Patient
PMF-POST-RUX-HCT-001 · Algorithm: ALGO-PMF-2L
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 |
|---|
| BIO-JAK2 | V617F (exon 14 — present in ~50-60% of primary myelofibrosis) | IA | Molecular evidence option Trial or research option - SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| JAK2 V617F is one of three defining drivers in primary myelofibrosis (~50-60%; CALR ~25%, MPL ~5-10%, triple-negative ~10%) and a WHO 2022 / ICC 2022 major diagnostic criterion (per SRC-NCCN-MPN-2025, SRC-ESMO-MPN-2015). Treatment by symptom burden / risk score (DIPSS- Plus, MIPSS70, MIPSS70+v2): symptomatic intermediate/high-risk → ruxolitinib (COMFORT-I Verstovsek 2012 — 41.9% spleen response vs 0.7% placebo, OS benefit on extended follow-up); fedratinib for ruxolitinib-failure (JAKARTA2 Harrison 2017 — 31% spleen response in RUX-failure); momelotinib for anemic patients (MOMENTUM Verstovsek 2023 — superior anemia + symptom benefit vs danazol). Allogeneic HCT is the only curative therapy and is recommended for transplant- eligible higher-risk patients per SRC-NCCN-MPN-2025. | ruxolitinib monotherapy (intermediate-2 / high-risk per SRC-COMFORT-I-VERSTOVSEK-2012, SRC-NCCN-MPN-2025)
fedratinib monotherapy (post-ruxolitinib failure per SRC-JAKARTA2-HARRISON-2017)
momelotinib monotherapy (MF + anemia per SRC-MOMENTUM-VERSTOVSEK-2023)
allogeneic HCT (transplant-eligible higher-risk per SRC-NCCN-MPN-2025, SRC-DIPSS-PLUS-GANGAT-2011) | - SRC-NCCN-MPN-2025
- SRC-ESMO-MPN-2015
- SRC-COMFORT-I-VERSTOVSEK-2012
- SRC-JAKARTA2-HARRISON-2017
- SRC-MOMENTUM-VERSTOVSEK-2023
- SRC-DIPSS-PLUS-GANGAT-2011
|
Primary current-line option
- Indication
- IND-PMF-MOMELOTINIB-ANEMIA
- Regimen
- Momelotinib (Ojjaara) for MF with anemia
- Drugs + NSZU
- Momelotinib (DRUG-MOMELOTINIB) 200 mg PO once daily (with or without food) · Continuous; cycles of 28 days; until progression / unacceptable toxicity · PO ✗ Not registered in UA
- Supportive care
- SUP-HBV-PROPHYLAXIS
- Reason
- Primary current-line option selected by ALGO-PMF-2L at step 3; branch-driving red flag: RF-PMF-ANEMIA-DOMINANT.
Other current-line alternatives (2 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-PMF-2L-FEDRATINIB
- Regimen
- Fedratinib (Inrebic) for ruxolitinib-resistant / intolerant PMF
- Drugs + NSZU
- Fedratinib (DRUG-FEDRATINIB) 400 mg PO once daily with food · Continuous; cycles of 28 days; until progression / unacceptable toxicity · PO ⚠ Out-of-pocket
- Supportive care
- SUP-HBV-PROPHYLAXIS
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-PMF-ALLOHCT-HIGH-RISK
- Regimen
- Allogeneic hematopoietic cell transplant for high-risk PMF
- Drugs + NSZU
Bridging to main therapy — JAKi bridging 3-6 months pre-HCT — ruxolitinib optimization to reduce spleen volume + symptom burden; taper 5-7 days before conditioning
- Ruxolitinib (DRUG-RUXOLITINIB) JAKi optimization 3-6 months pre-HCT (5-20 mg PO BID by baseline plt) to reduce spleen volume + symptom burden; taper 5-7 days before conditioning · Pre-HCT bridging; conditioning regimen institution-specific (myeloablative Bu/Flu or Bu/Cy for fit younger; reduced-intensity Flu/Mel or Flu/Bu for older / comorbid) · PO ✓ NSZU covered
- 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
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 3 → branch IND-PMF-MOMELOTINIB-ANEMIA
- RF-PMF-ANEMIA-DOMINANT ★ winner: PMF with anemia as dominant clinical problem (Hb <10 g/dL OR transfusion-dependent) — momelotinib preferred over ruxolitinib (MOMENTUM trial: spleen + symptom + Hb improvement) SRC-NCCN-MPN-2025SRC-COMFORT-I-VERSTOVSEK-2012
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-PERIPHERAL-SMEAR | Peripheral Blood Smear | Critical | lab | 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 |
| TEST-IRON-PANEL | Iron Panel | Standard | lab | — | all tracks |
| TEST-RETICULOCYTE | Reticulocyte Count | Standard | lab | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- PMF with anemia as dominant clinical problem (Hb <10 g/dL OR transfusion-dependent) — momelotinib preferred over ruxolitinib (MOMENTUM trial: spleen + symptom + Hb improvement)
Direction "investigate" — surfaces JAKi-selection annotation. Momelotinib's ACVR1 inhibition lowers hepcidin → improves anemia vs ruxolitinib (which often worsens anemia). NOT registered in Ukraine — major access barrier. Alternative…
RF-PMF-ANEMIA-DOMINANTSRC-NCCN-MPN-2025SRC-COMFORT-I-VERSTOVSEK-2012 - PMF progressing toward AML (blasts in PB ≥10% accelerated, ≥20% blast-phase / post-MPN AML), rapid splenic enlargement, or rising LDH — re-stage with BM, accelerate alloHCT, consider AML-style therapy if blast-phase
Post-MPN AML has dismal prognosis (~5-month median OS); ven+aza achieves modest response. Most patients with ≥10% PB blasts and fit-enough biology should be on accelerated alloHCT trajectory. STUB — requires clinical co-lead signoff.
RF-PMF-BLAST-PROGRESSIONSRC-NCCN-MPN-2025SRC-DIPSS-PLUS-GANGAT-2011 - PMF patient elderly or frail (age ≥75, ECOG ≥3, or HCT-CI ≥4) — alloHCT off the table; symptom-directed therapy (ruxolitinib for splenomegaly + symptoms, momelotinib for anemia, transfusion + supportive care)
AlloHCT TRM in elderly PMF >40-50% — almost always off the table. Symptom-directed JAKi as the dominant track. STUB — requires clinical co-lead signoff.
RF-PMF-FRAILTY-AGESRC-NCCN-MPN-2025SRC-DIPSS-PLUS-GANGAT-2011 - PMF intermediate-2 or high risk by DIPSS-Plus — alloHCT referral mandatory in eligible patients (only curative option); ruxolitinib for symptomatic splenomegaly + symptoms while awaiting transplant
DIPSS-Plus int-2 / high → median OS ~2.9 / 1.3 years without alloHCT. AlloHCT in fit patients improves OS but carries 30-50% TRM. Ruxolitinib bridges symptoms + spleen; does NOT eliminate clone but may extend OS in pooled COMFORT…
RF-PMF-HIGH-RISK-DIPSSSRC-NCCN-MPN-2025SRC-DIPSS-PLUS-GANGAT-2011SRC-ESMO-MPN-2015 - PMF patient with organ dysfunction limiting JAK-inhibitor or alloHCT eligibility: severe thrombocytopenia (plt <50K — affects ruxolitinib dose; pacritinib option), severe hepatic dysfunction, or significant cardiac/pulmonary comorbidity
Direction "investigate" — surfaces JAKi-selection / dose-attenuation annotation. Severe thrombocytopenia: ruxolitinib 5 mg BID (or pacritinib 200 mg BID, no dose adjust for plt). Hepatic dysfunction: avoid ruxolitinib (CYP3A4). AlloHCT…
RF-PMF-ORGAN-DYSFUNCTIONSRC-NCCN-MPN-2025SRC-COMFORT-I-VERSTOVSEK-2012
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-PMF-MOMELOTINIB-ANEMIA)
- Do NOT prescribe without HBV / HCV / HIV / TB screening — JAKi reactivation risk.
- Do NOT combine with ruxolitinib — choose one JAKi.
- Do NOT ignore baseline + serial LFT — hepatotoxicity in MOMENTUM.
- Do NOT continue without response — assessment at 24 weeks; switch if no symptom + anemia improvement.
- Do NOT forget alloHCT-pathway for transplant-eligible — momelotinib is not curative.
- Do NOT combine with OATP1B1/1B3 substrates (rosuvastatin) without caution.
- Do NOT confirm plan without funding pathway — drug not registered in Ukraine.
Aggressive plan (IND-PMF-2L-FEDRATINIB)
- Do NOT initiate without baseline thiamine measurement + correction of deficiency — boxed warning, fatal cases documented.
- Do NOT skip prophylactic thiamine 100 mg PO daily throughout therapy.
- Do NOT ignore GI symptoms — take with food + active loperamide management; severe diarrhea causes dehydration.
- Do NOT combine with strong CYP3A4-inhibitor without dose reduction to 200 mg.
- Do NOT continue with Wernicke symptoms (confusion, ataxia, ophthalmoplegia) — discontinue + IV thiamine.
- Do NOT forget alloHCT-pathway for transplant-eligible — fedratinib is not curative.
- Do NOT confirm plan without funding pathway — drug not registered in Ukraine.
Aggressive plan (IND-PMF-ALLOHCT-HIGH-RISK)
- Do NOT delay alloHCT discussion until JAKi failure — JAKi does not cure MF, donor search takes 3-6 months.
- Do NOT perform HCT with active uncontrolled infection — lymphodepletion + GVHD prophylaxis = high mortality.
- Do NOT perform splenectomy before HCT routinely — high peri-op mortality in MF; only for refractory massive splenomegaly per institutional expertise.
- Do NOT abrupt-stop ruxolitinib before conditioning — taper 5-7 days; cytokine rebound life-threatening.
- Do NOT ignore MIPSS70+ molecular reclassification — HMR mutations increase risk; may change HCT timing.
- Do NOT forget fertility preservation in young patients before conditioning.
- Do NOT forget donor-search timing — international donor may take 2-3 months.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · Momelotinib (Ojjaara) for MF with anemia
28-day cycles × Continuous until progression / unacceptable toxicity
Aggressive plan
Induction · Fedratinib (Inrebic) for ruxolitinib-resistant / intolerant PMF
28-day cycles × Continuous until progression / unacceptable toxicity
MDT brief
Discussion questions (1, 0 blocking)
MDT talk tree (3 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. |
| 3 | social_worker_case_manager | Specialist review | Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed. |
Skills (recommended) — for consideration (2)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Social worker / case manager recommended
Plan includes drugs without NSZU reimbursement — patient access pathway must be assessed.
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-DIPSS-PLUS-HIGH, RF-PMF-BLAST-PROGRESSION, RF-PMF-FRAILTY-AGE, RF-PMF-HIGH-RISK-DIPSS, RF-PMF-INFECTION-SCREENING, RF-PMF-ORGAN-DYSFUNCTION
Technical MDT skill metadata (2/16 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-DIPSS-PLUS-GANGAT-2011: DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status (2011)
- SRC-ESMO-MPN-2015: Philadelphia-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2015)
- SRC-JAKARTA2-HARRISON-2017: Janus kinase inhibition with fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2) (2017)
- SRC-MOMENTUM-VERSTOVSEK-2023: Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study (2023)
- SRC-NCCN-MPN-2025: NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms (v.X.2025)
Experimental options (clinical trials)
Last synced: 2026-07-26 · 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 |
|---|
| Aggressive plan Momelotinib (Ojjaara) for MF with anemia (REG-MOMELOTINIB-PMF) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Fedratinib (Inrebic) for ruxolitinib-resistant / intolerant PMF (REG-FEDRATINIB-PMF) 1/1 component drug(s) not on NSZU formulary | ✓ registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan Allogeneic hematopoietic cell transplant for high-risk PMF (REG-ALLOHCT-PMF) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-07-26.