OpenOnco · Treatment Plan

Treatment plan — DIS-HCL

PLAN-BMA-MAP2K1_HCL-V1 · v1 · 2026-05-04

Patient

BMA-MAP2K1_HCL · 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-MAP2K1	MAP2K1 activating mutation (K57E, Q56P, E203K) — hairy cell leukemia variant (HCL-V); by definition BRAF V600E-negative	IIA	SRC-NCCN-AML-2025: Level Category 2B (Supports, Sensitivity/Response)	Hairy cell leukemia variant (HCL-V) is a rare splenic B-cell lymphoma (~10% of HCL cases) that is BRAF V600E-negative (in contrast to classic HCL where BRAF V600E is present in ~100%). MAP2K1 (MEK1) activating mutations are detected in ~40–50% of HCL-V cases and represent an alternative MAPK pathway activation mechanism. Unlike classic HCL (where vemurafenib or cladribine + rituximab are standard), HCL-V responds poorly to BRAF inhibitors and less well to purine analogues. Small series and case reports document activity of MEK inhibitors (cobimetinib, trametinib) in MAP2K1-mutant HCL-V: ORRs of 50–80% in heavily pretreated patients. No phase III RCT; no FDA approval. NCCN lists MEK inhibitors as Category 2B for HCL-V with MAP2K1 mutation. Pentostatin + rituximab remains standard first-line for HCL-V. MAP2K1 testing recommended in all HCL-V to guide salvage therapy.	cobimetinib 60 mg PO QD (days 1–21 of 28-day cycle) — investigational for MAP2K1-mutant HCL-V; evidence from small series only trametinib 2 mg PO QD — alternative MEK inhibitor; same investigational status pentostatin 4 mg/m² IV q2w + rituximab 375 mg/m² IV — standard first-line HCL-V (not biomarker-driven)	SRC-NCCN-AML-2025

Treatment options (2 tracks)

Standard plan

★ DEFAULT

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

Engine default per algorithm ALGO-HCL-1L: {'step': 2, 'outcome': False, 'branch': {'result': 'IND-HCL-1L-CLADRIBINE'}, 'fired_red_flags': [], 'winner_red_flag': None}

Aggressive plan

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

Alternative track 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

Skills (recommended) — for consideration (1)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD

Open questions (1, 0 blocking)

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

Data quality

Unevaluated RedFlags: RF-HCL-FRAILTY-AGE, RF-HCL-HIGH-RISK-BIOLOGY, RF-HCL-INFECTION-SCREENING, RF-HCL-TRANSFORMATION-PROGRESSION

Skill catalog (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	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	cellular_therapy

Sources cited

SRC-MOZ-UA-LYMPH-2013: Уніфікований клінічний 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)

Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-05-04.

NCT	Title	Phase	Status	Sponsor	UA	Eligibility (excerpt)
NCT04324112	Encorafenib Plus Binimetinib for People With BRAF V600 Mutated Relapsed/Refractory HCL	PHASE2	RECRUITING	National Cancer Institute (NCI)	—
NCT04322383	Binimetinib for People With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant	PHASE2	RECRUITING	National Cancer Institute (NCI)	—

Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.

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
Trial · NCT04324112 Encorafenib Plus Binimetinib for People With BRAF V600 Mutated Relapsed/Refractory HCL No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04322383 Binimetinib for People With Relapsed/Refractory BRAF Wild Type Hairy Cell Leukemia and Variant No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.

plan_id: PLAN-BMA-MAP2K1_HCL-V1 | version: 1 | generated: 2026-05-04T14:13:16.624771+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.