Treatment plan — High-Grade B-Cell Lymphoma, Double-Hit / Triple-Hit

OpenOnco · DIS-HGBL-DH · Actionable biomarker present

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OpenOnco · Treatment Plan

Treatment plan — High-Grade B-Cell Lymphoma, Double-Hit / Triple-Hit

PLAN-VAR-HGBL-DH-BIOMARK-V1 · v1 · 2026-05-13

Patient

VAR-HGBL-DH-BIOMARK · Algorithm: ALGO-HGBL-DH-1L

DiagnosisHigh-Grade B-Cell Lymphoma, Double-Hit / Triple-Hit

MOH / ICD-10C83.3

ICD-O-39680/3

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
No clinically actionable variants matched in this profile.

⚠️ Not included in plan

Biomarker	Status
BIO-CD20-IHC	BIO definition in KB; no ESCAT BMA entry — verify with clinician

Primary current-line option

Aggressive plan

★ DEFAULT

Indication

IND-HGBL-DH-1L-RCHOP

Regimen

Rituximab + CHOP (R-CHOP), 6 cycles

Drugs + NSZU

Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 of each 21-day cycle · IV ✓ NSZU covered
Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 750 mg/m² · IV day 1 of each 21-day cycle · IV ⚠ NSZU — not for this indication
Doxorubicin (DRUG-DOXORUBICIN) 50 mg/m² · IV day 1 of each 21-day cycle · IV ✓ NSZU covered
Vincristine (DRUG-VINCRISTINE) 1.4 mg/m² (capped at 2 mg total) · IV day 1 of each 21-day cycle · IV ⚠ NSZU — not for this indication
Prednisone (DRUG-PREDNISONE) 100 mg · PO days 1-5 of each 21-day cycle · PO ⚠ NSZU — not for this indication

Supportive care

SUP-PJP-PROPHYLAXIS, SUP-TLS-PROPHYLAXIS, SUP-ANTIEMETIC-PREMED

Hard contraindications

CI-HBV-NO-PROPHYLAXIS, CI-LVEF-LOW-FOR-ANTHRACYCLINE

Reason

Primary current-line option selected by ALGO-HGBL-DH-1L at step 1.

Other current-line alternatives (1 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Standard plan

Indication

IND-HGBL-DH-1L-DAEPOCHR

Regimen

Dose-Adjusted EPOCH + Rituximab (DA-EPOCH-R), 6 cycles

Drugs + NSZU

Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV day 1 each cycle · IV ✓ NSZU covered
Etoposide (DRUG-ETOPOSIDE) 50 mg/m²/day · Continuous IV days 1-4 (96h infusion); dose adjust per ANC nadir prior cycle · IV ⚠ NSZU — not for this indication
Doxorubicin (DRUG-DOXORUBICIN) 10 mg/m²/day · Continuous IV days 1-4 (96h infusion); dose adjust · IV ✓ NSZU covered
Vincristine (DRUG-VINCRISTINE) 0.4 mg/m²/day (no cap) · Continuous IV days 1-4 (96h infusion) · IV ⚠ NSZU — not for this indication
Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 750 mg/m² (start; dose-adjusted up) · IV day 5 · IV ⚠ NSZU — not for this indication
Prednisone (DRUG-PREDNISONE) 60 mg/m² BID · PO days 1-5 · PO ⚠ NSZU — not for this indication

Supportive care

SUP-PJP-PROPHYLAXIS, SUP-TLS-PROPHYLAXIS, SUP-ANTIEMETIC-PREMED

Hard contraindications

CI-HBV-NO-PROPHYLAXIS, CI-LVEF-LOW-FOR-ANTHRACYCLINE

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	—	standard
TEST-BM-TREPHINE	Bone Marrow Trephine	Critical	histology	—	standard
TEST-CBC	Complete Blood Count with Differential	Critical	lab	—	all tracks
TEST-CD20-IHC	CD20 Immunohistochemistry	Critical	histology	CSD Lab ✓ (code TBC)	all tracks
TEST-CMP	Comprehensive Metabolic Panel	Critical	lab	—	all tracks
TEST-FISH-PANEL	FISH (Fluorescence In Situ Hybridization)	Critical	genomic	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	—	standard
TEST-HIV-SEROLOGY	HIV Antibody/Antigen	Critical	lab	—	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-LN-EXCISIONAL-BIOPSY	Excisional LN Biopsy	Critical	histology	—	standard
TEST-PREGNANCY	Beta-HCG	Critical	lab	—	standard
TEST-ECHO	Echocardiography	Standard	imaging	—	all tracks
TEST-PET-CT	FDG PET/CT (whole body)	Standard	imaging	—	all tracks

Red flags — PRO / CONTRA aggressive

PRO-AGGRESSIVE

Triggers that push toward the aggressive track

—

CONTRA-AGGRESSIVE

Hard contraindications to escalation

Active or latent HBV without antiviral prophylaxis is an absolute contraindication to starting B-cell-depleting / immunomodulatory monoclonal antibody therapy (anti-CD20, anti-CD30 ADC, anti-CD38). Severe HBV reactivation hepatitis risk including fulminant hepatic failure.CI-HBV-NO-PROPHYLAXIS
Pre-treatment LVEF <50% is an absolute contraindication to anthracycline-containing regimens (R-CHOP, Pola-R-CHP, ABVD, BV-AVD, etc.). Cardiotoxicity from doxorubicin is dose-cumulative and often irreversible; starting with already-impaired function risks acute decompensation.CI-LVEF-LOW-FOR-ANTHRACYCLINE

What NOT to do

Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity

Aggressive plan (IND-HGBL-DH-1L-RCHOP)

Do not prescribe R-CHOP if DA-EPOCH-R is accessible — outcome difference clinically significant.
Do not skip HBV screening + prophylaxis.
Do not forget about CAR-T pathway if relapse — early referral to CAR-T center.

Standard plan (IND-HGBL-DH-1L-DAEPOCHR)

Do not prescribe R-CHOP as 1L in known double-hit status — substantial OS difference.
Do not skip FISH break-apart MYC + BCL2 + BCL6 on ALL newly-diagnosed DLBCL — otherwise double-hit is missed.
Do not skip HBV screening + entecavir prophylaxis.
Do not prescribe without baseline LVEF ≥50%.
Do not skip CNS-IPI calculation + prophylaxis if high-risk.

Monitoring schedule

Monitoring schedule by treatment phase

Aggressive plan · MON-R-CHOP-REGIMEN

Phase	Window	Tests	Checkpoints
baseline	Within 2 weeks before cycle 1	TEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH, TEST-B2-MICROGLOBULIN, TEST-HBV-SEROLOGY, TEST-HCV-ANTIBODY, TEST-HIV-SEROLOGY, TEST-PET-CT, TEST-LN-EXCISIONAL-BIOPSY, TEST-FLOW-CYTOMETRY, TEST-CD20-IHC, TEST-ECHO, TEST-PREGNANCY, TEST-BM-ASPIRATE, TEST-BM-TREPHINE	Confirm CD20+ DLBCL histology; rule out double-hit (FISH for MYC/BCL2/BCL6) Confirm HBV status + entecavir prophylaxis plan if HBsAg+ or anti-HBc+ Baseline LVEF ≥50% before doxorubicin IPI calculation documented (age, ECOG, LDH, stage, extranodal sites) CNS-IPI calculation if anatomic risk sites or composite score concerning Fertility preservation discussion (sperm banking / oocyte cryo) for childbearing-age
on_treatment	Day 1 of every 21-day cycle	TEST-CBC, TEST-CMP, TEST-LFT	ANC ≥1500 + platelets ≥100K before each cycle (delay or G-CSF if not) Neuropathy grade documented (CTCAE) — vincristine modification if ≥2 LVEF re-check after cumulative doxorubicin ~300 mg/m²
interim_response_assessment	After cycles 2-4 (interim PET-CT)	TEST-PET-CT, TEST-LDH	Lugano response criteria + Deauville score If Deauville 4-5 with mass progression → consider salvage or trial
end_of_treatment	After cycle 6 (within 6-8 weeks)	TEST-PET-CT, TEST-CBC, TEST-CMP, TEST-LDH	Confirm CR vs PR vs SD vs PD by Lugano/Deauville Begin survivorship plan: cardiac surveillance schedule, vaccination catch-up, second-cancer screening
follow_up_short	Every 3 months × 2 years post-treatment	TEST-CBC, TEST-CMP, TEST-LFT, TEST-LDH	Surveillance for relapse (~40% relapse risk by 2 years overall) HBV reactivation monitoring continues for 12 months post anti-CD20
follow_up_long	Every 6 months years 3-5, then annually	TEST-CBC, TEST-LFT, TEST-ECHO	Late cardiomyopathy screening (LVEF) annually if cumulative dox >300 Annual second-malignancy screening (skin, breast, etc. age-appropriate)

Timeline

Treatment timeline — derived from regimen + monitoring schedule

Aggressive plan

Baseline

Within 2 weeks before cycle 1

Induction · Rituximab + CHOP (R-CHOP), 6 cycles

21-day cycles × 6 (with consideration of 2-month interim PET-CT after cycles 2-4)

Response assessment

After cycles 2-4 (interim PET-CT)

Follow-up

Every 3 months × 2 years post-treatment

Standard plan

Baseline

Within 2 weeks before cycle 1

Induction · Dose-Adjusted EPOCH + Rituximab (DA-EPOCH-R), 6 cycles

21-day cycles × 6 cycles for Burkitt; CNS prophylaxis IT MTX/cytarabine intercalated

Response assessment

After cycles 2-4 (interim PET-CT)

Follow-up

Every 3 months × 2 years post-treatment

MDT brief

Discussion questions (7, 4 blocking)

BLOCKING OQ-CD20-CONFIRMATION
Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated.
Anti-CD20 therapy is the backbone of most lines of treatment; absence of CD20 expression fully changes the regimen.
→ pathologist
OQ-STAGING-COMPLETE
Has complete staging been done (Lugano + PET/CT or CT)?
Prognosis and track selection depend on stage and tumor burden.
→ radiologist
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
BLOCKING OQ-BIOMARKER-BCL2-REARRANGEMENT
What is the status of BCL2 rearrangement (t(14;18) IGH/BCL2 by FISH break-apart) (BIO-BCL2-REARRANGEMENT)? It is required by track(s): IND-HGBL-DH-1L-RCHOP, IND-HGBL-DH-1L-DAEPOCHR. Expected value: positive (FISH) — classic MYC partner in HGBL-DH.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist
BLOCKING OQ-BIOMARKER-BCL6-REARRANGEMENT
What is the status of BCL6 rearrangement (3q27) by FISH break-apart (BIO-BCL6-REARRANGEMENT)? It is required by track(s): IND-HGBL-DH-1L-RCHOP, IND-HGBL-DH-1L-DAEPOCHR. Expected value: positive (FISH) — alternative MYC partner.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist
BLOCKING OQ-BIOMARKER-MYC-REARRANGEMENT
What is the status of MYC rearrangement (8q24) by FISH break-apart (BIO-MYC-REARRANGEMENT)? It is required by track(s): IND-HGBL-DH-1L-RCHOP, IND-HGBL-DH-1L-DAEPOCHR. Expected value: positive (FISH break-apart) — HGBL-DH classification requires MYC-rearrangement.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist
OQ-BIOMARKER-DOUBLE-HIT
What is the status of Double-hit (MYC + BCL2 and/or BCL6 rearrangements) (BIO-DOUBLE-HIT)? It is required by track(s): IND-HGBL-DH-1L-DAEPOCHR. Expected value: positive.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist

MDT talk tree (8 steps)

#	Owner	Topic	Action
1	molecular_geneticist	Biomarker status BLOCKING	What is the status of BCL2 rearrangement (t(14;18) IGH/BCL2 by FISH break-apart) (BIO-BCL2-REARRANGEMENT)? It is required by track(s): IND-HGBL-DH-1L-RCHOP, IND-HGBL-DH-1L-DAEPOCHR. Expected value: positive (FISH) — classic MYC partner in HGBL-DH.
2	molecular_geneticist	Biomarker status BLOCKING	What is the status of BCL6 rearrangement (3q27) by FISH break-apart (BIO-BCL6-REARRANGEMENT)? It is required by track(s): IND-HGBL-DH-1L-RCHOP, IND-HGBL-DH-1L-DAEPOCHR. Expected value: positive (FISH) — alternative MYC partner.
3	molecular_geneticist	Biomarker status BLOCKING	What is the status of MYC rearrangement (8q24) by FISH break-apart (BIO-MYC-REARRANGEMENT)? It is required by track(s): IND-HGBL-DH-1L-RCHOP, IND-HGBL-DH-1L-DAEPOCHR. Expected value: positive (FISH break-apart) — HGBL-DH classification requires MYC-rearrangement.
4	pathologist	Pathology confirmation BLOCKING	Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated.
5	hematologist	Staging / disease burden	What is the current LDH? Marker of tumor burden and transformation.
6	molecular_geneticist	Biomarker status	What is the status of Double-hit (MYC + BCL2 and/or BCL6 rearrangements) (BIO-DOUBLE-HIT)? It is required by track(s): IND-HGBL-DH-1L-DAEPOCHR. Expected value: positive.
7	radiologist	Staging / disease burden	Has complete staging been done (Lugano + PET/CT or CT)?
8	clinical_pharmacist	Specialist review	Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.

Skills (required) — mandatory virtual specialists (1)

Hematologist / oncohematologist required
Lymphoma diagnosis — leading specialty for treatment management.
Owns: OQ-LDH-CURRENT

Skills (recommended) — for consideration (3)

Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Owns: OQ-BIOMARKER-BCL2-REARRANGEMENT, OQ-BIOMARKER-BCL6-REARRANGEMENT, OQ-BIOMARKER-MYC-REARRANGEMENT, OQ-BIOMARKER-DOUBLE-HIT
Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-CD20-CONFIRMATION

Data quality

Incomplete for default-track review. Default-track review is incomplete until required biomarker gaps are resolved.

Biomarker coverage: 1/5 known (20%), 4 missing, 3 default-track gaps
Missing critical: cd20_ihc_status, lugano_stage
Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
Unevaluated RedFlags: RF-HGBL-DH-CNS-PROPHYLAXIS-TRIGGER, RF-HGBL-DH-EMERGENCY-TLS, RF-HGBL-DH-HIGH-RISK-BIOLOGY, RF-HGBL-DH-ORGAN-DYSFUNCTION, RF-HGBL-DH-TRANSFORMATION-PROGRESSION

Missing data for doctor action

Priority	Clinical item	Owner	Why it matters	Next action	Blocks
CRITICAL	CD20 IHC status `cd20_ihc_status`	pathologist	Confirms CD20-directed therapy is biologically appropriate.	Verify CD20 IHC result, specimen, method, and report date.	-
CRITICAL	Lugano stage `lugano_stage`	radiologist	Defines lymphoma extent and supports tumor-burden and response-assessment decisions.	Document Lugano stage from PET/CT or contrast CT staging.	-
RECOMMENDED	LDH ratio to ULN `ldh_ratio_to_uln`	medical_oncologist	Supports prognostic scoring and aggressive-biology flags.	Enter LDH with local upper limit of normal.	-
RECOMMENDED	FIB-4 liver fibrosis index `fib4_index`	infectious_disease_hepatology	Screens hepatic fibrosis risk before hepatotoxic therapy or antiviral coordination.	Calculate FIB-4 from age, AST, ALT, and platelet count.	-
RECOMMENDED	PET/CT date `pet_ct_date`	radiologist	Shows whether baseline staging is recent enough for treatment planning and later response comparison.	Document baseline PET/CT date or explain alternative staging modality.	-

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-BCL2-REARRANGEMENT`	BCL2 rearrangement (t(14;18) IGH/BCL2 by FISH break-apart)	molecular_geneticist	yes	IND-HGBL-DH-1L-RCHOP, IND-HGBL-DH-1L-DAEPOCHR	Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive (FISH) — classic MYC partner in HGBL-DH
`BIO-BCL6-REARRANGEMENT`	BCL6 rearrangement (3q27) by FISH break-apart	molecular_geneticist	yes	IND-HGBL-DH-1L-RCHOP, IND-HGBL-DH-1L-DAEPOCHR	Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive (FISH) — alternative MYC partner
`BIO-MYC-REARRANGEMENT`	MYC rearrangement (8q24) by FISH break-apart	molecular_geneticist	yes	IND-HGBL-DH-1L-RCHOP, IND-HGBL-DH-1L-DAEPOCHR	Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive (FISH break-apart) — HGBL-DH classification requires MYC-rearrangement
`BIO-DOUBLE-HIT`	Double-hit (MYC + BCL2 and/or BCL6 rearrangements)	molecular_geneticist	no	IND-HGBL-DH-1L-DAEPOCHR	Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive

Technical MDT skill metadata (4/16 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-LYMPHOMA-2025: Lymphomas: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up (2025)
SRC-NCCN-BCELL-2025: NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (v.2.2025)

Experimental options (clinical trials)

Last synced: 2026-05-13 · 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 Rituximab + CHOP (R-CHOP), 6 cycles (REG-R-CHOP)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary
Standard plan Dose-Adjusted EPOCH + Rituximab (DA-EPOCH-R), 6 cycles (REG-DA-EPOCH-R)	✓ registered	✓ covered	₴-? — verify pathway	NSZU formulary

Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-13.

plan_id: PLAN-VAR-HGBL-DH-BIOMARK-V1 | version: 1 | generated: 2026-05-13T10:01:52.100021+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.