Patient
SMZL-HCVNEG-001 · Algorithm: ALGO-SMZL-1L
Etiological driver
Etiological driver · etiologically_driven archetype
Splenic Marginal Zone Lymphoma
- Hepatitis C virus (HCV) infection — etiologically associated in 10-30% (geographic variation)
- Splenic localization of marginal zone B-cells
- Frequent del(7q) cytogenetic abnormality
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 |
|---|
| No clinically actionable variants matched in this profile. |
| Biomarker | Status |
|---|
| BIO-CD20-IHC | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
Primary current-line option
- Indication
- IND-SMZL-1L-RITUXIMAB
- Regimen
- Rituximab monotherapy (375 mg/m² weekly × 4, then maintenance)
- Drugs + NSZU
- Rituximab (DRUG-RITUXIMAB) 375 mg/m² · IV weekly × 4 (induction); then every 2 months × 2 years (maintenance) · IV ✓ NSZU covered
- Hard contraindications
- CI-HBV-NO-PROPHYLAXIS
- Reason
- Primary current-line option selected by ALGO-SMZL-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-SMZL-1L-HCV-POSITIVE
- Regimen
- Sofosbuvir/Velpatasvir 12 weeks
- Drugs + NSZU
- Sofosbuvir/Velpatasvir (DRUG-SOFOSBUVIR-VELPATASVIR) 400/100 mg PO · once daily · PO ⚠ NSZU — not for this indication
- 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-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CD20-IHC | CD20 Immunohistochemistry | Critical | histology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-CECT-CAP | CECT chest/abdomen/pelvis | Critical | imaging | — | aggressive |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | aggressive |
| 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-HCV-ANTIBODY | HCV Antibody | Critical | lab | — | aggressive |
| 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-PET-CT | FDG PET/CT (whole body) | Standard | imaging | — | standard |
| TEST-FIB4 | FIB-4 Index (Fibrosis-4) | Calculation | clinical_assessment | — | standard |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- Decompensated cirrhosis (Child-Pugh B or C): ascites, encephalopathy, variceal bleeding, or jaundice from cirrhosisRF-DECOMP-CIRRHOSIS
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
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-SMZL-1L-RITUXIMAB)
- Do not start without HBV screening + entecavir prophylaxis if HBsAg+ or anti-HBc+ — anti-CD20 reactivation risk.
- Do not skip HCV testing — if HCV+, first DAA pathway (IND-SMZL-1L-HCV-POSITIVE).
- Do not prescribe splenectomy as 1L without discussing rituximab with the patient.
Standard plan (IND-SMZL-1L-HCV-POSITIVE)
- Do not skip HCV testing in all patients with SMZL — DAA may avoid chemoimmunotherapy.
- Do not combine sofosbuvir with amiodarone — risk of severe bradycardia.
- Do not skip HBV serology before start — occult reactivation possible.
Monitoring schedule
Monitoring schedule by treatment phase
Aggressive plan · MON-RITUXIMAB-MONO
| Phase | Window | Tests | Checkpoints |
|---|
| baseline | Within 2 weeks before first dose | TEST-CBC, TEST-LFT, TEST-LDH, TEST-CD20-IHC, TEST-HBV-SEROLOGY, TEST-HCV-ANTIBODY, TEST-FLOW-CYTOMETRY | - Confirm CD20+ histology
- HBV status + entecavir prophylaxis if HBsAg+ or anti-HBc+
|
| induction | Day 1 of each weekly induction × 4 | TEST-CBC, TEST-LFT | - Infusion reactions especially first dose
|
| maintenance | Every 2 months × 2 years | TEST-CBC, TEST-LFT, TEST-LDH | - HBV-DNA quarterly during therapy and 12 mo post
- Disease assessment clinically; imaging if concern
|
| follow_up | Every 6 months × 5 years post-treatment | TEST-CBC, TEST-LFT, TEST-LDH | - Surveillance for relapse + transformation
|
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Baseline
Within 2 weeks before first dose
Induction · Rituximab monotherapy (375 mg/m² weekly × 4, then maintenance)
7-day cycles × 4 weekly + 12 maintenance doses every 2 months × 2 years
Maintenance
Every 2 months × 2 years
Follow-up
Every 6 months × 5 years post-treatment
Standard plan
Induction · Sofosbuvir/Velpatasvir 12 weeks
84-day cycles × 1 (continuous 12-week course)
MDT brief
Discussion questions (6, 2 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
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
OQ-BIOMARKER-HCV-RNA
What is the status of HCV RNA (quantitative PCR) (BIO-HCV-RNA)? It is required by track(s): IND-SMZL-1L-HCV-POSITIVE. Expected value: detectable (positive viral load — confirms active HCV infection driving SMZL clonal proliferation; required to commit to DAA-first track).
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.
→ infectious_disease_hepatology
OQ-BIOMARKER-HCV-STATUS
What is the status of HCV status (anti-HCV antibody screening) (BIO-HCV-STATUS)? It is required by track(s): IND-SMZL-1L-HCV-POSITIVE. Expected value: anti-HCV-positive (categorical screen — pairs with BIO-HCV-RNA confirmation; antibody alone insufficient for treatment decision).
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.
→ medical_oncologist
MDT talk tree (7 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 | pathologist | Pathology confirmation BLOCKING | Is CD20+ status confirmed by histology (IHC)? Without CD20+, rituximab/obinutuzumab are not indicated. |
| 3 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 4 | infectious_disease_hepatology | Biomarker status | What is the status of HCV RNA (quantitative PCR) (BIO-HCV-RNA)? It is required by track(s): IND-SMZL-1L-HCV-POSITIVE. Expected value: detectable (positive viral load — confirms active HCV infection driving SMZL clonal proliferation; required to commit to DAA-first track). |
| 5 | medical_oncologist | Biomarker status | What is the status of HCV status (anti-HCV antibody screening) (BIO-HCV-STATUS)? It is required by track(s): IND-SMZL-1L-HCV-POSITIVE. Expected value: anti-HCV-positive (categorical screen — pairs with BIO-HCV-RNA confirmation; antibody alone insufficient for treatment decision). |
| 6 | radiologist | Staging / disease burden | Has complete staging been done (Lugano + PET/CT or CT)? |
| 7 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
Skills (required) — mandatory virtual specialists (1)
Skills (recommended) — for consideration (2)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-CD20-CONFIRMATION
Data quality
Incomplete for MDT sign-off. MDT sign-off is incomplete until critical clinical data gaps are resolved.
- Biomarker coverage: 1/3 known (33%), 2 missing, 0 default-track gaps
- Missing critical: cd20_ihc_status, hbsag, anti_hbc_total, lugano_stage
- Missing recommended: ldh_ratio_to_uln, fib4_index, pet_ct_date
- Unevaluated RedFlags: RF-SMZL-FRAILTY-AGE, RF-SMZL-HIGH-RISK-BIOLOGY, RF-SMZL-INFECTION-SCREENING, RF-SMZL-ORGAN-DYSFUNCTION, RF-SMZL-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 | HBsAg hbsag
| infectious_disease_hepatology | Identifies active HBV infection and prophylaxis need before anti-CD20 or other immunosuppressive therapy. | Order or document HBsAg before treatment start. | - |
| CRITICAL | Total anti-HBc anti_hbc_total
| infectious_disease_hepatology | Detects prior HBV exposure and reactivation risk. | Order or document total anti-HBc and decide prophylaxis/monitoring. | - |
| 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-HCV-RNA | HCV RNA (quantitative PCR) | infectious_disease_hepatology | no | IND-SMZL-1L-HCV-POSITIVE | Verify result, method, specimen, and report date before sign-off. Expected/constraint: detectable (positive viral load — confirms active HCV infection driving SMZL clonal proliferation; required to commit to DAA-first track) |
BIO-HCV-STATUS | HCV status (anti-HCV antibody screening) | medical_oncologist | no | IND-SMZL-1L-HCV-POSITIVE | Verify result, method, specimen, and report date before sign-off. Expected/constraint: anti-HCV-positive (categorical screen — pairs with BIO-HCV-RNA confirmation; antibody alone insufficient for treatment decision) |
Technical MDT skill metadata (3/16 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-BSH-MZL-2024: British Society for Haematology — Marginal Zone Lymphoma Guideline (2024)
- SRC-EASL-HCV-2023: EASL Clinical Practice Guidelines on Hepatitis C Virus Infection (2023)
- 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: 2026-06-11 · 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 Rituximab monotherapy (375 mg/m² weekly × 4, then maintenance) (REG-RITUXIMAB-MONO) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Sofosbuvir/Velpatasvir 12 weeks (REG-DAA-SOF-VEL) | ✓ registered | ✓ covered | ₴-? — verify pathway | AP-DAA-SOF-VEL-NSZU |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-06-11.