Treatment plan — DIS-MDS-HR

OpenOnco · Treatment Plan

PLAN-MDS-HR-AMLPROG-001-V1 · v1 · 2026-04-27

Patient

MDS-HR-AMLPROG-001 · Algorithm: ALGO-MDS-HR-2L

Clinical significance of mutations (ESCAT / OncoKB)

Tumor-board context — the engine does not use these tiers to rank tracks

Biomarker	Variant	ESCAT	OncoKB	Clinical significance	Drugs	Sources
No clinically actionable variants matched in this profile.

Treatment options (2 tracks)

Aggressive plan

★ DEFAULT

Indication

IND-MDS-HR-1L-VEN-AZA

Regimen

Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule

Drugs + NSZU

Venetoclax (DRUG-VENETOCLAX) Cycle 1 ramp: day 1 = 100 mg, day 2 = 200 mg, day 3 = 400 mg → days 4-28 = 400 mg PO daily; subsequent cycles = 400 mg daily continuously · PO daily; reduce to ~70-100 mg if combined with strong CYP3A4 inhibitor (posaconazole) · PO ⚠ NSZU — not for this indication
Azacitidine (DRUG-AZACITIDINE) 75 mg/m²/day · SC or IV days 1-7 of each 28-day cycle · SC ✓ NSZU covered

Supportive care

SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS

Reason

Engine default per algorithm ALGO-MDS-HR-2L: {'step': 5, 'outcome': False, 'branch': {'result': 'IND-MDS-HR-1L-VEN-AZA'}, 'fired_red_flags': [], 'winner_red_flag': None}

Aggressive plan

Indication

IND-MDS-HR-ALLOHCT

Regimen

Allogeneic hematopoietic cell transplant for high-risk MDS

Drugs + NSZU

Azacitidine (DRUG-AZACITIDINE) Pre-HCT cytoreduction: azacitidine 75 mg/m² SC days 1-7 q28d × 4-6 cycles to reduce blast burden + bridge to HCT · Bridging until donor identified + transplant slot available; conditioning regimen institution-specific (myeloablative Bu/Cy or Bu/Flu for fit younger; reduced-intensity Flu/Mel or Flu/Bu for older / comorbid) · SC ✓ NSZU covered

Supportive care

SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS

Hard contraindications

CI-ACTIVE-INFECTION-FOR-ALEMTUZUMAB

Reason

Alternative track presented for HCP consideration

Pre-treatment investigations

Investigations before treatment start · critical / standard / desired · merged across tracks

ID	Name	Priority	Category	Needed for
TEST-BM-ASPIRATE	Аспірат кісткового мозку (цитологія + flow + цитогенетика + молекулярка)	Critical	histology	all tracks
TEST-BM-TREPHINE	Трепанобіопсія кісткового мозку (core-біопсія)	Critical	histology	all tracks
TEST-CBC	Загальний аналіз крові з лейкоцитарною формулою	Critical	lab	all tracks
TEST-CMP	Розширений біохімічний аналіз крові	Critical	lab	all tracks
TEST-COAG-PANEL	Коагулограма (ПТ/МНВ, АЧТЧ, фібриноген)	Critical	lab	all tracks
TEST-FISH-PANEL	FISH-панель (специфічна для нозології)	Critical	genomic	all tracks
TEST-FLOW-CYTOMETRY	Імунофенотипування методом проточної цитометрії	Critical	histology	all tracks
TEST-HBV-SEROLOGY	Серологія HBV: HBsAg, anti-HBc, anti-HBs	Critical	lab	all tracks
TEST-HCV-ANTIBODY	Антитіла до HCV	Critical	lab	all tracks
TEST-HIV-SEROLOGY	Серологія ВІЛ (антитіла HIV-1/2 + p24)	Critical	lab	all tracks
TEST-KARYOTYPE	Класична цитогенетика (каріотип)	Critical	genomic	all tracks
TEST-LDH	Лактатдегідрогеназа (ЛДГ)	Critical	lab	all tracks
TEST-LFT	Печінкові проби (АЛТ, АСТ, білірубін, ЛФ, ГГТП, альбумін)	Critical	lab	all tracks
TEST-NGS-MYELOID-PANEL	NGS-панель мієлоїдних мутацій (AML/MDS/MPN)	Critical	genomic	all tracks
TEST-PERIPHERAL-SMEAR	Мазок периферичної крові (мануальний перегляд)	Critical	lab	all tracks
TEST-PREGNANCY	β-ХГЛ (тест на вагітність)	Critical	lab	all tracks
TEST-CMV-SEROLOGY	Серологія CMV (IgG + IgM)	Standard	lab	all tracks
TEST-ECHO	Ехокардіографія (ТТЕ) з оцінкою ФВ ЛШ	Standard	imaging	all tracks
TEST-IRON-PANEL	Залізо-обмін: феритин, TSAT, ЗЗЗС, сироваткове залізо	Standard	lab	all tracks
TEST-URIC-ACID	Сечова кислота сироватки	Standard	lab	all tracks

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

MDS patient elderly or frail (age ≥80, ECOG ≥3, life expectancy <2 years, multiple comorbidities) where best supportive care or low-intensity HMA is preferred over alloHCT or intensive disease modificationRF-MDS-FRAILTY-AGE
MDS patient with organ dysfunction limiting therapy: ECOG ≥3, severe renal impairment (CrCl <30), hepatic dysfunction (bilirubin >3× ULN), or cardiac dysfunction (LVEF <40%, NYHA III-IV)RF-MDS-ORGAN-DYSFUNCTION
MDS with TP53 mutation (mono- or biallelic) — distinct WHO 5th-ed entity with poor outcomes on HMA monotherapy and reduced alloHCT benefit; consideration of intensified / experimental therapy or palliative intentRF-MDS-TP53-MUTATION
MDS progressing to AML (≥20% blasts) or accelerated MDS-IB2 with rapid progression on HMA — switch to AML algorithm or escalate to ven+aza / intensive chemo + alloHCT bridgeRF-MDS-TRANSFORMATION-PROGRESSION
MDS-HR patient transplant-eligible: age <70-75 (per local practice), HCT-CI ≤4, adequate organ function, donor available — initiate alloHCT donor search at HMA initiation, not at HMA failureRF-MDS-TRANSPLANT-ELIGIBLE

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-MDS-HR-1L-VEN-AZA)

Не пропускати venetoclax 3-day ramp + TLS-профілактику.
Не використовувати ven+aza у пацієнтів non-fit для alloHCT (стандартний aza alone альтернатива з кращим toxicity profile).
Не очікувати phase-3 валідацію — VERONA та інші trials у процесі; поточне використання — off-label.
Не пропускати informed consent щодо off-label використання та невизначеності щодо OS benefit.

Aggressive plan (IND-MDS-HR-ALLOHCT)

НЕ відкладати donor search до HMA failure — пошук триває 3-6 місяців; розпочинати концурентно з 1L HMA.
НЕ виконувати HCT при активному uncontrolled infection — лімфодеплеція + GVHD-профілактика = high mortality.
НЕ виконувати HCT без оптимального blast control (target <10%, ideally <5%) — outcomes substantially worse при active blast burden.
НЕ ігнорувати IPSS-M molecular reclassification — ~46% reclassified vs IPSS-R; може змінити HCT timing.
НЕ припиняти HMA безпосередньо перед conditioning — продовжувати через donor search до conditioning per institution.
НЕ забувати fertility preservation у молодих пацієнтів перед conditioning.
НЕ пропускати TP53-status testing — впливає на conditioning intensity, post-HCT maintenance, прогноз.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Induction · Venetoclax + Azacitidine (AML,

28-day cycles × Continue until progression / unacceptable toxicity (median ~12 cycles in VIALE-A; ~25-30% achieve durable remission)

MDT brief

Skills (recommended) — for consideration (1)

Клінічний фармацевт recommended
Хіміоімунотерапевтичний схема — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

OQ-LDH-CURRENT
Який актуальний LDH? Маркер пухлинного навантаження і трансформації.
LDH входить у прогностичні індекси індолентних лімфом.
→ hematologist

Data quality

Unevaluated RedFlags: RF-IPSS-M-HIGH, RF-IPSS-R-VERY-HIGH, RF-MDS-FRAILTY-AGE, RF-MDS-HIGH-RISK-IPSS, RF-MDS-INFECTION-SCREENING, RF-MDS-ORGAN-DYSFUNCTION, RF-MDS-TP53-MUTATION, RF-MDS-TRANSFORMATION-PROGRESSION, RF-MDS-TRANSPLANT-ELIGIBLE

Skill catalog (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
Specialist з клітинної терапії (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Клінічний фармацевт	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Гематолог / онкогематолог	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Гематопатолог (специфічно для лімфом / лейкозів / мієломи)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Інфекціоніст / гепатолог	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Медичний онколог (хіміотерапевт солідних пухлин)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Молекулярний генетик / молекулярний онколог	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Паліативна допомога	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Патолог (загальний)	`pathologist`	v0.1.0	2026-04-25	pathology
Сімейний лікар / терапевт	`primary_care`	v0.1.0	2026-04-25	primary_care
Психолог / онкопсихолог	`psychologist`	v0.1.0	2026-04-25	psychosocial
Радіотерапевт (променева терапія)	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Лікар-радіолог	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Соціальний працівник / кейс-менеджер	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Хірург-онколог	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Specialist з трансплантації (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-ESMO-MDS-2021: Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2021)
SRC-IPSS-M-BERNARD-2022: Molecular International Prognostic Scoring System for Myelodysplastic Syndromes (2022)
SRC-NCCN-AML-2025: NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia (v.X.2025)
SRC-VIALE-A-DINARDO-2020: Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia (2020)

Експериментальні опції (клінічні дослідження)

Третій трек плану — open-enrollment trials з ClinicalTrials.gov. Останнє оновлення: 2026-04-26. Render-time metadata; engine selection не змінюється цим блоком (CHARTER §8.3).

NCT	Name	Phase	Статус	Спонсор	UA
NCT06597734	A Phase 2 Study Evaluating Olutasidenib in Combination With Hypomethylating Agents in Patients With IDH1-mutated Higher-risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Advanced Myeloproliferative Neoplasm	PHASE2	RECRUITING	M.D. Anderson Cancer Center	—
NCT06612944	Prophylactic Intervention for Relapse Prevention Post-Allogeneic Transplantation in Very High-Risk MDS Patients Based on IPSS-M Stratification	PHASE2	RECRUITING	Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine	—
NCT03214562	Venetoclax With Combination Chemotherapy in Treating Patients With Newly Diagnosed or Relapsed or Refractory Acute Myeloid Leukemia	PHASE1 / PHASE2	RECRUITING	M.D. Anderson Cancer Center	—
NCT07384715	First-in-human (FIH) Trial of GEN3018 in Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) or Higher-risk Myelodysplastic Syndrome (HR-MDS)	PHASE1	RECRUITING	Genmab	—
NCT03113643	SL-401 in Combination With Azacitidine or Azacitidine/Venetoclax in Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)	PHASE1	RECRUITING	Dana-Farber Cancer Institute	—
NCT04128748	Liposomal Cytarabine and Daunorubicin (CPX-351) and Quizartinib for the Treatment of Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome	PHASE1 / PHASE2	RECRUITING	M.D. Anderson Cancer Center	—
NCT06034275	Study of VIP943 in Subjects With Advanced CD123+ Hematologic Malignancies	PHASE1	RECRUITING	Vincerx Pharma, Inc.	—
NCT03661307	Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome	PHASE1 / PHASE2	RECRUITING	M.D. Anderson Cancer Center	—
NCT06013423	Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases	PHASE2	RECRUITING	Fred Hutchinson Cancer Center	—
NCT03383575	Azacitidine and Enasidenib in Treating Patients With IDH2-Mutant Myelodysplastic Syndrome	PHASE2	RECRUITING	M.D. Anderson Cancer Center	—

Перевіряти статус набору безпосередньо у дослідницькому центрі. Дані ctgov можуть відставати від поточного статусу UA-сайтів.

Доступність опцій в Україні

Per-track UA registration · НСЗУ · cost · access pathway. Render-time metadata; engine selection не залежить від цих полів (CHARTER §8.3).

Опція	Реєстрація UA	НСЗУ	Cost orientation	Access pathway
Aggressive plan Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule (REG-VEN-AZA-AML)	✓ зареєстровано	✓ покривається	₴-? — verify pathway	НСЗУ formulary
Aggressive plan Allogeneic hematopoietic cell transplant for high-risk MDS (REG-ALLOHCT-MDS-HR)	✓ зареєстровано	✓ покривається	₴-? — verify pathway	НСЗУ formulary
Trial · NCT06597734 A Phase 2 Study Evaluating Olutasidenib in Combination With Hypomethylating Agents in Patients With IDH1-mutated Higher-risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Advanced Myeloproliferative Neoplasm No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT06612944 Prophylactic Intervention for Relapse Prevention Post-Allogeneic Transplantation in Very High-Risk MDS Patients Based on IPSS-M Stratification No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT03214562 Venetoclax With Combination Chemotherapy in Treating Patients With Newly Diagnosed or Relapsed or Refractory Acute Myeloid Leukemia No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT07384715 First-in-human (FIH) Trial of GEN3018 in Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) or Higher-risk Myelodysplastic Syndrome (HR-MDS) No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT03113643 SL-401 in Combination With Azacitidine or Azacitidine/Venetoclax in Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS) or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT04128748 Liposomal Cytarabine and Daunorubicin (CPX-351) and Quizartinib for the Treatment of Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT06034275 Study of VIP943 in Subjects With Advanced CD123+ Hematologic Malignancies No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT03661307 Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT06013423 Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor
Trial · NCT03383575 Azacitidine and Enasidenib in Treating Patients With IDH2-Mutant Myelodysplastic Syndrome No UA site listed — international referral required	— невідомо	— невідомо	self-pay: ₴0/course	Trial sponsor

Інформація про ціни — orientation. Перевіряти у конкретній аптеці / foundation / трайл-сайті. Status updated: 2026-04-27.

plan_id: PLAN-MDS-HR-AMLPROG-001-V1 | version: 1 | generated: 2026-04-27T12:36:01.364461+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.