OpenOnco · Treatment Plan

Treatment plan — Myelodysplastic Syndromes — Higher Risk

PLAN-MDS-HR-UNFIT-001-V1 · v1 · 2026-06-11

Patient

MDS-HR-UNFIT-001 · Algorithm: ALGO-MDS-HR-1L

DiagnosisMyelodysplastic Syndromes — Higher Risk

MOH / ICD-10D46.2

ICD-O-39989/3; C42.1

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

Standard plan

★ DEFAULT

Indication

IND-MDS-HR-1L-AZA

Regimen

Azacitidine (MDS-HR 1L)

Drugs + NSZU

Azacitidine (DRUG-AZACITIDINE) 75 mg/m²/day · SC days 1-7 of each 28-day cycle (or 5-2-2 schedule for outpatient convenience) · SC ✓ NSZU covered

Supportive care

SUP-HBV-PROPHYLAXIS

Reason

Primary current-line option selected by ALGO-MDS-HR-1L at step 2; branch-driving red flag: RF-MDS-TP53-MUTATION.

Other current-line alternatives (1 tracks)

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

Aggressive plan

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

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 2 → branch IND-MDS-HR-1L-AZA

RF-MDS-TP53-MUTATION ★ winner: 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 intent SRC-NCCN-AML-2025SRC-ESMO-MDS-2021SRC-IPSS-M-BERNARD-2022

Pre-treatment investigations

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

ID	Name	Priority	Category	Where to order	Needed for
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-PERIPHERAL-SMEAR	Peripheral Blood Smear	Critical	lab	CSD Lab ✓ (code TBC)	all tracks
TEST-B12-FOLATE	B12 + Folate	Standard	lab	—	standard
TEST-CMV-SEROLOGY	CMV IgG/IgM	Standard	lab	—	standard
TEST-ECHO	Echocardiography	Standard	imaging	—	desired (aggressive, standard)
TEST-IRON-PANEL	Iron Panel	Standard	lab	—	standard
TEST-RETICULOCYTE	Reticulocyte Count	Standard	lab	—	standard
TEST-URIC-ACID	Serum Uric Acid	Standard	lab	—	aggressive

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

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Standard plan (IND-MDS-HR-1L-AZA)

Do not skip pre-HMA HBV screening + prophylaxis — HMA-associated HBV reactivation has been described.
Do not stop HMA before cycle 6 without overt progression — response is often late (cycles 4-6).
Do not expect CR — most patients achieve hematologic improvement without CR; this has clinical value.
Do not skip donor search in parallel with HMA for transplant-eligible — search window 3-6 months.
Do not prescribe ven+aza in MDS-HR as 1L without trial / clinical justification — only extrapolation from VIALE-A AML, without HR-MDS-specific phase 3.

Aggressive plan (IND-MDS-HR-1L-VEN-AZA)

Do not skip venetoclax 3-day ramp + TLS prophylaxis.
Do not use ven+aza in patients non-fit for alloHCT (standard aza alone is an alternative with a better toxicity profile).
Do not expect phase-3 validation — VERONA and other trials in progress; current use is off-label.
Do not skip informed consent regarding off-label use and uncertainty about OS benefit.

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Standard plan

Induction · Azacitidine (MDS-HR 1L)

28-day cycles × Continue ≥6 cycles before declaring failure (response often delayed to cycles 4-6); continue until progression / unacceptable toxicity in responders

Aggressive plan

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

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

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-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, RF-OCC-BENZENE-MALIGNANCY-PREVENTION

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-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)

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
NCT05732103	A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes	PHASE1 / PHASE2	RECRUITING	Chordia Therapeutics, Inc.	—	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
NCT06046313	Prolonged Ultra Low-dose Decitabine Plus Venetoclax for Primary Diagnosed Elderly AMLK/MDS	PHASE2	RECRUITING	First Affiliated Hospital of Zhejiang University	—	Surrogate endpoint only Single country
NCT05601726	First-in-human Study Aiming to Characterize the Safety, Tolerability, Pharmacokinetic and Preliminary Signs of Activity of ABD-3001 in Refractory or Relapsed AML and High Risk MDS Adult Patients	PHASE1 / PHASE2	RECRUITING	Advanced BioDesign	—	Small N (<50) Single country
NCT07047183	Clinical Study of Venetoclax Combined With Azacitidine as Bridging Therapy Prior to Hematopoietic Stem Cell Transplantation in Patients With Higher-Risk Myelodysplastic Syndromes	PHASE2	RECRUITING	Yehui Tan	—	Small N (<50) Single country
NCT07107126	Safety and Proof-of-Concept Study of RPT1G in Adults With Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndromes	PHASE1	RECRUITING	Remedy Plan, Inc.	—	Phase 1 only Small N (<50) Single country
NCT06146257	A Study of GLB-001 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher Risk Myelodysplastic Syndromes	PHASE1	RECRUITING	GluBio Therapeutics Inc.	—	Phase 1 only Small N (<50) Single country
NCT00801489	Fludarabine Phosphate, Cytarabine, Filgrastim-sndz, Gemtuzumab Ozogamicin, and Idarubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome	PHASE2	RECRUITING	M.D. Anderson Cancer Center	—	Single country
NCT06013423	Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases	PHASE2	RECRUITING	Fred Hutchinson Cancer Center	—	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
Standard plan Azacitidine (MDS-HR 1L) (REG-AZA-MDS-HR)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Aggressive plan Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule (REG-VEN-AZA-AML)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Trial · NCT05732103 A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes 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 · NCT06046313 Prolonged Ultra Low-dose Decitabine Plus Venetoclax for Primary Diagnosed Elderly AMLK/MDS No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05601726 First-in-human Study Aiming to Characterize the Safety, Tolerability, Pharmacokinetic and Preliminary Signs of Activity of ABD-3001 in Refractory or Relapsed AML and High Risk MDS Adult Patients No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07047183 Clinical Study of Venetoclax Combined With Azacitidine as Bridging Therapy Prior to Hematopoietic Stem Cell Transplantation in Patients With Higher-Risk Myelodysplastic Syndromes No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07107126 Safety and Proof-of-Concept Study of RPT1G in Adults With Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndromes No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06146257 A Study of GLB-001 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher Risk Myelodysplastic Syndromes No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT00801489 Fludarabine Phosphate, Cytarabine, Filgrastim-sndz, Gemtuzumab Ozogamicin, and Idarubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome No UA site listed — international referral required	— unknown	— unknown	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	— 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-MDS-HR-UNFIT-001-V1 | version: 1 | generated: 2026-06-11T11:52:06.166011+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.