OpenOnco · Treatment Plan

Treatment plan — Chronic Myeloid Leukemia

PLAN-VAR-CML-RELAPSED-V1 · v1 · 2026-06-27

Patient

VAR-CML-RELAPSED · 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-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: 2026-06-27.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT04195633	Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment of Hematological Malignancies	PHASE2	RECRUITING	Fred Hutchinson Cancer Center	—	Single country
NCT03128034	211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, or Mixed-Phenotype Acute Leukemia	PHASE1 / PHASE2	RECRUITING	Fred Hutchinson Cancer Center	—	Single country
NCT06523556	Axatilimab With or Without Azacitidine for the Treatment of Patients With Advanced Phase Myeloproliferative Neoplasms, Myeloproliferative Neoplasm/Myelodysplastic Syndrome Overlap or High Risk Chronic Myelomonocytic Leukemia	PHASE1 / PHASE2	RECRUITING	Uma Borate	—	Surrogate endpoint only Single country
NCT07033598	Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia	PHASE2	RECRUITING	Theradex	—	Single country
NCT07020533	A Vaccine (CMV-MVA Triplex Vaccine) for the Enhancement of CMV-Specific Immunity and the Prevention of CMV Viremia in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplant	PHASE1	RECRUITING	City of Hope Medical Center	—	Phase 1 only Small N (<50) Single country
NCT06297161	A Study to Learn About the Study Medicine Bosulif in Adult Patients With Chronic Myeloid Leukemia(CML).	N/A	RECRUITING	Pfizer	—	Single country
NCT06401603	A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia	PHASE1	RECRUITING	M.D. Anderson Cancer Center	—	Phase 1 only Small N (<50) Single country
NCT06368414	A Study of Treatment-free Remission in Chronic Phase Chronic Myeloid Leukemia	PHASE2	RECRUITING	Korean Society of Hematology	—	Single country
NCT07091019	A Real-world Chronic Myelogenous Leukemia (CML) Patient Disease Registry to Describe Patient Experience and Clinical Outcomes Among Patients With CML Receiving Approved First or Second Line Tyrosine Kinase Inhibitor (TKI) Therapy	N/A	RECRUITING	Novartis Pharmaceuticals	—	Single country
NCT04769947	Italian Treatment Free Remission Registry	N/A	RECRUITING	University of Turin, Italy	—	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 · 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 · NCT03128034 211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, or Mixed-Phenotype Acute Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06523556 Axatilimab With or Without Azacitidine for the Treatment of Patients With Advanced Phase Myeloproliferative Neoplasms, Myeloproliferative Neoplasm/Myelodysplastic Syndrome Overlap or High Risk Chronic Myelomonocytic Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07033598 Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07020533 A Vaccine (CMV-MVA Triplex Vaccine) for the Enhancement of CMV-Specific Immunity and the Prevention of CMV Viremia in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplant No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06297161 A Study to Learn About the Study Medicine Bosulif in Adult Patients With Chronic Myeloid Leukemia(CML). No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06401603 A Phase I Study of Decitabine, Lisaftoclax, and Olverembatinib in Patients With Advanced Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Myeloid Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06368414 A Study of Treatment-free Remission in Chronic Phase Chronic Myeloid Leukemia No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07091019 A Real-world Chronic Myelogenous Leukemia (CML) Patient Disease Registry to Describe Patient Experience and Clinical Outcomes Among Patients With CML Receiving Approved First or Second Line Tyrosine Kinase Inhibitor (TKI) Therapy 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

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-06-27.

plan_id: PLAN-VAR-CML-RELAPSED-V1 | version: 1 | generated: 2026-06-27T09:41:01.325588+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.