Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
VERIFIED-CML-L1-CML_1L_2GEN_TKI · Algorithm: ALGO-CML-1L
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-1L-2GEN-TKI
- Regimen
- 2nd-generation TKI (dasatinib OR nilotinib OR bosutinib by comorbidity matrix) — CML chronic phase 1L for high-risk / younger seeking TFR
- Drugs + NSZU
- Dasatinib (DRUG-DASATINIB) 100 mg PO once daily — DEFAULT for low-CV-risk; AVOID if pulmonary disease · continuous; lifelong unless TFR achieved · PO ✓ NSZU covered
- Nilotinib (DRUG-NILOTINIB) 300 mg PO BID on empty stomach (≥1 h before / ≥2 h after meals) — DEFAULT for low-CV-risk + no pancreatitis history; AVOID if CV disease, DM, hyperlipidemia · continuous · PO ✓ NSZU covered
- Bosutinib (DRUG-BOSUTINIB) 400 mg PO once daily with food — for patients with CV comorbidity precluding nilotinib AND pulmonary precluding dasatinib · continuous · PO ✓ NSZU covered
- Reason
- Primary current-line option selected by ALGO-CML-1L at step 3; branch-driving red flag: RF-CML-HIGH-RISK-ELTS.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-CML-1L-IMATINIB
- Regimen
- Imatinib (CML chronic phase 1L)
- Drugs + NSZU
- Imatinib (DRUG-IMATINIB) 400 mg PO once daily with food + large glass of water · continuous, lifelong (or until durable deep molecular response permits TFR attempt per ELN 2020 criteria) · PO ✓ NSZU covered
- 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 3 → branch IND-CML-1L-2GEN-TKI
- RF-SOKAL-HIGH: CML chronic phase with Sokal high risk — supports 2nd-generation TKI 1L (dasatinib / nilotinib / bosutinib) over imatinib for faster MMR/MR4.5 and improved long-term cumulative incidence of progression SRC-NCCN-MPN-2025SRC-ELN-CML-2020SRC-ESMO-CML-2017
- RF-CML-HIGH-RISK-ELTS ★ winner: CML high-risk by ELTS (EUTOS Long-Term Survival score) — favors 2nd-generation TKI (nilotinib / dasatinib / bosutinib) over imatinib for faster deep molecular response and improved long-term outcomes 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-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-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-ECHO | Echocardiography | Standard | imaging | — | aggressive |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- CML high-risk by ELTS (EUTOS Long-Term Survival score) — favors 2nd-generation TKI (nilotinib / dasatinib / bosutinib) over imatinib for faster deep molecular response and improved long-term outcomes
ELN 2020 prefers ELTS over Sokal for predicting CML-related death and guiding 1L TKI selection in younger patients seeking treatment-free remission. High-risk patients gain more from 2nd-gen TKIs in early deep molecular response, but no…
RF-CML-HIGH-RISK-ELTSSRC-NCCN-MPN-2025SRC-ELN-CML-2020SRC-ESMO-CML-2017 - 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 - CML chronic phase with Hasford (EURO) high risk — supports 2nd-generation TKI 1L (dasatinib / nilotinib / bosutinib) over imatinib; comparable rationale to Sokal-high
Hasford / EURO score (Hasford 1998) refined Sokal by adding eosinophils and basophils; high-risk = >1480. Hasford-high and Sokal-high overlap substantially but identify slightly different subsets. ELN 2020 recognizes both alongside the…
RF-HASFORD-HIGHSRC-NCCN-MPN-2025SRC-ELN-CML-2020SRC-ESMO-CML-2017 - CML chronic phase with Sokal high risk — supports 2nd-generation TKI 1L (dasatinib / nilotinib / bosutinib) over imatinib for faster MMR/MR4.5 and improved long-term cumulative incidence of progression
Sokal score (Sokal 1984) uses age, spleen size, platelet count, blast %. High-risk (Sokal >1.2) marks ~20-25% of CML-CP at diagnosis with worse 10-yr OS and PFS on imatinib vs intermediate/low. ENESTnd (Saglio 2010) and DASISION…
RF-SOKAL-HIGHSRC-NCCN-MPN-2025SRC-ELN-CML-2020SRC-ESMO-CML-2017
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-CML-1L-2GEN-TKI)
- Do not prescribe nilotinib without baseline CV evaluation + ECG + lipid panel + glucose — boxed QT warning + cumulative vascular toxicity.
- Do not prescribe dasatinib to patients with pulmonary comorbidity / prior pleural effusion — risk of severe effusion.
- Do not prescribe bosutinib to patients with IBD / severe diarrhea history — diarrhea ~70% risk.
- Do not skip pre-TKI HBV screening.
- Do not skip the fertility discussion; TKI safety during pregnancy is limited.
- Do not start without food for bosutinib (with food); STRICTLY on empty stomach for nilotinib (≥1h before / ≥2h after).
Standard plan (IND-CML-1L-IMATINIB)
- Do not skip baseline BCR-ABL1 quantitative PCR — this is baseline for milestone monitoring.
- Do not skip pre-TKI HBV screening — HBV reactivation on TKI has been described in cases.
- Do not skip the fertility discussion in young patients — TKI safety during pregnancy is limited; interferon-α — alternative at conception.
- Do not prescribe without food + a large glass of water — GI intolerance on empty stomach.
- Do not repeat imatinib 400 mg on failure — switch per ELN criteria (3 mo / 6 mo / 12 mo) to a 2nd-gen TKI.
- Do not start a TFR attempt without ≥3 years of TKI + sustained MR4.5 ≥2 years + qPCR monitoring q1-2mo after stopping.
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-ELN-CML-2020: European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia (2020)
- SRC-ESMO-CML-2017: Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2017)
- SRC-IRIS-OBRIEN-2003: Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia (2003)
- SRC-NCCN-MPN-2025: NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms (v.X.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: 2026-09-09.
| 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 2nd-generation TKI (dasatinib OR nilotinib OR bosutinib by comorbidity matrix) — CML chronic phase 1L for high-risk / younger seeking TFR (REG-2GEN-TKI-CML) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Imatinib (CML chronic phase 1L) (REG-IMATINIB-CML) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| 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.