Patient
VAR-BURKITT-RELAPSED · Algorithm: ALGO-BURKITT-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-BURKITT-2L-RICE-ASCT
- Regimen
- R-ICE (Rituximab + Ifosfamide + Carboplatin + Etoposide) × 2-3 cycles → ASCT in CR2 (r/r Burkitt salvage)
- Drugs + NSZU
Salvage induction — salvage induction R-ICE × 2-3 cycles — ifosfamide + carboplatin + etoposide with rituximab for r/r Burkitt before ASCT
- Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 of each 14-day cycle × 2-3 · IV ⚠ NSZU — not for this indication
- Ifosfamide (DRUG-IFOSFAMIDE) 5 g/m² · IV continuous 24h day 2; mesna co-administration · IV ⚠ NSZU — not for this indication
- Carboplatin (DRUG-CARBOPLATIN) AUC 5 (max 800 mg) · IV day 2 · IV ⚠ NSZU — not for this indication
- Etoposide (DRUG-ETOPOSIDE) 100 mg/m² · IV days 1-3 · IV ⚠ NSZU — not for this indication
- Methotrexate (DRUG-METHOTREXATE) 12 mg IT · IT each cycle (CNS prophylaxis / treatment) · IT ⚠ NSZU — not for this indication
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-TLS-PROPHYLAXIS, SUP-GCSF-NEUTROPENIA, SUP-ANTIEMETIC-PREMED, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS, CI-RENAL-FAILURE-FOR-HD-MTX
- Reason
- Primary current-line option selected by ALGO-BURKITT-2L at step 4.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-BURKITT-2L-RDHAP-ASCT
- Regimen
- R-DHAP (Rituximab + Dexamethasone + HD-Cytarabine + Cisplatin) × 2-3 cycles → ASCT/alloSCT (r/r Burkitt salvage; non-cross-resistant alternative to R-ICE)
- Drugs + NSZU
Salvage induction — salvage induction R-DHAP × 2-3 cycles — cisplatin + HiDAC + steroid for r/r Burkitt before transplant consolidation
- Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 of each cycle · IV ⚠ NSZU — not for this indication
- Dexamethasone (DRUG-DEXAMETHASONE) 40 mg · IV/PO days 1-4 each cycle · IV ⚠ NSZU — not for this indication
- Cytarabine (DRUG-CYTARABINE) 2 g/m² q12h × 2 doses · IV day 2 each cycle (HiDAC component) · IV ⚠ NSZU — not for this indication
- Cisplatin (DRUG-CISPLATIN) 100 mg/m² · IV continuous 24h day 1 each cycle · IV ⚠ NSZU — not for this indication
- Methotrexate (DRUG-METHOTREXATE) 12 mg IT · IT each cycle (CNS prophylaxis / treatment) · IT ⚠ NSZU — not for this indication
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-TLS-PROPHYLAXIS, SUP-GCSF-NEUTROPENIA, SUP-ANTIEMETIC-PREMED, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS, CI-RENAL-FAILURE-FOR-HD-MTX
- Reason
- Current-line alternative presented for HCP consideration
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-BM-ASPIRATE | Bone Marrow Aspirate | Critical | histology | — | all tracks |
| 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-FISH-PANEL | FISH (Fluorescence In Situ Hybridization) | Critical | genomic | CSD Lab ✓ (code TBC) | all tracks |
| TEST-FLOW-CYTOMETRY | Flow Cytometry | Critical | histology | CSD Lab ✓ (code TBC) | 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 | — | all tracks |
| TEST-RENAL-FUNCTION-EGFR | Renal function with eGFR | Critical | lab | — | all tracks |
| TEST-WHOLE-BODY-MRI | Whole-Body MRI | Critical | imaging | — | all tracks |
| TEST-CMV-SEROLOGY | CMV IgG/IgM | Standard | lab | — | all tracks |
| TEST-CSF-CYTOLOGY-FLOW | CSF cytology + flow cytometry | Standard | pathology | CSD Lab ✓ (code TBC) | 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 |
| TEST-URIC-ACID | Serum Uric Acid | Standard | lab | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Frailty profile precluding intensive Burkitt regimens (CODOX-M/IVAC or DA-EPOCH-R full-dose): ECOG ≥3, OR (age ≥65 with G8 ≤14), OR composite frailty (age ≥70 + Charlson ≥3). Triggers de-escalation to attenuated R-mini-CHOP-like regimen or palliative R-CHOP — Burkitt curability dramatically lower in frail elderly.
RF-BURKITT-FRAILTY-AGE
- Ifosfamide contraindicated or high-risk in relapsed/refractory Burkitt lymphoma 2L salvage, routing to R-DHAP (cisplatin-based) over R-ICE (ifosfamide-based). Three clinical scenarios: (1) Prior hemorrhagic cystitis — any prior ifosfamide- or cyclophosphamide-related hemorrhagic cystitis is a contraindication to further ifosfamide even with mesna; residual mucosal damage increases bleeding risk; (2) Pelvic RT field overlap — prior irradiation to bladder field dramatically increases ifosfamide-related bladder toxicity; avoid; (3) Pre-existing peripheral neuropathy grade ≥2 — ifosfamide causes both peripheral and central neuropathy; additional neurotoxicity risk unacceptable when baseline neuropathy already impairs function; (4) Bladder outlet obstruction, single kidney, or other bladder structural contraindication to mesna- protected ifosfamide. In these scenarios R-DHAP (dexamethasone 40 mg d1-4 + cytarabine 2 g/m² q12h d2 + cisplatin 100 mg/m² d1) is the preferred platinum salvage — equivalent salvage activity to R-ICE (CORAL trial subgroup) with different toxicity profile (renal/ototoxicity from cisplatin vs bladder/neuropathy from ifosfamide).
RF-BURKITT-IFOS-CONTRAINDICATED
- Active or latent infection requiring resolution / prophylaxis before initiating DA-EPOCH-R or CODOX-M/IVAC in Burkitt: HBsAg-positive (mandatory anti-CD20 → high HBV reactivation risk), anti-HBc-positive (occult HBV), HCV-RNA-positive, HIV-positive (high prevalence in Burkitt — endemic and sporadic), or active TB. EBV testing recommended (endemic Burkitt EBV-driven; informs prognostication).
RF-BURKITT-INFECTION-SCREENING
- Baseline organ dysfunction precluding HD-MTX-containing CODOX-M/IVAC or full-dose DA-EPOCH-R in Burkitt lymphoma: CrCl <50 (HD-methotrexate contraindicated, Burkitt CNS-prophylaxis-mandatory disease), LVEF <50% (anthracycline contraindicated), bilirubin >3× ULN (vincristine / doxorubicin / methotrexate metabolism), or pulmonary DLCO <60%.
RF-BURKITT-ORGAN-DYSFUNCTION
- Burkitt primary-refractory (no CR after 2 cycles induction) OR early relapse <6 months post-induction OR rapidly progressive disease during pre-phase corticosteroids — extremely poor prognosis subset; routes to intensive salvage (R-ICE, R-IVAC) with auto/alloSCT bridge intent or CD19 CAR-T trial enrollment.
RF-BURKITT-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
- 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
- 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-BURKITT-2L-RICE-ASCT)
- Do NOT delay intervention — natural history of relapsed Burkitt is catastrophic (3-6 months OS untreated).
- Do NOT skip CSF cytology + flow at relapse — CNS disease ≥30% at relapse; IT therapy mandatory.
- Do NOT forget rasburicase for TLS prophylaxis cycle 1 — TLS may be fatal on rapid response.
- Do NOT skip mesna at 100% of ifosfamide dose — hemorrhagic cystitis risk is fatal without mesna.
- Do NOT ignore ifosfamide encephalopathy (altered mental status) — discontinue immediately + methylene blue 50 mg IV q4-6h.
- Do NOT skip CrCl + cardiac (LVEF) + pulmonary fitness pre-ASCT.
- Do NOT start ASCT at PR (not CR) — outcomes substantially worse; salvage spillover to CR2 first OR alloSCT consideration.
- Do NOT skip HBV screening + entecavir prophylaxis.
- Do NOT forget pre-transplant viral PCRs (CMV / HBV / HCV / HIV) + donor pre-typing for potential alloSCT.
Aggressive plan (IND-BURKITT-2L-RDHAP-ASCT)
- Do NOT delay intervention — natural history of relapsed Burkitt is catastrophic.
- Do NOT skip CSF cytology + flow at relapse — CNS disease ≥30% at relapse.
- Do NOT forget IV hydration + diuresis for cisplatin nephroprotection (mannitol if needed).
- Do NOT ignore pre-existing peripheral neuropathy — Grade ≥2 = switch to R-ICE.
- Do NOT skip baseline + serial audiology — cisplatin ototoxicity may be permanent.
- Do NOT ignore cerebellar toxicity from HiDAC (ataxia, dysmetria) — discontinue immediately; permanent if Grade ≥2.
- Do NOT skip cytarabine eye drops + cerebellar exam baseline + each HiDAC dose.
- Do NOT start ASCT at PR — outcomes substantially worse; salvage spillover to CR2 first.
- Do NOT forget rasburicase for TLS prophylaxis cycle 1 — TLS may be fatal.
- Do NOT skip HBV screening + entecavir prophylaxis.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · R-ICE (Rituximab + Ifosfamide + Carboplatin + Etoposide) × 2-3 cycles → ASCT in CR2 (r/r Burkitt salvage)
14-day cycles × 2-3 cycles induction → restage by PET-CT → BEAM-conditioned ASCT in CR2 (fit transplant-eligible) OR alloSCT (refractory after R-ICE)
Aggressive plan
Induction · R-DHAP (Rituximab + Dexamethasone + HD-Cytarabine + Cisplatin) × 2-3 cycles → ASCT/alloSCT (r/r Burkitt salvage; non-cross-resistant alternative to R-ICE)
21-day cycles × 2-3 cycles induction → restage by PET-CT → ASCT in CR2 (fit transplant-eligible) OR alloSCT (refractory)
MDT brief
Discussion questions (4, 2 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
BLOCKING OQ-BIOMARKER-MYC-REARRANGEMENT
What is the status of MYC rearrangement (8q24) by FISH break-apart (BIO-MYC-REARRANGEMENT)? It is required by track(s): IND-BURKITT-2L-RICE-ASCT, IND-BURKITT-2L-RDHAP-ASCT. Expected value: positive (Burkitt-defining).
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.
→ molecular_geneticist
MDT talk tree (5 steps)
| # | Owner | Topic | Action |
|---|
| 1 | molecular_geneticist | Biomarker status BLOCKING | What is the status of MYC rearrangement (8q24) by FISH break-apart (BIO-MYC-REARRANGEMENT)? It is required by track(s): IND-BURKITT-2L-RICE-ASCT, IND-BURKITT-2L-RDHAP-ASCT. Expected value: positive (Burkitt-defining). |
| 2 | pathologist | Pathology confirmation BLOCKING | Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated. |
| 3 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 4 | radiologist | Staging / disease burden | Has complete staging been done (Lugano + PET/CT or CT)? |
| 5 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
Skills (required) — mandatory virtual specialists (1)
Skills (recommended) — for consideration (3)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Owns: OQ-BIOMARKER-MYC-REARRANGEMENT
- Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-CD20-CONFIRMATION
Data quality
Incomplete for default-track review. Default-track review is incomplete until required biomarker gaps are resolved.
- Biomarker coverage: 1/2 known (50%), 1 missing, 1 default-track gaps
- Missing critical: cd20_ihc_status, lugano_stage
- Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
- Unevaluated RedFlags: RF-BURKITT-EMERGENCY-TLS, RF-BURKITT-FRAILTY-AGE, RF-BURKITT-HIGH-RISK, RF-BURKITT-IFOS-CONTRAINDICATED, RF-BURKITT-INFECTION-SCREENING, RF-BURKITT-ORGAN-DYSFUNCTION, RF-BURKITT-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. | - |
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-MYC-REARRANGEMENT | MYC rearrangement (8q24) by FISH break-apart | molecular_geneticist | yes | IND-BURKITT-2L-RICE-ASCT, IND-BURKITT-2L-RDHAP-ASCT | Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive (Burkitt-defining) |
Technical MDT skill metadata (4/16 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)
Experimental options (clinical trials)
Last synced: 2026-05-12 · 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-ICE (Rituximab + Ifosfamide + Carboplatin + Etoposide) × 2-3 cycles → ASCT in CR2 (r/r Burkitt salvage) (REG-RICE-BURKITT) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan R-DHAP (Rituximab + Dexamethasone + HD-Cytarabine + Cisplatin) × 2-3 cycles → ASCT/alloSCT (r/r Burkitt salvage; non-cross-resistant alternative to R-ICE) (REG-RDHAP-BURKITT) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-12.