Patient
VAR-HGBL-DH-RELAPSED · Algorithm: ALGO-HGBL-DH-2L
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-HGBL-DH-2L-CART-AXICEL
- Regimen
- Axicabtagene ciloleucel (axi-cel CAR-T) for relapsed/refractory HGBL-DH
- Drugs + NSZU
Before main therapy: lymphodepletion — lymphocyte depletion before CAR-T to enable cell engraftment (Flu/Cy days -5 to -3 per ZUMA pattern)
- Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 500 mg/m²/day · IV days -5, -4, -3 (lymphodepletion) · IV ⚠ NSZU — not for this indication
- Fludarabine (DRUG-FLUDARABINE) 30 mg/m²/day · IV days -5, -4, -3 (lymphodepletion) · IV ⚠ NSZU — not for this indication
- Axicabtagene ciloleucel (DRUG-AXICABTAGENE-CILOLEUCEL) 2 × 10⁶ CAR+ T cells/kg (max 2 × 10⁸) · Single IV infusion after lymphodepletion (Flu/Cy days -5 to -3) · IV ✗ Not registered in UA
- Reason
- Primary current-line option selected by ALGO-HGBL-DH-2L at step 4.
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-B2-MICROGLOBULIN | Beta-2 Microglobulin | Standard | lab | — | all tracks |
| TEST-BRAIN-MRI-CONTRAST | Brain MRI with contrast | Standard | — | — | all tracks |
| TEST-ECHO | Echocardiography | Standard | imaging | — | all tracks |
| TEST-LN-CORE-BIOPSY | Core LN Biopsy | Standard | histology | — | all tracks |
| TEST-PET-CT | FDG PET/CT (whole body) | Standard | imaging | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Fit performance status (ECOG 0-1): patient is fully active or restricted in physically strenuous activity but ambulatory and able to carry out light work. Eligible for full-dose chemotherapy and intensive regimens (CHOEP, BEACOPP-escalated, HD-MTX, ASCT consolidation, CAR-T).
RF-FITNESS-ECOG-FIT
- Age >75 OR ECOG ≥3 — DA-EPOCH-R toxicity prohibitive; modified R-CHOP + IT MTX prophylaxis acceptable compromise.RF-HGBL-DH-FRAILTY-AGE
- MYC + BCL2 (and/or BCL6) rearrangement (double-/triple-hit) confirmed by FISH — DA-EPOCH-R + IT methotrexate prophylaxis preferred over R-CHOP per multiple retrospective and small prospective series.RF-HGBL-DH-HIGH-RISK-BIOLOGY
- HBV/HCV/HIV serology mandatory pre-rituximab; HIV-associated HGBL-DH gets cART optimization concurrently with chemo.RF-HGBL-DH-INFECTION-SCREENING
- Cardiac dysfunction (LVEF <50%) — DA-EPOCH-R (preferred for HGBL-DH/-TH) is anthracycline-intensive; cardio-onc consult and dose-modification required.RF-HGBL-DH-ORGAN-DYSFUNCTION
- PET-2 progression (Deauville 4-5 with new lesions) or end-of-induction non-CR — HGBL-DH refractory disease has very poor outcomes; CAR-T (axi-cel/liso-cel) preferred over salvage chemo.RF-HGBL-DH-TRANSFORMATION-PROGRESSION
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-HGBL-DH-2L-CART-AXICEL)
- Do not initiate without CAR-T-certified center referral pathway — toxicity management requires specialized infrastructure.
- Do not prescribe with ECOG >1 OR active CNS involvement — exclusion criteria CAR-T trials.
- Do not skip baseline PET + brain MRI — high CNS relapse risk in HGBL-DH.
- Do not forget about bridging therapy between apheresis + infusion — disease control critical.
- Do not ignore CRS / ICANS monitoring during the first 14 days post-infusion.
- Do not prescribe in patients with active autoimmune disease.
Monitoring schedule
Monitoring schedule by treatment phase
Aggressive plan · MON-RITUXIMAB-MONO
| Phase | Window | Tests | Checkpoints |
|---|
| baseline | Within 2 weeks before first dose | TEST-CBC, TEST-LFT, TEST-LDH, TEST-CD20-IHC, TEST-HBV-SEROLOGY, TEST-HCV-ANTIBODY, TEST-FLOW-CYTOMETRY | - Confirm CD20+ histology
- HBV status + entecavir prophylaxis if HBsAg+ or anti-HBc+
|
| induction | Day 1 of each weekly induction × 4 | TEST-CBC, TEST-LFT | - Infusion reactions especially first dose
|
| maintenance | Every 2 months × 2 years | TEST-CBC, TEST-LFT, TEST-LDH | - HBV-DNA quarterly during therapy and 12 mo post
- Disease assessment clinically; imaging if concern
|
| follow_up | Every 6 months × 5 years post-treatment | TEST-CBC, TEST-LFT, TEST-LDH | - Surveillance for relapse + transformation
|
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Baseline
Within 2 weeks before first dose
Induction · Axicabtagene ciloleucel (axi-cel CAR-T) for relapsed/refractory HGBL-DH
1-day cycles × Single infusion
Maintenance
Every 2 months × 2 years
Follow-up
Every 6 months × 5 years post-treatment
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-HGBL-DH-CNS-PROPHYLAXIS-TRIGGER, RF-HGBL-DH-EMERGENCY-TLS, RF-HGBL-DH-HIGH-RISK-BIOLOGY, RF-HGBL-DH-ORGAN-DYSFUNCTION, RF-HGBL-DH-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-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-ZUMA-1-NEELAPU-2017: Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma (2017)
- SRC-ZUMA-7-LOCKE-2022: Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma (2022)
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 Axicabtagene ciloleucel (axi-cel CAR-T) for relapsed/refractory HGBL-DH (REG-CAR-T-AXICEL-HGBL) 1/3 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-13.