Patient
HCL-TYPICAL-001 · Algorithm: ALGO-HCL-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-BRAF-V600E | V600E | IB | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Poor Outcome)
Resistance or avoidance signal Trial or research option - SRC-CIVIC: Level C (Supports, Sensitivity/Response)
- SRC-CIVIC: Level D (Supports, Sensitivity/Response)
| BRAF V600E is the defining molecular lesion of classic hairy cell leukemia (~100% of cHCL; absent in HCL-variant). Vemurafenib monotherapy yields CR ~35% / ORR ~96% in relapsed/refractory cHCL (Tiacci et al. NEJM 2015). Vemurafenib + rituximab gives durable CR in ~87% (Tiacci et al. NEJM 2021). Dabrafenib + trametinib also active. Used as salvage after purine-analog failure or in cladribine-ineligible patients. | vemurafenib monotherapy (R/R cHCL)
vemurafenib + rituximab (consolidation / R/R)
dabrafenib + trametinib (alternative) | |
Primary current-line option
- Indication
- IND-HCL-1L-CLADRIBINE
- Regimen
- Cladribine single 7-day course
- Drugs + NSZU
- Cladribine (DRUG-CLADRIBINE) 0.09 mg/kg/day continuous IV · × 7 days, single course · IV ⚠ NSZU — not for this indication
- Supportive care
- SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS
- Reason
- Primary current-line option selected by ALGO-HCL-1L at step 2.
Other current-line alternatives (1 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-HCL-1L-PENTOSTATIN
- Regimen
- Cladribine single 7-day course
- Drugs + NSZU
- Cladribine (DRUG-CLADRIBINE) 0.09 mg/kg/day continuous IV · × 7 days, single course · IV ⚠ NSZU — not for this indication
- Supportive care
- SUP-PJP-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-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-CECT-CAP | CECT chest/abdomen/pelvis | Critical | imaging | — | all tracks |
| TEST-CMP | Comprehensive Metabolic 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 | — | standard |
| TEST-HIV-SEROLOGY | HIV Antibody/Antigen | Critical | lab | — | standard |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-PERIPHERAL-SMEAR | Peripheral Blood Smear | Critical | lab | CSD Lab ✓ (code TBC) | all tracks |
| TEST-NGS-LYMPHOID-PANEL | Lymphoid NGS Panel | Desired | genomic | CSD Lab ✓ (code TBC) | standard |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Age >75 + ECOG ≥2 OR significant comorbidity — pentostatin's weekly schedule allows finer toxicity titration than cladribine 5-7 day continuous infusion; preferred for fragile patients.RF-HCL-FRAILTY-AGE
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-HCL-1L-CLADRIBINE)
- Do not start in active uncontrolled infection — deep CD4 lymphopenia will significantly increase the risk.
- Do not skip PJP + HSV prophylaxis for ≥1 year post-treatment.
- Do not skip BRAF V600E testing — required for second-line targeted therapy at relapse.
- Do not treat asymptomatic HCL without cytopenia / splenomegaly indication.
Aggressive plan (IND-HCL-1L-PENTOSTATIN)
- Do not prescribe in severe renal impairment without dose adjustment.
- Do not skip PJP + HSV prophylaxis.
Monitoring schedule
Monitoring schedule by treatment phase
Standard plan · MON-HCL-CLADRIBINE
| Phase | Window | Tests | Checkpoints |
|---|
| baseline | Within 1 week before start | TEST-CBC, TEST-CMP, TEST-LFT, TEST-PERIPHERAL-SMEAR, TEST-BM-ASPIRATE, TEST-BM-TREPHINE, TEST-FLOW-CYTOMETRY, TEST-CECT-CAP | - Confirm HCL: hairy cells on PB smear, BM trephine annexin-A1+, flow CD11c+CD25+CD103+CD123+
- Document BRAF V600E status (informational; required for second-line targeted therapy if relapse)
- Treatment indication confirmed (significant cytopenia or symptomatic splenomegaly)
|
| post_treatment_immediate | Weeks 2-4 post-cladribine | TEST-CBC | - Febrile neutropenia management; transfusion support as needed
|
| response_assessment | Month 4-6 post-cladribine | TEST-CBC, TEST-PERIPHERAL-SMEAR, TEST-BM-ASPIRATE, TEST-BM-TREPHINE, TEST-FLOW-CYTOMETRY | - CR / PR / persistent disease; if persistent — repeat cladribine course or rituximab consolidation
|
| follow_up | Every 6 months × 5 years, then annually | TEST-CBC, TEST-CMP | - Surveillance for relapse (median PFS >10 years; relapse can occur)
- PJP + HSV prophylaxis continuing ≥1 year
|
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Baseline
Within 1 week before start
Induction · Cladribine single 7-day course
7-day cycles × 1 (single course; repeat only if persistent disease at 6 months)
Response assessment
Month 4-6 post-cladribine
Follow-up
Every 6 months × 5 years, then annually
MDT brief
Discussion questions (2, 1 blocking)
BLOCKING OQ-HBV-SEROLOGY
Has HBV serology (HBsAg, anti-HBc total) been done? Status must be known before starting anti-CD20 therapy.
Anti-CD20 without HBV prophylaxis in HBsAg+/anti-HBc+ patients carries significant reactivation risk (CI-HBV-NO-PROPHYLAXIS).
→ infectious_disease_hepatology
OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist
MDT talk tree (3 steps)
| # | Owner | Topic | Action |
|---|
| 1 | infectious_disease_hepatology | Infection / hepatic safety BLOCKING | Has HBV serology (HBsAg, anti-HBc total) been done? Status must be known before starting anti-CD20 therapy. |
| 2 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 3 | 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-HCL-FRAILTY-AGE, RF-HCL-HIGH-RISK-BIOLOGY, RF-HCL-INFECTION-SCREENING, RF-HCL-ORGAN-DYSFUNCTION, RF-HCL-TRANSFORMATION-PROGRESSION
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-MOZ-UA-LYMPH-2013: Уnoфікований кліnoчний протокол первинної, вторинної (спеціалізованої) медичної допомоги: Лімфоми (2013-10-30 (Наказ МОЗ України № 866))
- SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)
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 Cladribine single 7-day course (REG-CLADRIBINE-SINGLE) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Cladribine single 7-day course (REG-CLADRIBINE-SINGLE) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-06-11.