Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
BMA-IDH1_R132H_MDS_HR · Algorithm: ALGO-MDS-HR-1L
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 |
|---|
| ESCAT: clinical review pendingBIO-IDH-MUTATION | IDH1 R132H | IIA | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal Trial or research option - SRC-CIVIC: Level C (Supports, Sensitivity/Response)
- SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| IDH1 R132 in MDS — ivosidenib monotherapy active (DiNardo et al. JCO 2021 — ORR 75% MDS, CR 38%). Ivosidenib + azacitidine combos in trial. Off-label NCCN-supported. | ivosidenib (off-label MDS)
ivosidenib + azacitidine (trial) | |
| ESCAT: clinical review pendingBIO-IDH-MUTATION | IDH2 R140Q | IIA | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal Trial or research option - SRC-CIVIC: Level C (Supports, Sensitivity/Response)
- SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| IDH2 R140Q in MDS — enasidenib monotherapy active in MDS (NCT01915498, DiNardo et al. Blood 2018). IDH-mut MDS often progresses to AML; IDH2i can delay transformation. Not yet on full FDA MDS label (off-label use NCCN-supported). | enasidenib (off-label MDS) | - SRC-ESMO-MDS-2021
- SRC-IPSS-M-BERNARD-2022
|
| ESCAT: clinical review pendingBIO-IDH-MUTATION | IDH2 R172K | IIA | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal Trial or research option - SRC-CIVIC: Level C (Supports, Sensitivity/Response)
- SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| IDH2 R172K in MDS — same enasidenib rationale as R140Q. | enasidenib (off-label MDS) | |
Primary current-line option
- 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 4.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- 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
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 modification
Triggers de-escalation: in MDS-HR, opt for HMA or best-supportive-care pathway over alloHCT (which has high TRM in this group); in MDS-LR, emphasize transfusion strategy + iron chelation + symptom management. STUB — requires clinical…
RF-MDS-FRAILTY-AGESRC-NCCN-AML-2025SRC-ESMO-MDS-2021 - 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)
Triggers de-escalation in MDS-HR (skip alloHCT track; consider lower HMA dose or supportive care only) and in MDS-LR (avoid lenalidomide if severe renal impairment; avoid ESA if uncontrolled HTN). CrCl <30 also drives lenalidomide dose…
RF-MDS-ORGAN-DYSFUNCTIONSRC-NCCN-AML-2025SRC-ESMO-MDS-2021 - 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
TP53-mutated MDS is its own WHO 5th-edition entity with median OS ~6-9 months on standard HMA. AlloHCT carries higher relapse risk vs TP53-wt. Active research questions: ven+aza vs aza alone, magrolimab + aza (failed phase-3 ENHANCE)…
RF-MDS-TP53-MUTATIONSRC-NCCN-AML-2025SRC-ESMO-MDS-2021SRC-IPSS-M-BERNARD-2022 - 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 bridge
≥20% blasts = AML by WHO 2022; switch to AML algorithm. HMA failure in MDS-HR has dismal prognosis (~6-month median OS without alloHCT); ven+aza or intensive chemo + alloHCT bridge are the rescue options. STUB — requires clinical co-lead…
RF-MDS-TRANSFORMATION-PROGRESSIONSRC-NCCN-AML-2025SRC-ESMO-MDS-2021 - 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 failure
AlloHCT is the only curative option for MDS-HR; survival benefit consistently demonstrated in IPSS-R high / very-high. Biological-age + comorbidity + donor + caregiver support determine eligibility, not chronological age alone (HCT-CI /…
RF-MDS-TRANSPLANT-ELIGIBLESRC-NCCN-AML-2025SRC-ESMO-MDS-2021
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)
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-ANKRD26-CONFIRMED-CARRIER, RF-DDX41-CONFIRMED-CARRIER, RF-ETV6-CONFIRMED-CARRIER, RF-IATROGENIC-ASCT-SECONDARY-MDS-AML-PREVENTION, 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, RF-RUNX1-CONFIRMED-CARRIER
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-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)
Last synced: 2026-08-17 · ctgov.
No active trials matched this scenario in ctgov.
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 |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-17.