Patient
PMF-INT2-RUX-001 · Algorithm: ALGO-PMF-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 |
|---|
| 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-1L-OBSERVATION
- Regimen
- Ruxolitinib (PMF — symptomatic splenomegaly / constitutional symptoms)
- Drugs + NSZU
- Ruxolitinib (DRUG-RUXOLITINIB) Start by baseline platelet count: plt 50-100K → 5 mg BID; 100-200K → 15 mg BID; >200K → 20 mg BID. Titrate by toxicity (max 25 mg BID). · continuous PO twice daily; NEVER abrupt-stop (taper) · PO ✓ NSZU covered
- Supportive care
- SUP-HBV-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS
- Reason
- Primary current-line option selected by ALGO-PMF-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-PMF-1L-RUXOLITINIB
- Regimen
- Ruxolitinib (PMF — symptomatic splenomegaly / constitutional symptoms)
- Drugs + NSZU
- Ruxolitinib (DRUG-RUXOLITINIB) Start by baseline platelet count: plt 50-100K → 5 mg BID; 100-200K → 15 mg BID; >200K → 20 mg BID. Titrate by toxicity (max 25 mg BID). · continuous PO twice daily; NEVER abrupt-stop (taper) · PO ✓ NSZU covered
- Supportive care
- SUP-HBV-PROPHYLAXIS, SUP-HSV-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-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-CMV-SEROLOGY | CMV IgG/IgM | Standard | lab | — | aggressive |
| TEST-IRON-PANEL | Iron Panel | Standard | lab | — | all tracks |
| TEST-RETICULOCYTE | Reticulocyte Count | Standard | lab | — | all tracks |
| TEST-D-DIMER | D-Dimer | Desired | lab | — | standard |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Primary myelofibrosis with DIPSS-Plus intermediate-2 or high risk — alloHCT referral mandatory in eligible patients (only curative option); ruxolitinib for symptom + spleen control while awaiting transplantRF-DIPSS-PLUS-HIGH
- PMF with anemia as dominant clinical problem (Hb <10 g/dL OR transfusion-dependent) — momelotinib preferred over ruxolitinib (MOMENTUM trial: spleen + symptom + Hb improvement)RF-PMF-ANEMIA-DOMINANT
- 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-phaseRF-PMF-BLAST-PROGRESSION
- 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)RF-PMF-FRAILTY-AGE
- 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 transplantRF-PMF-HIGH-RISK-DIPSS
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-PMF-1L-OBSERVATION)
- Do not skip DIPSS-Plus / MIPSS70 risk-stratification at presentation — critical for long-term planning.
- Do not prescribe ruxolitinib to asymptomatic patients — change in natural history not proven; toxicity + cost are unnecessary.
- Do not skip pre-JAKi HBV / TB screening + active prophylaxis.
- Do not abrupt-stop ruxolitinib — taper over 1-2 weeks.
- Do not skip alloHCT discussion for intermediate-2 / high — switch to aggressive-track indication via RF.
Aggressive plan (IND-PMF-1L-RUXOLITINIB)
- Do not abrupt-stop ruxolitinib — taper over 1-2 weeks; cytokine rebound may be life-threatening.
- Do not skip pre-JAKi HBV / TB / HSV screening + active prophylaxis.
- Do not skip alloHCT discussion for transplant-eligible — JAKi does not cure MF.
- Do not use full ruxolitinib dose at plt 50-100K — start at 5 mg BID + titrate.
- Do not combine with strong CYP3A4 inhibitor without dose reduction (50%).
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-DIPSS-PLUS-HIGH, RF-PMF-ANEMIA-DOMINANT, 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 (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-COMFORT-I-VERSTOVSEK-2012: A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis (2012)
- 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-NCCN-MPN-2025: NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms (v.X.2025)
Experimental options (clinical trials)
Last synced: 2026-06-11 · 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 Ruxolitinib (PMF — symptomatic splenomegaly / constitutional symptoms) (REG-RUX-PMF) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Ruxolitinib (PMF — symptomatic splenomegaly / constitutional symptoms) (REG-RUX-PMF) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-06-11.