OpenOnco · Treatment Plan

Treatment plan — DIS-B-ALL

PLAN-BMA-KMT2A_REARR_B_ALL-V1 · v1 · 2026-05-04

Patient

BMA-KMT2A_REARR_B_ALL · Algorithm: ALGO-B-ALL-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
BIO-KMT2A-REARRANGEMENT	KMT2A (MLL) rearrangement — any fusion partner; infant ALL (KMT2A-AFF1/AF4 most common ~80%) or adult B-ALL	IA	SRC-NCCN-ALL-2025: Level Category 2A (Supports, Sensitivity/Response)	Revumenib (menin inhibitor) FDA-approved (Nov 2024) for relapsed/refractory KMT2A-rearranged acute leukemia including B-ALL. AUGMENT-101 combined KMT2A-rearranged cohort (AML + ALL): ORR 23%, CR/CRh 18%. KMT2A rearrangement defines a high-risk B-ALL subset: in infants KMT2A-AFF1 is present in ~80% of infant B-ALL (EFS <30% with standard chemotherapy); in adults KMT2A-rearranged B-ALL is adverse-risk (NCCN/ELN). Revumenib represents a first targeted option for this historically chemotherapy-refractory population. Blinatumomab (CD19 BiTE, FDA-approved for R/R B-ALL) and inotuzumab ozogamicin are also active in KMT2A-rearranged B-ALL regardless of KMT2A status, but revumenib is the first mutation-specific approved agent. AlloHCT in CR remains the standard consolidation for eligible adults.	revumenib 163 mg PO BID monotherapy (dose-adjusted for CYP3A4 inhibitors to 95 mg BID) blinatumomab (independent of KMT2A status; CD19-targeted; R/R B-ALL per TOWER trial) inotuzumab ozogamicin (CD22-targeted; R/R B-ALL per INO-VATE trial)	SRC-NCCN-ALL-2025

Treatment options (2 tracks)

Aggressive plan

★ DEFAULT

Indication

IND-B-ALL-1L-PH-NEG

Regimen

Hyper-CVAD + Rituximab (CD20+) — alternating courses A/B, 8 cycles total

Drugs + NSZU

Alternating block A — block A (Hyper-CVAD): cyclophosphamide + vincristine + doxorubicin + dexamethasone — cycles 1, 3, 5, 7; with rituximab for CD20+ (cycles 1-4) and IT-CNS prophylaxis

Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 300 mg/m² q12h × 6 doses · IV days 1-3 (Course A only) · IV ⚠ NSZU — not for this indication
Vincristine (DRUG-VINCRISTINE) 2 mg flat dose · IV days 4 + 11 (Course A only) · IV ⚠ NSZU — not for this indication
Doxorubicin (DRUG-DOXORUBICIN) 50 mg/m² · IV day 4 (Course A only) · IV ⚠ NSZU — not for this indication
Dexamethasone (DRUG-DEXAMETHASONE) 40 mg · PO/IV days 1-4 + 11-14 (Course A only) · PO ⚠ NSZU — not for this indication
Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV days 1 + 11 (cycles 1-4 для CD20+ only) · IV ⚠ NSZU — not for this indication
Methotrexate (DRUG-METHOTREXATE) 12 mg IT · IT day 2 each cycle · IT ⚠ NSZU — not for this indication
Cytarabine (DRUG-CYTARABINE) 100 mg IT · IT day 8 each cycle · IT ⚠ NSZU — not for this indication

Alternating block B — block B (MA): high-dose methotrexate + HD-cytarabine — cycles 2, 4, 6, 8; with rituximab for CD20+ (cycles 1-4) and IT-CNS prophylaxis

Methotrexate (DRUG-METHOTREXATE) 1 g/m² · IV 24h infusion day 1 (Course B only); leucovorin rescue · IV ⚠ NSZU — not for this indication
Cytarabine (DRUG-CYTARABINE) 3 g/m² q12h × 4 doses · IV days 2-3 (Course B only) · IV ⚠ NSZU — not for this indication
Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV days 1 + 11 (cycles 1-4 для CD20+ only) · IV ⚠ NSZU — not for this indication
Methotrexate (DRUG-METHOTREXATE) 12 mg IT · IT day 2 each cycle · IT ⚠ NSZU — not for this indication
Cytarabine (DRUG-CYTARABINE) 100 mg IT · IT day 8 each cycle · IT ⚠ NSZU — not for this indication

Supportive care

SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-TLS-PROPHYLAXIS, SUP-GCSF-NEUTROPENIA, SUP-ANTIEMETIC-PREMED

Hard contraindications

CI-HBV-NO-PROPHYLAXIS, CI-LVEF-LOW-FOR-ANTHRACYCLINE

Reason

Engine default per algorithm ALGO-B-ALL-1L: {'step': 1, 'outcome': False, 'branch': {'result': 'IND-B-ALL-1L-PH-NEG'}, 'fired_red_flags': [], 'winner_red_flag': None}

Standard plan

Indication

IND-B-ALL-1L-PH-POS

Regimen

Hyper-CVAD + Rituximab (CD20+) — alternating courses A/B, 8 cycles total

Drugs + NSZU

Alternating block A — block A (Hyper-CVAD): cyclophosphamide + vincristine + doxorubicin + dexamethasone — cycles 1, 3, 5, 7; with rituximab for CD20+ (cycles 1-4) and IT-CNS prophylaxis

Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 300 mg/m² q12h × 6 doses · IV days 1-3 (Course A only) · IV ⚠ NSZU — not for this indication
Vincristine (DRUG-VINCRISTINE) 2 mg flat dose · IV days 4 + 11 (Course A only) · IV ⚠ NSZU — not for this indication
Doxorubicin (DRUG-DOXORUBICIN) 50 mg/m² · IV day 4 (Course A only) · IV ⚠ NSZU — not for this indication
Dexamethasone (DRUG-DEXAMETHASONE) 40 mg · PO/IV days 1-4 + 11-14 (Course A only) · PO ⚠ NSZU — not for this indication
Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV days 1 + 11 (cycles 1-4 для CD20+ only) · IV ⚠ NSZU — not for this indication
Methotrexate (DRUG-METHOTREXATE) 12 mg IT · IT day 2 each cycle · IT ⚠ NSZU — not for this indication
Cytarabine (DRUG-CYTARABINE) 100 mg IT · IT day 8 each cycle · IT ⚠ NSZU — not for this indication

Alternating block B — block B (MA): high-dose methotrexate + HD-cytarabine — cycles 2, 4, 6, 8; with rituximab for CD20+ (cycles 1-4) and IT-CNS prophylaxis

Methotrexate (DRUG-METHOTREXATE) 1 g/m² · IV 24h infusion day 1 (Course B only); leucovorin rescue · IV ⚠ NSZU — not for this indication
Cytarabine (DRUG-CYTARABINE) 3 g/m² q12h × 4 doses · IV days 2-3 (Course B only) · IV ⚠ NSZU — not for this indication
Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV days 1 + 11 (cycles 1-4 для CD20+ only) · IV ⚠ NSZU — not for this indication
Methotrexate (DRUG-METHOTREXATE) 12 mg IT · IT day 2 each cycle · IT ⚠ NSZU — not for this indication
Cytarabine (DRUG-CYTARABINE) 100 mg IT · IT day 8 each cycle · IT ⚠ NSZU — not for this indication

Supportive care

SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-TLS-PROPHYLAXIS, SUP-GCSF-NEUTROPENIA, SUP-ANTIEMETIC-PREMED

Hard contraindications

CI-HBV-NO-PROPHYLAXIS, CI-LVEF-LOW-FOR-ANTHRACYCLINE

Reason

Alternative track 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-BCR-ABL-JAK2	BCR-ABL + JAK2 + CALR + MPL	Critical	genomic	CSD Lab ✓ (code TBC)	all tracks
TEST-BM-ASPIRATE	Bone Marrow Aspirate	Critical	histology	—	all tracks
TEST-BM-TREPHINE	Bone Marrow Trephine	Critical	histology	—	all tracks
TEST-CBC	Complete Blood Count with Differential	Critical	lab	—	all tracks
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-COAG-PANEL	Coagulation 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-KARYOTYPE	Karyotype	Critical	genomic	CSD Lab ✓ (code TBC)	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-CSF-CYTOLOGY-FLOW	CSF cytology + flow cytometry	Standard	pathology	CSD Lab ✓ (code TBC)	all tracks
TEST-ECHO	Echocardiography	Standard	imaging	—	all tracks
TEST-PET-CT	FDG PET/CT (whole body)	Standard	imaging	—	all tracks
TEST-URIC-ACID	Serum Uric Acid	Standard	lab	—	all tracks
TEST-NGS-LYMPHOID-PANEL	Lymphoid NGS Panel	Desired	genomic	CSD Lab ✓ (code TBC)	all tracks

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

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
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.CI-LVEF-LOW-FOR-ANTHRACYCLINE

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Aggressive plan (IND-B-ALL-1L-PH-NEG)

Do not skip CNS prophylaxis.
Do not neglect MRD-monitoring post-induction — MRD+ pts receive blinatumomab.
Do not give vincristine intrathecally.
Do not start without HBV screen + entecavir prophylaxis (rituximab).
Do not neglect TLS prophylaxis in hyperleukocytosis (WBC >100K) — fatal hyperkalemia.

Standard plan (IND-B-ALL-1L-PH-POS)

Do not start without baseline BCR::ABL1 PCR — quantitative MRD drives therapy escalation.
Do not skip CNS prophylaxis (IT MTX/cytarabine + HD-MTX intercalated) — CNS relapse is fatal.
Do not neglect T315I mutation testing — imatinib/dasatinib are useless; ponatinib needed.
Do not give vincristine intrathecally — fatal.
Do not start TKI without ECG (QTc baseline) — TKIs prolong QT.
Do not reduce TKI dose without cause — under-dosing → resistance.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · Hyper-CVAD + Rituximab (CD20+)

21-day cycles × 8 alternating cycles (A/B/A/B/A/B/A/B); maintenance POMP × 30 months Ph-, або continuous TKI Ph+

MDT brief

Skills (recommended) — for consideration (1)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

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

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-ORGAN-DYSFUNCTION, RF-B-ALL-TRANSFORMATION-PROGRESSION, RF-BALL-CD22-POS-INO-CANDIDATE

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	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)

Experimental options (clinical trials)

Last synced: 2026-05-04 · 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 Hyper-CVAD + Rituximab (CD20+) — alternating courses A/B, 8 cycles total (REG-HYPER-CVAD-R)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Hyper-CVAD + Rituximab (CD20+) — alternating courses A/B, 8 cycles total (REG-HYPER-CVAD-R)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.

plan_id: PLAN-BMA-KMT2A_REARR_B_ALL-V1 | version: 1 | generated: 2026-05-04T14:13:16.612972+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): 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.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.