Non-Hodgkin Lymphoma March 13, 2013 Suzanne R. Fanning, DO Greenville Health System

Myelopoesis

NHL Heterogenous group of neoplastic diseases derived of monoclonal lymphocytes. B or T cell in origin Indolent vs. aggressive Characterized by morphology, immunophenotype, and genetic mutations

Incidence vs. mortality

NHL Indolent: slowing progressive lymphadenopathy cytopenias hepato/splenomegaly Aggressive: rapidly growing mass systemic B symptoms elevated LDH/uric acid

Pediatric NHL

5 th most common malignancy <15yr 7% of pediatric cancers 800 cases/yr in the US Median age: 10 >90% stage I/II Good prognosis (OS>80%)

Diagnosis Excisional biopsy (not FNA) Morphology Immunophenotype Genetic studies: conventional karyotype FISH PCR (immunoglobulin gene rearrangement)

Histology Nodular Tends to be slow growing Diffuse Aggressive Cutaneous

Histology

Immunostains

DLBCL - phenotype

Cutaneous B cell NHL

Cutaneous T cell NHL

Risk factors Family history Prior hematologic malignancy Prior chemotherapy and/or radiation Immunosuppressive medications History of organ transplant Pesticides/Agent orange Infections

Hepatitis B or C HIV HTLV-1 Super rare EBV Chlamydia pisittaci Causes an ocular lymphoma  tx = doxycycline Borrelia burgdorefi Rare

Risk factors Autoimmune disorders Immunodeficiency disorders Mixed cryoglobulinemia Rare Multicentric Castleman’s disease Infammatory GI disorders: chron’s, celiac, H. pylori- associated gastritis

Presentation Painless lymphadenopathy Fatigue B symptoms: fever (>100.4) night sweats weight loss (>10%/6 mo)

Presentation - less common Rash Pruritus Malaise Ascites Effusion Pleural and pericardial

Extranodal disease 50% of cases have extranodal involvement 10-35% present as primary extranodal GI - most common Primary CNS NHL - rare

Extranodal sites

Labs CBC CMP LDH Uric acid Serum protein electrophoresis – assessment for monoclonal protein

Staging studies CT C/A/P (+/- neck) PET/CT scan – especially if aggressive disease Bone marrow biopsy morphology cytogenetics/FISH

Staging – Ann Arbor I: one lymph node group II: 2 LN groups on same side of diaphragm III: LN involvement on both sides of diaphragm IV: as above with bone marrow involvement A or B: w/ or w/o B symptoms E: extranodal

Lymphatic system

Internation Prognostic Index (IPI)

FLIPI Similar to IPI Appropriate for follicular NHL age stage LDH hemoglobin # of LN groups instead of extranodal groups involved

Treatment – Indolent NHL Asymptomatic: surveillance Symptomatic: Early stage: radiation single-agent rituxan Advanced stage: multi-agent chemotherapy

Cell cycle

Chemotherapy effects on cell cycle

Treatment - Indolent Chemotherapy regimens for advanced stage: R-CVP – Rituxan, cytoxan, vincristine, prednisone BR – bendamustine, Rituxan FCR – fludarabine, cytoxan, Rituxan

Treatment - DLBCL Early stage (I-II): R-CHOP x 3 Involved field radiation

Treatment - DLBCL Advance stage (III/IV): R-CHOP x 6-8 cycles

R-CHOP Rituxan Cytoxan Adriamycin Vicristine Prednisone

Rituximab

Rituximab/CD 20 target

10-year survival

Gene expression profile

Relapsed NHL Alternate chemotherapy regimens Radiation to symptomatic regions ASCT – autologous stem cell transplant Allogeneic transplant Palliative/symptomatic care

Thank you!