Patient
PV-HR-1L-001 · Algorithm: ALGO-PV-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, JH2 pseudokinase domain — present in ~95% of polycythemia vera) | IA | Molecular evidence option Trial or research option - SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| JAK2 V617F is the defining driver of polycythemia vera (~95%) and a WHO 2022 / ICC 2022 major diagnostic criterion (per SRC-NCCN-MPN-2025, SRC-ESMO-MPN-2015). Treatment is risk-stratified, not variant-genotype directed: low-risk PV → phlebotomy + low-dose aspirin; high-risk PV (age ≥60 or prior thrombosis) → cytoreduction with hydroxyurea or interferon-alpha (ropeginterferon-alfa-2b, PROUD-PV / CONTINUATION-PV Gisslinger 2020 — superior molecular response and event-free survival at 5y vs hydroxyurea); ruxolitinib (RESPONSE Vannucchi 2015 — 21% CHR + spleen response vs 1% best available therapy) for hydroxyurea- intolerant or -resistant disease. | phlebotomy + low-dose aspirin (low-risk PV per SRC-NCCN-MPN-2025)
hydroxyurea (high-risk 1L cytoreduction per SRC-NCCN-MPN-2025, SRC-ESMO-MPN-2015)
ropeginterferon alfa-2b (high-risk; preferred for younger patients per SRC-PROUD-PV-GISSLINGER-2020)
ruxolitinib (post-hydroxyurea resistance/intolerance per SRC-RESPONSE-VANNUCCHI-2015) | - SRC-NCCN-MPN-2025
- SRC-ESMO-MPN-2015
- SRC-RESPONSE-VANNUCCHI-2015
- SRC-PROUD-PV-GISSLINGER-2020
|
Primary current-line option
- Indication
- IND-PV-1L-HU
- Regimen
- Hydroxyurea (PV / ET high-risk 1L cytoreduction) + baseline phlebotomy/ASA
- Drugs + NSZU
- Hydroxyurea (DRUG-HYDROXYUREA) Start 500-1500 mg/day PO (15-25 mg/kg/day); titrate to target · continuous PO daily; titrate by CBC q2-4wk initially, then q1-3 mo once stable · PO ✓ NSZU covered
- Aspirin (DRUG-ASPIRIN) 81-100 mg PO daily (low-dose aspirin) · continuous · PO ⚠ Out-of-pocket
- Reason
- Primary current-line option selected by ALGO-PV-1L at step 1; branch-driving red flag: RF-PV-ET-HIGH-THROMBOSIS-RISK.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-PV-1L-PHLEBOTOMY-ASA
- Regimen
- Hydroxyurea (PV / ET high-risk 1L cytoreduction) + baseline phlebotomy/ASA
- Drugs + NSZU
- Hydroxyurea (DRUG-HYDROXYUREA) Start 500-1500 mg/day PO (15-25 mg/kg/day); titrate to target · continuous PO daily; titrate by CBC q2-4wk initially, then q1-3 mo once stable · PO ✓ NSZU covered
- Aspirin (DRUG-ASPIRIN) 81-100 mg PO daily (low-dose aspirin) · continuous · PO ⚠ Out-of-pocket
- 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 1 → branch IND-PV-1L-HU
- RF-PV-ET-HIGH-THROMBOSIS-RISK ★ winner: PV or ET high-risk for thrombosis: age >60 OR prior arterial / venous thrombosis OR (ET only) JAK2 V617F + CV risk factors (IPSET-thrombosis high) — triggers cytoreduction (HU 1L) in addition to baseline phlebotomy + ASA SRC-NCCN-MPN-2025SRC-ESMO-MPN-2015SRC-RESPONSE-VANNUCCHI-2015
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-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-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 | — | aggressive |
| TEST-IRON-PANEL | Iron Panel | Standard | lab | — | all tracks |
| TEST-RETICULOCYTE | Reticulocyte Count | Standard | lab | — | all tracks |
| TEST-URIC-ACID | Serum Uric Acid | Standard | lab | — | all tracks |
| TEST-D-DIMER | D-Dimer | Desired | lab | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- PV or ET high-risk for thrombosis: age >60 OR prior arterial / venous thrombosis OR (ET only) JAK2 V617F + CV risk factors (IPSET-thrombosis high) — triggers cytoreduction (HU 1L) in addition to baseline phlebotomy + ASARF-PV-ET-HIGH-THROMBOSIS-RISK
- PV or ET patient with organ dysfunction limiting cytoreductive choice: severe renal impairment (CrCl <30 — limits HU), severe hepatic dysfunction (limits ruxolitinib), or severe cardiac dysfunction (limits anagrelide)RF-PV-ET-ORGAN-DYSFUNCTION
- PV or ET patient pregnant or planning pregnancy — HU and anagrelide contraindicated; switch to interferon-α (PEG-IFN-α2a or ropeginterferon)RF-PV-ET-PREGNANCY-OR-PLANNING
- PV resistant or intolerant to hydroxyurea per ELN criteria: persistent need for phlebotomy on HU 2 g/day, persistent symptoms, splenomegaly progression, cytopenias at minimum effective HU dose, or HU-related cutaneous ulcers — switch to ruxolitinib (RESPONSE)RF-PV-HU-RESISTANCE-INTOLERANCE
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-PV-1L-HU)
- Do not skip ELN-criteria for HU-resistance/intolerance — quickly escalate to ruxolitinib (RESPONSE) on response.
- Do not prescribe HU in patients with cutaneous ulceration history — ulcer recurrence likely.
- Do not skip monthly CBC for the first 3 months — myelosuppression-titrating.
- Do not prescribe HU in pregnancy / pregnancy plans — switch to IFN-α.
- Do not combine with peg-IFN-α without a clear protocol — dosing of both changes.
Standard plan (IND-PV-1L-PHLEBOTOMY-ASA)
- Do not skip JAK2 V617F testing — diagnostic criterion + may escalate risk score.
- Do not prescribe ASA in extreme thrombocytosis (plt >1500K) without ruling out acquired vWD — bleeding risk.
- Do not skip abdominal vein thrombosis screening at presentation — atypical presentation in PV.
- Do not prescribe iron supplementation for iron-deficiency from phlebotomy without a clear clinical cause — this is a desired effect.
- Do not use full-dose ASA (325 mg) — low-dose (81-100 mg) equally effective with lower bleeding risk.
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-PV-ET-FRAILTY-AGE, RF-PV-ET-HIGH-THROMBOSIS-RISK, RF-PV-ET-INFECTION-SCREENING, RF-PV-ET-ORGAN-DYSFUNCTION, RF-PV-ET-PREGNANCY-OR-PLANNING, RF-PV-HU-RESISTANCE-INTOLERANCE
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-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)
- SRC-PROUD-PV-GISSLINGER-2020: Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study (2020)
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 |
|---|
| Aggressive plan Hydroxyurea (PV / ET high-risk 1L cytoreduction) + baseline phlebotomy/ASA (REG-HU-PV-ET) 1/2 component drug(s) not on NSZU formulary | ✓ registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Standard plan Hydroxyurea (PV / ET high-risk 1L cytoreduction) + baseline phlebotomy/ASA (REG-HU-PV-ET) 1/2 component drug(s) not on NSZU formulary | ✓ registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-06-11.