Patient
VAR-PCNSL-ORGAN · Algorithm: ALGO-PCNSL-1L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| No clinically actionable variants matched in this profile. |
| Biomarker | Status |
|---|
| BIO-CD20-IHC | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
Primary current-line option
- Indication
- IND-PCNSL-1L-R-MPV
- Regimen
- R-MPV (Rituximab + HD-Methotrexate + Procarbazine + Vincristine), 5 cycles q14d
- Drugs + NSZU
- Rituximab (DRUG-RITUXIMAB) 500 mg/m² · IV day 1 · IV ✓ NSZU covered
- Methotrexate (DRUG-METHOTREXATE) 3.5 g/m² · IV 2h infusion day 2; leucovorin rescue · IV ✓ NSZU covered
- Vincristine (DRUG-VINCRISTINE) 1.4 mg/m² (max 2 mg) · IV day 2 · IV ⚠ NSZU — not for this indication
- Procarbazine (DRUG-PROCARBAZINE) 100 mg/m² · PO days 1-7 odd cycles only · PO ✗ Not registered in UA
- Supportive care
- SUP-HBV-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS, CI-RENAL-FAILURE-FOR-HD-MTX
- Reason
- Primary current-line option selected by ALGO-PCNSL-1L at step 1; branch-driving red flag: RF-PCNSL-ORGAN-DYSFUNCTION.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-PCNSL-1L-MATRIX
- Regimen
- MATRix (HD-Methotrexate + HD-Cytarabine + Thiotepa + Rituximab), 4 cycles
- Drugs + NSZU
Induction — MATRix induction × 4 cycles — HD-MTX + HD-Cytarabine + thiotepa + rituximab for PCNSL; followed by separate autoSCT consolidation regimen (BCNU + thiotepa)
- Methotrexate (DRUG-METHOTREXATE) 3.5 g/m² · IV 24h infusion day 1; leucovorin rescue from h+24 · IV ✓ NSZU covered
- Cytarabine (DRUG-CYTARABINE) 2 g/m² BID · IV days 2-3 (4 doses total) · IV ⚠ NSZU — not for this indication
- Thiotepa (DRUG-THIOTEPA) 30 mg/m² · IV day 4 · IV ✓ NSZU covered
- Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV days -5, 0 · IV ✓ NSZU covered
- Supportive care
- SUP-HBV-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-GCSF-NEUTROPENIA
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS, CI-RENAL-FAILURE-FOR-HD-MTX
- Reason
- Current-line alternative presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 1 → branch IND-PCNSL-1L-R-MPV
- RF-PCNSL-ORGAN-DYSFUNCTION ★ winner: Renal dysfunction (CrCl <50 mL/min) — high-dose methotrexate (HD-MTX, ≥3 g/m²) backbone of all PCNSL 1L regimens contraindicated; transition to non-MTX regimen or refer to specialized center. SRC-NCCN-BCELL-2025SRC-ESMO-DLBCL-2024
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CD20-IHC | CD20 Immunohistochemistry | Critical | histology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-HBV-SEROLOGY | Hepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs) | Critical | lab | — | all tracks |
| TEST-HCV-ANTIBODY | HCV Antibody | Critical | lab | — | all tracks |
| TEST-HIV-SEROLOGY | HIV Antibody/Antigen | Critical | lab | — | all tracks |
| TEST-LDH | Lactate Dehydrogenase | Critical | lab | — | all tracks |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-PREGNANCY | Beta-HCG | Critical | lab | — | standard |
| TEST-CSF-CYTOLOGY-FLOW | CSF cytology + flow cytometry | Standard | pathology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-ECHO | Echocardiography | Standard | imaging | — | all tracks |
| TEST-MRI-BRAIN-CONTRAST | MRI brain with contrast | Standard | imaging | — | all tracks |
| TEST-SLIT-LAMP-EYE-EXAM | Slit-lamp + dilated fundoscopic exam | Standard | imaging | — | all tracks |
| TEST-NGS-LYMPHOID-PANEL | Lymphoid NGS Panel | Desired | genomic | CSD Lab ✓ (code TBC) | desired (standard) |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Age >70 OR ECOG ≥3 OR CrCl 50-70 mL/min — full-dose HD-MTX (≥3.5 g/m²) carries excessive toxicity; reduced-dose MTX (1-3 g/m²) ± rituximab considered.RF-PCNSL-FRAILTY-AGE
- Renal dysfunction (CrCl <50 mL/min) — high-dose methotrexate (HD-MTX, ≥3 g/m²) backbone of all PCNSL 1L regimens contraindicated; transition to non-MTX regimen or refer to specialized center.RF-PCNSL-ORGAN-DYSFUNCTION
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
- High-dose methotrexate (≥1 g/m²) is renally cleared and depends on vigorous hydration + alkalinization for safe elimination. CrCl <50 mL/min causes catastrophic MTX accumulation, AKI worsening, mucositis, and myelotoxicity that can be fatal even with leucovorin and glucarpidase rescue.
CI-RENAL-FAILURE-FOR-HD-MTX
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-PCNSL-1L-R-MPV)
- Do not give steroids BEFORE biopsy.
- Do not give HD-MTX without monitoring CrCl + MTX levels.
- Do not administer vincristine intrathecally.
- Do not use full-dose WBRT (45 Gy) in >60 — severe neurocognitive decline.
Standard plan (IND-PCNSL-1L-MATRIX)
- Do not give steroids BEFORE diagnostic biopsy — they may destroy lymphoma morphology (false negative).
- Do not start HD-MTX without CrCl >50, normal hydration, leucovorin rescue, urine pH >7 — fatal AKI risk.
- Do not skip ophthalmology consult — ocular involvement ~20% may be silent.
- Do not give IT chemo routinely — CSF involvement is rare (~15%); IT only if CSF cytology+/positive flow.
- Do not administer vincristine (if in any supplementary regimen) intrathecally — fatal.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · R-MPV (Rituximab + HD-Methotrexate + Procarbazine + Vincristine), 5 cycles q14d
14-day cycles × 5-7 cycles induction; followed by HD-cytarabine consolidation OR reduced-dose WBRT 23.4 Gy для CR
Standard plan
Induction · MATRix (HD-Methotrexate + HD-Cytarabine + Thiotepa + Rituximab), 4 cycles
21-day cycles × 4 cycles induction; followed by autoSCT consolidation (BCNU + thiotepa)
MDT brief
Discussion questions (3, 1 blocking)
BLOCKING OQ-CD20-CONFIRMATION
Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated.
Anti-CD20 therapy is the backbone of most lines of treatment; absence of CD20 expression fully changes the regimen.
→ pathologist
OQ-STAGING-COMPLETE
Has complete staging been done (Lugano + PET/CT or CT)?
Prognosis and track selection depend on stage and tumor burden.
→ radiologist
OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist
MDT talk tree (4 steps)
| # | Owner | Topic | Action |
|---|
| 1 | pathologist | Pathology confirmation BLOCKING | Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated. |
| 2 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 3 | radiologist | Staging / disease burden | Has complete staging been done (Lugano + PET/CT or CT)? |
| 4 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
Skills (required) — mandatory virtual specialists (1)
Skills (recommended) — for consideration (2)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-CD20-CONFIRMATION
Data quality
Incomplete for MDT sign-off. MDT sign-off is incomplete until critical clinical data gaps are resolved.
- Biomarker coverage: 1/1 known (100%), 0 missing, 0 default-track gaps
- Missing critical: cd20_ihc_status, lugano_stage
- Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
- Unevaluated RedFlags: RF-PCNSL-HIGH-RISK-BIOLOGY, RF-PCNSL-INFECTION-SCREENING, RF-PCNSL-INTRACRANIAL-PRESSURE, RF-PCNSL-ORGAN-DYSFUNCTION, RF-PCNSL-TRANSFORMATION-PROGRESSION
Missing data for doctor action
| Priority | Clinical item | Owner | Why it matters | Next action | Blocks |
|---|
| CRITICAL | CD20 IHC status cd20_ihc_status
| pathologist | Confirms CD20-directed therapy is biologically appropriate. | Verify CD20 IHC result, specimen, method, and report date. | - |
| CRITICAL | Lugano stage lugano_stage
| radiologist | Defines lymphoma extent and supports tumor-burden and response-assessment decisions. | Document Lugano stage from PET/CT or contrast CT staging. | - |
| RECOMMENDED | LDH ratio to ULN ldh_ratio_to_uln
| medical_oncologist | Supports prognostic scoring and aggressive-biology flags. | Enter LDH with local upper limit of normal. | - |
| RECOMMENDED | FIB-4 liver fibrosis index fib4_index
| infectious_disease_hepatology | Screens hepatic fibrosis risk before hepatotoxic therapy or antiviral coordination. | Calculate FIB-4 from age, AST, ALT, and platelet count. | - |
| RECOMMENDED | PET/CT date pet_ct_date
| radiologist | Shows whether baseline staging is recent enough for treatment planning and later response comparison. | Document baseline PET/CT date or explain alternative staging modality. | - |
Technical MDT skill metadata (3/16 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 |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)
- SRC-NCCN-CNS-2025: NCCN Central Nervous System Cancers (v.3.2025)
Experimental options (clinical trials)
Last synced: 2026-05-13 · ctgov.
No active trials matched this scenario in ctgov.
Option availability in Ukraine
Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Aggressive plan R-MPV (Rituximab + HD-Methotrexate + Procarbazine + Vincristine), 5 cycles q14d (REG-R-MPV) 1/4 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Standard plan MATRix (HD-Methotrexate + HD-Cytarabine + Thiotepa + Rituximab), 4 cycles (REG-MATRIX) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-13.