OpenOnco · Treatment Plan

Treatment plan — Chronic Myeloid Leukemia

PLAN-CML-2L-PONA-001-V1 · v1 · 2026-06-11

Patient

CML-2L-PONA-001 · Algorithm: ALGO-CML-2L

DiagnosisChronic Myeloid Leukemia

MOH / ICD-10C92.1

ICD-O-39863/3; C42.1

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

Aggressive plan

★ DEFAULT

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

Primary current-line option selected by ALGO-CML-2L at step 4.

Other current-line alternatives (1 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Aggressive plan

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

Current-line alternative 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-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 with T315I gatekeeper mutation in the BCR-ABL1 kinase domain — resistant to all 1st/2nd-gen TKIs; requires ponatinib or asciminib (STAMP)RF-CML-T315I-MUTATION
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.RF-CML-TRANSFORMATION-PROGRESSION

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-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-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.

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

MDT brief

Discussion 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

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)

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-CML-COMORBIDITY-COMPLEX, RF-CML-FRAILTY-AGE, RF-CML-HIGH-RISK-ELTS, RF-CML-INFECTION-SCREENING, 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	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-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: 2026-06-11.

NCT	Title	Phase	Status	Sponsor	UA	Signals
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	Terns, Inc.	—	—
NCT05488548	Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors and Hematological Malignancies	PHASE1	RECRUITING	Epigenetix, Inc.	—	Phase 1 only Single country
NCT04239157	A Phase II, Open-Label, Study of Subcutaneous Canakinumab, an Anti-IL-1β Human Monoclonal Antibody, for Patients With Low or Int-1 Risk IPSS/IPSS-R Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia	PHASE2	RECRUITING	M.D. Anderson Cancer Center	—	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	M.D. Anderson Cancer Center	—	Single country
NCT04375631	CLAG-M or FLAG-Ida Chemotherapy and Reduced-Intensity Conditioning Donor Stem Cell Transplant for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelomonocytic Leukemia	PHASE1	RECRUITING	Fred Hutchinson Cancer Center	—	Phase 1 only Single country
NCT02727803	Personalized NK Cell Therapy in CBT	PHASE2	RECRUITING	M.D. Anderson Cancer Center	—	Surrogate endpoint only Single country
NCT04256317	A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study)	PHASE2 / PHASE3	RECRUITING	Taiho Oncology, Inc.	—	—
NCT05636514	Combined Evaluation of Epigenetic and Sensitising Therapy in AML and MDS	PHASE1	RECRUITING	Clinical Hub for Interventional Research (CHOIR)	—	Phase 1 only Small N (<50) Single country
NCT07165535	Quality of Life and Care Organization of Patients With Chronic Myeloid Leukemia in the Lombardy Hematology Network	N/A	RECRUITING	University of Milano Bicocca	—	Single country
NCT06409936	PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML	PHASE2	RECRUITING	Gruppo Italiano Malattie EMatologiche dell'Adulto	—	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 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 Allogeneic hematopoietic cell transplant for CML blast crisis OR multi-TKI failure (REG-ALLOHCT-CML-ADVANCED)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
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 · NCT05488548 Dual BET and CBP/p300 Inhibitor in Patients With Targeted Advanced Solid Tumors and Hematological Malignancies No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04239157 A Phase II, Open-Label, Study of Subcutaneous Canakinumab, an Anti-IL-1β Human Monoclonal Antibody, for Patients With Low or Int-1 Risk IPSS/IPSS-R Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia 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 · NCT04375631 CLAG-M or FLAG-Ida Chemotherapy and Reduced-Intensity Conditioning Donor Stem Cell Transplant for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelomonocytic Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT02727803 Personalized NK Cell Therapy in CBT No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04256317 A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study) No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05636514 Combined Evaluation of Epigenetic and Sensitising Therapy in AML and MDS No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07165535 Quality of Life and Care Organization of Patients With Chronic Myeloid Leukemia in the Lombardy Hematology Network No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06409936 PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML 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: 2026-06-11.

plan_id: PLAN-CML-2L-PONA-001-V1 | version: 1 | generated: 2026-06-11T11:52:06.136885+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.