECRUITING | — | |
| NCT05602363 | AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma | PHASE1 | RECRUITING | — | |
| NCT05618028 | Study to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets | PHASE1 | RECRUITING | — | |
| NCT04532281 | A Study of Murine CD19 CAR-T Therapy for Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancies | EARLY_PHASE1 | RECRUITING | — | |
Перевіряти статус набору безпосередньо у дослідницькому центрі. Дані ctgov можуть відставати від поточного статусу UA-сайтів.
Доступність опцій в Україні
Per-track UA registration · НСЗУ · cost · access pathway. Render-time metadata; engine selection не залежить від цих полів (CHARTER §8.3).
| Опція | Реєстрація UA | НСЗУ | Cost orientation | Access pathway |
|---|
| Aggressive plan Blinatumomab BiTE for MRD+ post-induction OR R/R B-ALL (REG-BLINATUMOMAB-B-ALL) | ✓ зареєстровано | ✓ покривається | ₴-? — verify pathway | НСЗУ formulary |
| Aggressive plan Inotuzumab ozogamicin for R/R Ph- B-ALL 2L+ (bridge to alloHCT) (REG-INOTUZUMAB-B-ALL) 1/1 component drug(s) not registered in Ukraine +1 | ✗ не зареєстровано | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Tisagenlecleucel CD19 CAR-T for R/R B-ALL ≤25 years (REG-TISAGENLECLEUCEL-B-ALL) 1/3 component drug(s) not registered in Ukraine +1 | ✗ не зареєстровано | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Trial · NCT07106749 CD180 CART for Relapsed or Refractory CD180 Positive Hematologic Malignancies No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06708897 A Phase 1 Study of ZE50-0134 in Relapsed and Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Select Low-grad Lymphomas No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05371808 Economic Analysis of Early vs Delayed Therapy in Newly Diagnosed Asymptomatic High-Risk Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07134088 A Study of Subcutaneous Blinatumomab in Children With R/R and and MRD+ B-Cell Precursor Acute Lymphoblastic Leukemia No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT03676504 Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04094311 Study of Out of Specification for Tisagenlecleucel No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07145411 HPC Offered for PRESERVE Expansion No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05602363 AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05618028 Study to Evaluate Adverse Events and Change in Disease Activity in Adult Participants With B-Cell Malignancies Receiving Oral ABBV-525 Tablets No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04532281 A Study of Murine CD19 CAR-T Therapy for Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancies No UA site listed — international referral required | — невідомо | — невідомо | self-pay: ₴0/course | Trial sponsor |
Інформація про ціни — orientation. Перевіряти у конкретній аптеці / foundation / трайл-сайті. Status updated: 2026-04-27.