OpenOnco · Treatment Plan

Treatment plan — DIS-B-ALL

PLAN-BMA-BCR_ABL1_F317L_BALL-V1 · v1 · 2026-05-04

Patient

BMA-BCR_ABL1_F317L_BALL · Algorithm: ALGO-B-ALL-2L

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
No clinically actionable variants matched in this profile.

⚠️ Not included in plan

Biomarker	Status
BIO-BCR-ABL1	Not in KB — ask clinician to verify

Treatment options (3 tracks)

Aggressive plan

★ DEFAULT

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}

Aggressive plan

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

Aggressive plan

Indication

IND-B-ALL-3L-TISAGENLECLEUCEL

Regimen

Tisagenlecleucel CD19 CAR-T for R/R B-ALL ≤25 years

Drugs + NSZU

Before main therapy: lymphodepletion — lymphocyte depletion before CAR-T to enable cell engraftment (ELIANA-style: Flu × 4 days + Cy × 2 days)

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	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-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-IMMUNOGLOBULINS	Quantitative Immunoglobulins	Standard	lab	—	all tracks
TEST-MRI-BRAIN-CONTRAST	MRI brain with contrast	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

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)

Do NOT start without CD19 confirmation — CD19-negative blasts evade targeting; ~30% relapse-loss CD19.
Do NOT start without cytoreduction with BM blasts >50% OR PB blasts >15K — TLS + CRS risk amplified.
Do NOT ignore CRS / neurotox surveillance — hospitalization is mandatory cycle 1 d1-9, cycle 2 d1-2.
Do NOT use without on-site tocilizumab (≥2 dose) — fatal CRS possible.
Do NOT continue with Grade ≥3 recurrent neurotoxicity OR seizures — permanent discontinuation.
Do NOT prescribe prophylactic systemic corticosteroids beyond dexamethasone premedication — suppresses T-cell engagement + reduces efficacy.
Do NOT forget the alloHCT-pathway for transplant-eligible — single-agent blinatumomab not curative for R/R.

Aggressive plan (IND-B-ALL-2L-INOTUZUMAB)

Do NOT use with confirmed history of severe VOD/SOS — absolute CI.
Do NOT exceed 2 cycles pre-HCT — VOD risk is cumulative (boxed warning).
Do NOT use dual-alkylator (Bu/Cy) conditioning post-inotuzumab — Bu/Flu is preferred.
Do NOT ignore baseline + per-cycle LFT (bilirubin, ALT, AST) — hepatotoxicity is a prelude to VOD.
Do NOT start without CD22 confirmation — CD22-negative blasts evade targeting.
Do NOT forget TLS prophylaxis (allopurinol + hydration) — particularly cycle 1.
Do NOT forget the alloHCT-pathway — single-agent inotuzumab is NOT curative.

Aggressive plan (IND-B-ALL-3L-TISAGENLECLEUCEL)

Do NOT prescribe prophylactic systemic corticosteroids — suppresses CAR-T expansion + reduces efficacy.
Do NOT start without on-site tocilizumab (minimum 2 doses) BEFORE infusion — fatal CRS possible.
Do NOT do this in a center without CAR-T accreditation (FACT/JACIE/REMS) — toxicity management requires a specialized team + ICU access.
Do NOT skip baseline brain MRI — CNS-2/3 with symptoms is an ELIANA exclusion; risk of fatal ICANS is higher.
Do NOT ignore temporary bridging chemotherapy (3-4 week manufacturing window) — disease progression in this window reduces efficacy + may make patient unfit for CAR-T.
Do NOT prescribe with active uncontrolled infection — lymphodepletion + CRS = high mortality.
Do NOT forget IVIG for long-lasting hypogammaglobulinemia (IgG <400 + recurrent infections) — B-cell aplasia may last >12 months.

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)

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-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)

Experimental options (clinical trials)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-04.

NCT	Title	Phase	Status	Sponsor	UA
NCT04872790	Venetoclax, Dasatinib, Prednisone, Rituximab and Blinatumomab for the Treatment of Newly Diagnosed or Relapsed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia	PHASE1	RECRUITING	OHSU Knight Cancer Institute	—
NCT03984968	CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia	PHASE1 / PHASE2	RECRUITING	The First Affiliated Hospital of Soochow University	—
NCT06173518	A Study of CD19 Targeted CAR T Cell Therapy in Pediatric Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B-cell Non-Hodgkin Lymphoma (B NHL)	PHASE1	RECRUITING	Autolus Limited	—
NCT06503094	CD19 & CD20 Bispecific CAR T Cells for Relapsed / Refractory B Cell Hematological Tumors	PHASE1 / PHASE2	RECRUITING	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	—
NCT03676504	Treatment of Patients With Relapsed or Refractory CD19+ Lymphoid Disease With T Cells Expressing a Third-generation CAR	PHASE1 / PHASE2	RECRUITING	University Hospital Heidelberg	—
NCT03150693	Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia	PHASE3	RECRUITING	Alliance for Clinical Trials in Oncology	—
NCT05157971	Venetoclax and a Pediatric-Inspired Regimen for the Treatment of Newly Diagnosed B Cell Acute Lymphoblastic Leukemia	PHASE1	RECRUITING	City of Hope Medical Center	—
NCT06943872	A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL)	PHASE3	RECRUITING	BeOne Medicines	—
NCT05602363	AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma	PHASE1	RECRUITING	Carna Biosciences, Inc.	—
NCT06863259	Study of Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone for Relapsed B-cell ALL	PHASE1	RECRUITING	Children's Hospital Medical Center, Cincinnati	—

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

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 Blinatumomab BiTE for MRD+ post-induction OR R/R B-ALL (REG-BLINATUMOMAB-B-ALL)	✓ registered	✓ covered	₴-? — verify pathway	NSZU 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	✗ not registered	✗ 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	✗ not registered	✗ out-of-pocket	₴-? — verify pathway	not recorded
Trial · NCT04872790 Venetoclax, Dasatinib, Prednisone, Rituximab and Blinatumomab for the Treatment of Newly Diagnosed or Relapsed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT03984968 CD19 CAR-T Consolidation Therapy for Acute Lymphoblastic Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06173518 A Study of CD19 Targeted CAR T Cell Therapy in Pediatric Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B-cell Non-Hodgkin Lymphoma (B NHL) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06503094 CD19 & CD20 Bispecific CAR T Cells for Relapsed / Refractory B Cell Hematological Tumors No UA site listed — international referral required	— unknown	— unknown	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	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT03150693 Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05157971 Venetoclax and a Pediatric-Inspired Regimen for the Treatment of Newly Diagnosed B Cell Acute Lymphoblastic Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06943872 A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL) No UA site listed — international referral required	— unknown	— unknown	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	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06863259 Study of Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone for Relapsed B-cell ALL No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor

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

plan_id: PLAN-BMA-BCR_ABL1_F317L_BALL-V1 | version: 1 | generated: 2026-05-04T14:13:16.579155+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.