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OpenOnco · DIS-ATLL · BIO-JAK3 (ESCAT IIA)
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Treatment plan — DIS-ATLL
PLAN-BMA-JAK3_ATLL-V1 · v1 · 2026-05-04
Patient
BMA-JAK3_ATLL · Algorithm: ALGO-ATLL-1L

Etiological driver

Etiological driver · etiologically_driven archetype
Adult T-Cell Leukemia/Lymphoma
  • HTLV-1 (Human T-cell Lymphotropic Virus 1) — defining etiology, 100%
  • CD3+ CD4+ CD25+ CCR4+ FoxP3+ — Treg-like phenotype
  • TCR αβ rearrangement з clonal HTLV-1 integration
  • Endemic у Japan, Caribbean, Latin America, Sub-Saharan Africa

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks
BiomarkerVariantESCATEvidenceClinical significanceDrugsSources
BIO-JAK3JAK3 activating mutation (A572V, A573V, M511I most common) — adult T-cell leukemia/lymphoma (ATLL); predominantly aggressive subtypes (acute and lymphoma)IIA
  • SRC-ESMO-PTCL-2024: Level B (Supports, Sensitivity/Response)
JAK3 activating mutations are detected in ~35% of aggressive ATLL subtypes (acute and lymphoma types) and activate downstream STAT3/STAT5 independent of cytokine stimulation. Ruxolitinib (JAK1/2 inhibitor; FDA-approved for myelofibrosis, PV, GVHD, CTCL) has documented activity in JAK3-mutant ATLL: case series and retrospective analyses report ORRs of 40–67% in relapsed/refractory ATLL; single-arm phase II data is limited. No FDA approval for ATLL specifically. Mogamulizumab (anti-CCR4, FDA 2018 for CTCL) is approved for relapsed/refractory CTCL and ATLL in Japan; FDA approval is CTCL only in US — CCR4 expression is present in ~90% of ATLL independent of JAK3 status. JAK3 mutation confers worse prognosis in ATLL and identifies a subset potentially responsive to JAK pathway inhibition. ESCAT IIA: biomarker predicts response to an investigational (in ATLL context) therapy class (JAK inhibitors).ruxolitinib 20 mg PO BID (investigational in ATLL; dose per MF/GVHD approval; JAK3-mutant subset; clinical trial preferred)
mogamulizumab 1 mg/kg IV (approved for CTCL in US; used off-label for ATLL; CCR4-targeted, not JAK3-specific)
VCAP-AMP-VECP chemotherapy (standard aggressive ATLL per Japanese guidelines)
  • SRC-ESMO-PTCL-2024

Treatment options (2 tracks)

Aggressive plan
★ DEFAULT
Indication
IND-ATLL-1L-AGGRESSIVE
Regimen
CHOEP (cyclophosphamide + doxorubicin + vincristine + etoposide + prednisone), 6 cycles
Drugs + NSZU
  • Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 750 mg/m² · IV day 1 each 21-day cycle · IV ⚠ NSZU — not for this indication
  • Doxorubicin (DRUG-DOXORUBICIN) 50 mg/m² · IV day 1 each cycle · IV ⚠ NSZU — not for this indication
  • Vincristine (DRUG-VINCRISTINE) 1.4 mg/m² (cap 2 mg) · IV day 1 each cycle · IV ⚠ NSZU — not for this indication
  • Etoposide (DRUG-ETOPOSIDE) 100 mg/m² · IV days 1-3 each cycle · IV ⚠ NSZU — not for this indication
  • Prednisone (DRUG-PREDNISONE) 100 mg · PO days 1-5 each cycle · PO ⚠ NSZU — not for this indication
Supportive care
SUP-PJP-PROPHYLAXIS, SUP-ANTIEMETIC-PREMED, SUP-GCSF-NEUTROPENIA
Hard contraindications
CI-LVEF-LOW-FOR-ANTHRACYCLINE
Reason
Engine default per algorithm ALGO-ATLL-1L: {'step': 2, 'outcome': False, 'branch': {'result': 'IND-ATLL-1L-AGGRESSIVE'}, 'fired_red_flags': [], 'winner_red_flag': None}
Standard plan
Indication
IND-ATLL-1L-INDOLENT-AZT-IFN
Regimen
AZT (zidovudine) + IFN-α — continuous, dose-adjusted
Drugs + NSZU
  • Zidovudine (DRUG-ZIDOVUDINE) 1.5-3 g/day divided BID-TID · PO continuous, dose-adjust по hematologic toxicity · PO ✓ NSZU covered
  • Interferon alfa (DRUG-INTERFERON-ALPHA) 5 MIU/m² SC daily для induction; 5 MIU/m² 3×/тиждень maintenance · SC daily induction, 3×/тиждень maintenance · SC ✓ NSZU covered
Supportive care
SUP-PSYCH-MONITORING-IFN
Hard contraindications
CI-PSYCH-DECOMPENSATED-FOR-INTERFERON
Reason
Alternative track presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks
IDNamePriorityCategoryWhere to orderNeeded for
TEST-CBCComplete Blood Count with DifferentialCriticallab—all tracks
TEST-CECT-CAPCECT chest/abdomen/pelvisCriticalimaging—all tracks
TEST-CMPComprehensive Metabolic PanelCriticallab—all tracks
TEST-FLOW-CYTOMETRYFlow CytometryCriticalhistologyCSD Lab ✓ (code TBC)all tracks
TEST-HBV-SEROLOGYHepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs)Criticallab—all tracks
TEST-HCV-ANTIBODYHCV AntibodyCriticallab—all tracks
TEST-HIV-SEROLOGYHIV Antibody/AntigenCriticallab—all tracks
TEST-LDHLactate DehydrogenaseCriticallab—all tracks
TEST-LFTLiver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin)Criticallab—all tracks
TEST-LN-EXCISIONAL-BIOPSYExcisional LN BiopsyCriticalhistology—aggressive
TEST-PREGNANCYBeta-HCGCriticallab—all tracks
TEST-ECHOEchocardiographyStandardimaging—aggressive
TEST-HTLV1-SEROLOGYHTLV-1/2 antibody screen + confirmatoryStandardlab—all tracks
TEST-PET-CTFDG PET/CT (whole body)Standardimaging—all tracks
TEST-NGS-LYMPHOID-PANELLymphoid NGS PanelDesiredgenomicCSD Lab ✓ (code TBC)desired (aggressive)

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track
  • Shimoyama acute or lymphoma subtype (LDH >2×ULN, BUN >ULN, albumin <ULN — any one) — aggressive variant; AZT+IFN-α inadequate, requires intensive chemo (mLSG-15) ± alloSCT.RF-ATLL-HIGH-RISK-BIOLOGY
  • Hypercalcemia (Ca >12 mg/dL) at diagnosis — hallmark of aggressive ATLL; requires bisphosphonate/calcitonin urgently and predicts aggressive subtype regardless of WBC.RF-ATLL-ORGAN-DYSFUNCTION

CONTRA-AGGRESSIVE

Hard contraindications to escalation
  • 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-ATLL-1L-AGGRESSIVE)
  • Do not give AZT+IFN for acute — wasted time, progression.
  • Do not skip mogamulizumab if available — overall survival benefit.
  • Do not give mogamulizumab before planned allo-SCT — pre-existing GVHD risk increased.
  • Do not neglect hypercalcemia treatment — bisphosphonates + hydration mandatory.
  • Do not give vincristine intrathecally — fatal.
  • Do not give full-dose anthracycline if LVEF <50%.
Standard plan (IND-ATLL-1L-INDOLENT-AZT-IFN)
  • Do not give AZT+IFN for acute / lymphoma type — poor response, delays chemo cycle.
  • Do not skip depression screening before IFN — IFN-induced depression is fatal (suicide risk).
  • Do not neglect hypercalcemia treatment — bisphosphonates + hydration.
  • Do not give IFN during pregnancy — teratogenic.
  • Do not skip TSH monitoring — IFN may induce thyroiditis.

Monitoring schedule

Monitoring schedule by treatment phase

Aggressive plan · MON-R-CHOP-REGIMEN

PhaseWindowTestsCheckpoints
baselineWithin 2 weeks before cycle 1TEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH, TEST-B2-MICROGLOBULIN, TEST-HBV-SEROLOGY, TEST-HCV-ANTIBODY, TEST-HIV-SEROLOGY, TEST-PET-CT, TEST-LN-EXCISIONAL-BIOPSY, TEST-FLOW-CYTOMETRY, TEST-CD20-IHC, TEST-ECHO, TEST-PREGNANCY, TEST-BM-ASPIRATE, TEST-BM-TREPHINE
  • Confirm CD20+ DLBCL histology; rule out double-hit (FISH for MYC/BCL2/BCL6)
  • Confirm HBV status + entecavir prophylaxis plan if HBsAg+ or anti-HBc+
  • Baseline LVEF ≥50% before doxorubicin
  • IPI calculation documented (age, ECOG, LDH, stage, extranodal sites)
  • CNS-IPI calculation if anatomic risk sites or composite score concerning
  • Fertility preservation discussion (sperm banking / oocyte cryo) for childbearing-age
on_treatmentDay 1 of every 21-day cycleTEST-CBC, TEST-CMP, TEST-LFT
  • ANC ≥1500 + platelets ≥100K before each cycle (delay or G-CSF if not)
  • Neuropathy grade documented (CTCAE) — vincristine modification if ≥2
  • LVEF re-check after cumulative doxorubicin ~300 mg/m²
interim_response_assessmentAfter cycles 2-4 (interim PET-CT)TEST-PET-CT, TEST-LDH
  • Lugano response criteria + Deauville score
  • If Deauville 4-5 with mass progression → consider salvage or trial
end_of_treatmentAfter cycle 6 (within 6-8 weeks)TEST-PET-CT, TEST-CBC, TEST-CMP, TEST-LDH
  • Confirm CR vs PR vs SD vs PD by Lugano/Deauville
  • Begin survivorship plan: cardiac surveillance schedule, vaccination catch-up, second-cancer screening
follow_up_shortEvery 3 months × 2 years post-treatmentTEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH
  • Surveillance for relapse (~40% relapse risk by 2 years overall)
  • HBV reactivation monitoring continues for 12 months post anti-CD20
follow_up_longEvery 6 months years 3-5, then annuallyTEST-CBC, TEST-LFT, TEST-ECHO
  • Late cardiomyopathy screening (LVEF) annually if cumulative dox >300
  • Annual second-malignancy screening (skin, breast, etc. age-appropriate)

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Baseline
Within 2 weeks before cycle 1
Induction · CHOEP (cyclophosphamide + doxo
21-day cycles × 6 (consider autoSCT consolidation in fit younger)
Response assessment
After cycles 2-4 (interim PET-CT)
Follow-up
Every 3 months × 2 years post-treatment

MDT brief

Skills (required) — mandatory virtual specialists (1)

  • Hematologist / oncohematologist required
    Lymphoma diagnosis — leading specialty for treatment management.
    Owns: OQ-LDH-CURRENT
    skill: hematologistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Skills (recommended) — for consideration (2)

  • Clinical pharmacist recommended
    Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
    skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
  • Pathologist (general) recommended
    Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
    Owns: OQ-CD20-CONFIRMATION
    skill: pathologistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open 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

Data quality

  • Missing critical: cd20_ihc_status, lugano_stage
  • Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
  • Unevaluated RedFlags: RF-ATLL-HIGH-RISK-BIOLOGY, RF-ATLL-HYPERCALCEMIA, RF-ATLL-INFECTION-SCREENING, RF-ATLL-ORGAN-DYSFUNCTION, RF-ATLL-TRANSFORMATION-PROGRESSION

Skill catalog (3/16 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)

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).
OptionUA registrationNSZUCost orientationAccess pathway
Aggressive plan
CHOEP (cyclophosphamide + doxorubicin + vincristine + etoposide + prednisone), 6 cycles (REG-CHOEP)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary
Standard plan
AZT (zidovudine) + IFN-α — continuous, dose-adjusted (REG-AZT-IFN-A)
✓ registered✓ covered₴-? — verify pathwayNSZU formulary

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

plan_id: PLAN-BMA-JAK3_ATLL-V1 | version: 1 | generated: 2026-05-04T14:13:16.606958+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.