OpenOnco · DIS-B-ALL · Actionable biomarker present
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OpenOnco · Treatment Plan
Treatment plan — B-Lymphoblastic Leukemia/Lymphoma
PLAN-VAR-B-ALL-BIOMARK-V1 · v1 · 2026-06-27
Patient
VAR-B-ALL-BIOMARK · Algorithm: ALGO-B-ALL-1L
DiagnosisB-Lymphoblastic Leukemia/Lymphoma
MOH / ICD-10C91.0
ICD-O-39811/3

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
No clinically actionable variants matched in this profile.

Primary current-line option

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
Primary current-line option selected by ALGO-B-ALL-1L at step 1.

Other current-line alternatives (1 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
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
Current-line alternative presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks
IDNamePriorityCategoryWhere to orderNeeded for
TEST-BCR-ABL-JAK2BCR-ABL + JAK2 + CALR + MPLCriticalgenomicCSD Lab ✓ (code TBC)all tracks
TEST-BM-ASPIRATEBone Marrow AspirateCriticalhistologyall tracks
TEST-BM-TREPHINEBone Marrow TrephineCriticalhistologyall tracks
TEST-CBCComplete Blood Count with DifferentialCriticallaball tracks
TEST-CMPComprehensive Metabolic PanelCriticallaball tracks
TEST-COAG-PANELCoagulation PanelCriticallaball tracks
TEST-FISH-PANELFISH (Fluorescence In Situ Hybridization)CriticalgenomicCSD Lab ✓ (code TBC)all tracks
TEST-FLOW-CYTOMETRYFlow CytometryCriticalhistologyCSD Lab ✓ (code TBC)all tracks
TEST-HBV-SEROLOGYHepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs)Criticallaball tracks
TEST-HCV-ANTIBODYHCV AntibodyCriticallaball tracks
TEST-HIV-SEROLOGYHIV Antibody/AntigenCriticallaball tracks
TEST-KARYOTYPEKaryotypeCriticalgenomicCSD Lab ✓ (code TBC)all tracks
TEST-LDHLactate DehydrogenaseCriticallaball tracks
TEST-LFTLiver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)Criticallaball tracks
TEST-PREGNANCYBeta-HCGCriticallaball tracks
TEST-CSF-CYTOLOGY-FLOWCSF cytology + flow cytometryStandardpathologyCSD Lab ✓ (code TBC)all tracks
TEST-ECHOEchocardiographyStandardimagingall tracks
TEST-PET-CTFDG PET/CT (whole body)Standardimagingall tracks
TEST-URIC-ACIDSerum Uric AcidStandardlaball tracks
TEST-NGS-LYMPHOID-PANELLymphoid NGS PanelDesiredgenomicCSD 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+) — alternating courses A/B, 8 cycles total
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

Discussion questions (1, 0 blocking)

MDT talk tree (2 steps)

#OwnerTopicAction
1hematologistStaging / disease burden What is the current LDH? Marker of tumor burden and transformation.
2clinical_pharmacistSpecialist review Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (recommended) — for consideration (1)

  • Clinical pharmacist recommended
    Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Data quality

Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.
  • Biomarker coverage: 0/0 known (100%), 0 missing, 0 default-track gaps
  • 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
Technical MDT skill metadata (1/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
Specialistskill_idVersionLast reviewedSign-offsDomain
Cellular therapy specialist (CAR-T)cellular_therapy_specialistv0.1.02026-04-250cellular_therapy
Clinical pharmacistclinical_pharmacistv0.1.02026-04-250clinical_pharmacy
Hematologist / oncohematologisthematologistv0.1.02026-04-250hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)hematopathologistv0.1.02026-04-250hematopathology
Infectious disease / hepatologyinfectious_disease_hepatologyv0.1.02026-04-250infectious_diseases
Medical oncologist (solid-tumor chemotherapist)medical_oncologistv0.1.02026-04-250solid_oncology
Molecular geneticist / molecular oncologistmolecular_geneticistv0.1.02026-04-250molecular_oncology
Palliative carepalliative_carev0.1.02026-04-250palliative_care
Pathologist (general)pathologistv0.1.02026-04-250pathology
Primary care / family physicianprimary_carev0.1.02026-04-250primary_care
Psycho-oncologistpsychologistv0.1.02026-04-250psychosocial
Radiation oncologistradiation_oncologistv0.1.02026-04-250radiation_oncology
Radiologistradiologistv0.1.02026-04-250diagnostic_imaging
Social worker / case managersocial_worker_case_managerv0.1.02026-04-250psychosocial
Surgical oncologistsurgical_oncologistv0.1.02026-04-250surgical_oncology
Transplant specialist (BMT)transplant_specialistv0.1.02026-04-250cellular_therapy

Sources cited

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: 2026-06-27.
NCTTitlePhaseStatusSponsorUASignalsEligibility (excerpt)
NCT07502118NexCAR19 (Talikabtagene Autoleucel) in Relapsed/Refractory B-Cell Malignancies (NexCAR19)PHASE2 / PHASE3RECRUITINGHealth Institutes of TurkeySmall N (<50) Surrogate endpoint only Single country
NCT04532268A Study of Humanized CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell ALL and B-cell NHLEARLY_PHASE1RECRUITINGZhejiang UniversitySingle country
NCT04195633Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological MalignanciesPHASE2RECRUITINGFred Hutchinson Cancer CenterSingle country
NCT04941716Acalabrutinib in Combination With Venetoclax for the Treatment of Refractory or Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma, The AVENUE-2 TrialPHASE2RECRUITINGFred Hutchinson Cancer CenterSmall N (<50) Single country
NCT05082519Caloric Restriction and Activity to Reduce Chemoresistance in B-ALLPHASE2RECRUITINGEtan OrgelSingle country
NCT04544592UCD19 CarT in Treatment of Pediatric B-ALL and B-NHLPHASE1 / PHASE2RECRUITINGUniversity of Colorado, DenverSmall N (<50) Single country
NCT04546399A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)PHASE2RECRUITINGNational Cancer Institute (NCI)
NCT07671378A Study of MRD-Guided Zanubrutinib Plus Sonrotoclax in Treatment-Naïve, High-Risk CLL/SLL PatientsPHASE2RECRUITINGThe First Affiliated Hospital with Nanjing Medical UniversitySmall N (<50) Single country
NCT06696833Allogeneic CD19-targeted CAR-γδT Cell Infusion Therapy in Relapsed/Refractory B Cell Acute Lymphoblastic LeukemiaEARLY_PHASE1RECRUITINGThe First Affiliated Hospital of Soochow UniversitySmall N (<50) Single country
NCT00923507Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)N/ARECRUITINGNational Heart, Lung, and Blood Institute (NHLBI)Single country

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).
OptionUA registrationNSZUCost orientationAccess pathway
Aggressive plan
Hyper-CVAD + Rituximab (CD20+) — alternating courses A/B, 8 cycles total (REG-HYPER-CVAD-R)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Standard plan
Hyper-CVAD + Rituximab (CD20+) — alternating courses A/B, 8 cycles total (REG-HYPER-CVAD-R)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Trial · NCT07502118
NexCAR19 (Talikabtagene Autoleucel) in Relapsed/Refractory B-Cell Malignancies (NexCAR19)
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04532268
A Study of Humanized CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell ALL and B-cell NHL
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04195633
Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04941716
Acalabrutinib in Combination With Venetoclax for the Treatment of Refractory or Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma, The AVENUE-2 Trial
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT05082519
Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04544592
UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT04546399
A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT07671378
A Study of MRD-Guided Zanubrutinib Plus Sonrotoclax in Treatment-Naïve, High-Risk CLL/SLL Patients
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT06696833
Allogeneic CD19-targeted CAR-γδT Cell Infusion Therapy in Relapsed/Refractory B Cell Acute Lymphoblastic Leukemia
No UA site listed — international referral required
— unknown— unknown
self-pay: ₴0/course
Trial sponsor
Trial · NCT00923507
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
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: 2026-06-27.