Patient
ET-HR-1L-001 · Algorithm: ALGO-ET-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 essential thrombocythemia) | IA | Molecular evidence option Trial or research option - SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| JAK2 V617F is one of three defining drivers in essential thrombocythemia (~50-60%; CALR ~25-30%, MPL ~3-5%, triple-negative ~10-15%) and a WHO 2022 / ICC 2022 major diagnostic criterion (per SRC-NCCN-MPN-2025, SRC-ESMO-MPN-2015). Treatment is risk-stratified by IPSET-thrombosis (age, prior thrombosis, JAK2 V617F positivity, cardiovascular risk factors); high-risk → cytoreduction with hydroxyurea (PT1 trial Harrison 2005 — superior thrombosis-free survival vs anagrelide in HU-naive ET); low-risk → low-dose aspirin alone (or observation in CALR-mutated very-low-risk per SRC-ESMO-MPN-2015). | low-dose aspirin (low-risk per SRC-NCCN-MPN-2025)
hydroxyurea + aspirin (high-risk 1L per SRC-PT1-HARRISON-2005)
interferon-alpha (preferred for younger high-risk per SRC-NCCN-MPN-2025, SRC-ESMO-MPN-2015)
anagrelide (HU-resistant/intolerant 2L) | - SRC-NCCN-MPN-2025
- SRC-ESMO-MPN-2015
- SRC-PT1-HARRISON-2005
|
Primary current-line option
- Indication
- IND-ET-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-ET-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-ET-1L-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-ET-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-ECHO | Echocardiography | Standard | imaging | — | desired (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 | — | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- ET transformation to post-ET myelofibrosis (~5-10% over 15 years) or to AML / MDS (rare ~1-5%): rising LDH, new splenomegaly, leukoerythroblastic smear, increasing reticulin fibrosis on trephine, blast appearance — re-stage, switch to MF or AML algorithmRF-ET-TRANSFORMATION-PROGRESSION
- PV or ET patient elderly or frail (age ≥80, ECOG ≥3, multiple comorbidities, life expectancy <5 years) — gentler cytoreduction (lower HU dose), expanded transfusion + monitoring strategyRF-PV-ET-FRAILTY-AGE
- 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
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-ET-1L-HU)
- Do not prescribe HU during pregnancy / pregnancy plans — switch to IFN-α.
- Do not skip monthly CBC for the first 3 months — myelosuppression-titrating.
- Do not use anagrelide 1L — PT-1 trial showed HU advantage on arterial thrombosis and MF progression.
- Do not prescribe in cutaneous ulceration history — risk of recurrence.
- Do not combine with peg-IFN without a clear protocol.
Standard plan (IND-ET-1L-ASA)
- Do not skip JAK2 / CALR / MPL testing — driver-mutation status determines subtype + IPSET-thrombosis risk.
- Do not prescribe ASA in extreme thrombocytosis (plt >1500K) without ruling out acquired vWD — check ristocetin cofactor activity.
- Do not skip prefibrotic-PMF differential on trephine — same presentation, worse prognosis.
- Do not prescribe anagrelide 1L — PT-1 trial showed lower cardiovascular profile + HU more preferable.
- Do not use full-dose ASA — low-dose is standard.
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-ET-HU-RESISTANT-INTOLERANT, RF-ET-TRANSFORMATION-PROGRESSION, 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
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)
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.