Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
VERIFIED-CML-L2-CML_ADVANCED_ALLOHCT · Algorithm: ALGO-CML-2L
Etiological driver
Etiological driver · etiologically_driven archetype
Chronic Myeloid Leukemia
- BCR-ABL1 fusion arising from t(9;22)(q34;q11.2) (Philadelphia chromosome) in 100% — defining + targetable driver
- p210 (Major BCR breakpoint, e13a2 / e14a2): classic CML (>95%)
- p190 (minor BCR, e1a2): more often Ph+ ALL, occasionally lymphoid-blast-phase CML
- p230 (micro BCR, e19a2): rare, indolent neutrophilic CML
- Sporadic; rare environmental association (ionizing radiation)
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. |
Primary current-line option
- Indication
- IND-CML-ADVANCED-ALLOHCT
- Regimen
- Allogeneic hematopoietic cell transplant for CML blast crisis OR multi-TKI failure
- Drugs + NSZU
Conditioning — conditioning before allo-HCT — myeloablative (Bu/Cy or Cy/TBI) for fit younger; reduced-intensity (Flu/Mel) for older; cytarabine per institutional protocol days -7 to -1
- Cytarabine (DRUG-CYTARABINE) Conditioning regimen (variable per institution): typically myeloablative (Bu/Cy or Cy/TBI) for fit younger; reduced-intensity (Flu/Mel) for older · Pre-transplant conditioning days -7 to -1 · IV ⚠ NSZU — not for this indication
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB
- Reason
- Primary current-line option selected by ALGO-CML-2L at step 1; branch-driving red flag: RF-CML-TRANSFORMATION-PROGRESSION.
Other current-line alternatives (2 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-CML-2L-PONATINIB-T315I
- Regimen
- Ponatinib for CML T315I+ OR post ≥2 TKI failure
- Drugs + NSZU
- Ponatinib (DRUG-PONATINIB) 45 mg PO once daily; reduce to 15 mg PO daily upon achievement of MMR (≤0.1% IS) per OPTIC response-adjusted dosing · Continuous; dose-titrate based on response + vascular monitoring · PO ✗ Not registered in UA
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-CML-3L-ASCIMINIB
- Regimen
- Asciminib (STAMP) for CML-CP 3L+ post-multi-TKI failure
- Drugs + NSZU
- Asciminib (DRUG-ASCIMINIB) 40 mg PO BID OR 80 mg PO once daily (T315I-negative); 200 mg PO BID for T315I-positive · Continuous, with consistent meal timing (avoid high-fat meal); until progression / intolerance · PO ✗ Not registered in UA
- Reason
- Current-line alternative presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 1 → branch IND-CML-ADVANCED-ALLOHCT
- RF-CML-TRANSFORMATION-PROGRESSION ★ winner: CML in accelerated or blast phase: ≥10% blasts in PB or BM (accelerated), ≥20% blasts (blast phase), or extramedullary blasts. Treatment intent shifts from chronic-phase TKI to acute-leukemia-style induction + alloHCT. SRC-NCCN-MPN-2025SRC-ELN-CML-2020SRC-ESMO-CML-2017
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-NGS-MYELOID-PANEL | Myeloid NGS Panel | Critical | genomic | CSD Lab ✓ (code TBC) | all tracks |
| TEST-PREGNANCY | Beta-HCG | Critical | lab | — | all tracks |
| TEST-CMV-SEROLOGY | CMV IgG/IgM | Standard | lab | — | all tracks |
| TEST-ECHO | Echocardiography | Standard | imaging | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- CML patient with cardiovascular / metabolic / pulmonary comorbidity profile that constrains 2nd-generation TKI choice. Specifically: uncontrolled hypertension, prior arterial thrombotic event, QTc-prolongation risk (baseline QTc > 460 ms or QT-prolonging medications), pancreatitis history, pulmonary hypertension, or pleural-effusion-prone state. Drives selection toward asciminib (STAMP inhibitor, cleanest CV/QTc profile) over nilotinib (CV / QTc / metabolic risk), dasatinib (pleural effusion / pulmonary hypertension), or bosutinib (GI / hepatic) when 2nd-gen TKI is otherwise indicated by RF-CML-HIGH-RISK-ELTS.
Co-determines TKI selection with RF-CML-HIGH-RISK-ELTS. The combination matters: high-risk CML *plus* CV-comorbidity → asciminib preferred (per ASCEMBL trial 3L+ data extrapolating to comorbid 1L use under expanded ELN guidance)…
RF-CML-COMORBIDITY-COMPLEXSRC-NCCN-MPN-2025SRC-ESMO-CML-2017SRC-ELN-CML-2020 - CML patient elderly or frail (age ≥75, ECOG ≥2 with multiple comorbidities) where toxicity profile + life-expectancy considerations favor imatinib over higher-toxicity 2nd-gen TKIs
Imatinib generally preferred for elderly / frail patients given: (1) lifetime CV-event risk on nilotinib increases with age; (2) treatment-free remission less of a goal in elderly; (3) cost / generic availability + Ukraine reimbursement…
RF-CML-FRAILTY-AGESRC-NCCN-MPN-2025SRC-ELN-CML-2020 - CML patient with comorbidity excluding specific 2nd-gen TKIs: significant cardiovascular disease (PAOD, prior MI/stroke, uncontrolled HTN — avoid nilotinib/ponatinib), pulmonary disease (COPD, prior pleural disease — avoid dasatinib), severe GI disease (avoid bosutinib), pancreatitis history (avoid nilotinib)
Direction "investigate" — surfaces comorbidity-matched TKI choice as a supplementary annotation rather than a binary indication switch. ELN 2020 comorbidity matrix: - CV disease / hyperlipidemia / DM → AVOID nilotinib + ponatinib…
RF-CML-ORGAN-DYSFUNCTIONSRC-NCCN-MPN-2025SRC-ELN-CML-2020 - CML with T315I gatekeeper mutation in the BCR-ABL1 kinase domain — resistant to all 1st/2nd-gen TKIs; requires ponatinib or asciminib (STAMP)
T315I emergence on imatinib / 2nd-gen TKI mandates switch to ponatinib (full-dose 45 mg → response-adjusted to 15 mg per OPTIC) or asciminib STAMP (response rates ~50% in T315I-positive). Both NOT registered in Ukraine — major access…
RF-CML-T315I-MUTATIONSRC-NCCN-MPN-2025SRC-ELN-CML-2020 - CML in accelerated or blast phase: ≥10% blasts in PB or BM (accelerated), ≥20% blasts (blast phase), or extramedullary blasts. Treatment intent shifts from chronic-phase TKI to acute-leukemia-style induction + alloHCT.
Triggers HOLD on chronic-phase 1L algorithm. Accelerated/blast-phase CML is a clinical emergency: high-dose 2nd/3rd-gen TKI (dasatinib 140 mg or ponatinib if T315I), urgent donor search for alloHCT, induction chemotherapy (myeloid blast…
RF-CML-TRANSFORMATION-PROGRESSIONSRC-NCCN-MPN-2025SRC-ELN-CML-2020SRC-ESMO-CML-2017
CONTRA-AGGRESSIVE
Hard contraindications to escalation
- 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-CML-ADVANCED-ALLOHCT)
- Do NOT continue TKI-only therapy in blast crisis — alloHCT pathway is considered in the first weeks after transformation.
- Do NOT perform HCT during active uncontrolled infection — lymphodepletion + GVHD prophylaxis = high mortality.
- Do NOT perform HCT without optimal disease control — outcomes substantially worse with active blast crisis.
- Do NOT ignore donor-search timing — international donor may require 2-3 months; start search early.
- Do NOT discontinue TKI immediately before conditioning in blast crisis — continue through conditioning per institution.
- Do NOT skip post-HCT TKI maintenance (≥2 years) — reduces relapse rate.
- Do NOT forget fertility preservation in young patients before conditioning — myeloablative regimen is usually sterilizing.
Aggressive plan (IND-CML-2L-PONATINIB-T315I)
- Do NOT prescribe without baseline cardiovascular workup (ECG, BP, lipid panel, fasting glucose, ABI if PAD risk).
- Do NOT ignore aggressive CV risk-factor management — cumulative vascular toxicity is not reversible.
- Do NOT maintain full-dose 45 mg after achieving MMR — switch to 15 mg per OPTIC; reduces vascular events ~50%.
- Do NOT prescribe in recent MI / stroke / severe PAD — absolute CI.
- Do NOT combine with strong CYP3A4 inhibitor without dose reduction.
- Do NOT continue after a new arterial occlusive event — permanently discontinue, switch to asciminib (T315I high-dose) or alloHCT.
- Do NOT confirm the plan without funding pathway — drug not registered in Ukraine.
Aggressive plan (IND-CML-3L-ASCIMINIB)
- Do NOT prescribe without kinase-domain mutation testing at the time of failure — T315I requires a different dose (200 mg BID); other mutations have a different resistance pattern.
- Do NOT ignore meals — high-fat meal reduces bioavailability; maintain consistent timing.
- Do NOT combine with strong CYP3A4 inhibitors without dose reduction.
- Do NOT ignore baseline + regular lipase + glucose — subclinical pancreatitis + hyperglycemia documented.
- Do NOT discontinue for transient cytopenia — most common reason for dose hold; recovery typically rapid with G-CSF.
- Do NOT confirm the plan without funding pathway — drug not registered in Ukraine.
- Do NOT forget alloHCT as a curative alternative for fit-young patients — asciminib is not curative.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · Ponatinib for CML T315I+ OR post ≥2 TKI failure
28-day cycles × Continuous until progression / unacceptable toxicity / proceed to alloHCT
Aggressive plan
Induction · Asciminib (STAMP) for CML-CP 3L+ post-multi-TKI failure
28-day cycles × Continuous until progression / unacceptable toxicity
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (2 steps)
| # | Owner | Topic | Action |
|---|
| 1 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 2 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
Skills (recommended) — for consideration (1)
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-CML-COMORBIDITY-COMPLEX, RF-CML-FRAILTY-AGE, RF-CML-HIGH-RISK-ELTS, RF-CML-ORGAN-DYSFUNCTION, RF-CML-T315I-MUTATION, RF-CML-TRANSFORMATION-PROGRESSION, RF-HASFORD-HIGH, RF-SOKAL-HIGH
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).
| 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-ASCEMBL-REA-2021: Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure (2021)
- SRC-ELN-CML-2020: European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia (2020)
- SRC-NCCN-MPN-2025: NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms (v.X.2025)
- SRC-PACE-CORTES-2013: A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias (2013)
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: 2026-09-09.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT06787144 | ELVN-001 for the Treatment of Chronic Myeloid Leukemia With and Without T315I Mutation in Japanese Participants | PHASE1 | RECRUITING | — | Phase 1 only Small N (<50) Single country | |
| NCT06163430 | A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (CARDINAL) | PHASE1 / PHASE2 | RECRUITING | — | — | |
| NCT06712810 | Q702 for the Treatment of Patients With Hematologic Malignancies | PHASE1 | RECRUITING | — | Phase 1 only Small N (<50) Surrogate endpoint only Single country | |
| NCT03896269 | CPX-351 in Treating Patients With Relapsed or Refractory High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia | PHASE1 | RECRUITING | — | Phase 1 only Small N (<50) Surrogate endpoint only Single country | |
| NCT04877522 | Asciminib Roll-over Study | PHASE4 | RECRUITING | — | — | |
| NCT04769947 | Italian Treatment Free Remission Registry | N/A | RECRUITING | — | Single country | |
| NCT05807932 | Venetoclax in Addition to Sequential Conditioning With Fludarabine / Amsacrine / Ara-C (FLAMSA) + Treosulfan for Allogeneic Blood Stem Cell Transplantation in Patients With MDS, CMML or sAML | PHASE1 / PHASE2 | RECRUITING | — | Small N (<50) Single country | |
| NCT01137825 | Registry of Older Patients With Cancer | N/A | RECRUITING | — | Single country | |
| NCT02115295 | Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia | PHASE2 | RECRUITING | — | Single country | |
| NCT02333604 | Cancer Experience Registry (CER) for Cancer Patients and Caregivers | N/A | RECRUITING | — | 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).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Aggressive plan Allogeneic hematopoietic cell transplant for CML blast crisis OR multi-TKI failure (REG-ALLOHCT-CML-ADVANCED) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Ponatinib for CML T315I+ OR post ≥2 TKI failure (REG-PONATINIB-CML) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Asciminib (STAMP) for CML-CP 3L+ post-multi-TKI failure (REG-ASCIMINIB-CML) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Trial · NCT06787144 ELVN-001 for the Treatment of Chronic Myeloid Leukemia With and Without T315I Mutation in Japanese Participants No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06163430 A Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TERN-701 in Participants With Chronic Myeloid Leukemia (CARDINAL) No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06712810 Q702 for the Treatment of Patients With Hematologic Malignancies No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT03896269 CPX-351 in Treating Patients With Relapsed or Refractory High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04877522 Asciminib Roll-over Study No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT04769947 Italian Treatment Free Remission Registry No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05807932 Venetoclax in Addition to Sequential Conditioning With Fludarabine / Amsacrine / Ara-C (FLAMSA) + Treosulfan for Allogeneic Blood Stem Cell Transplantation in Patients With MDS, CMML or sAML No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT01137825 Registry of Older Patients With Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT02115295 Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT02333604 Cancer Experience Registry (CER) for Cancer Patients and Caregivers 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: 2026-09-09.