Non-Hodgkin lymphoma

Epidemiology
60,000 cases per year; 19,000 deaths in US
Incidence is rising (Aging population?)

Risk factors
Immune deficiency
Autoimmune disease
Multiple infectious associations
 -EBV: Burkitt's, primary CNS lymphoma, T/NK cell lymphoma
 -HTLV-1: Adult T-cell leukemia and lymphoma
 -HHV-8: Kaposi's sarcoma, primary effusion lymphoma
 -HCV: splenic marginal zone lymphoma
 -H. pylori: gastric MALT lymphoma
 -Borrelia, Chlamydia, Campylobacter sp: other mucosal MALT's
Chemical exposure: herbicides, dye, nitrates, arsenic, PVC
Prior RT or chemo
Prior HD

Pathology (most common subtypes)
1) Diffuse large B-cell lymphoma: 
 -Most common (30% of cases)
 -B cell antigen positive (CD 19, 20, 45)
 -bcl-6 rearrangement

2) Follicular lymphoma
 -22% of cases
 -considered low grade/indolent
 -high rates of occult bone marrow involvement
 -B cell origin
 -t14;18 leads to transposition of bcl-2 which decreases apoptosis

3) Marginal zone/MALT
 -10% of cases
 -Most commonly involves stomach
 -trisomy 3, t11;18
 -H. pylori and Sjogren's syndrome associated

4) Peripheral T cell lymphoma
 -10%
 -Most common T cell lymphoma
 -ALK+ confers favorable prognosis

5) Small lymphocytic lymphoma
 -Thought to represent nodal focus of CLL

6) Mantle cell lymphoma
 -t11;14 amplifies bcl-1 which increases cell cycling via cyclin D1

7) Burkitt's lymphoma
 -Highly aggressive
 -Endemic subtype (Africa) is EBV+
 -t14;18 and c-myc amplification

Clinical
Most common sites: neck (70%), groin (60%), axilla (50%)
Most common extranodal sites: GI tract (25-35%), head and neck (20%)
B symptoms in 20-30%
Most patients get a bone marrow bx

International Prognostic Index (IPI) for DLBCL
Earn points for: older than 60, bad performance status (2-4), increased LDH, stage III-IV, more than 2 extranodal sites. 0-1 points has 5-yr OS 73%, 2 points 50%, 3 points 40%, 4-5 points 25%

IPI for follicular lymphoma
Risk factors: age (older than 60), stage III-IV, PS 3-4, hemoglobin under 12, increased LDH, more than 4 involved nodes. 0-1 points has 10-yr OS 70%, 2 points 50%, 3 or more points 35%.

Therapy 
Early stage, indolent histology: involved field RT alone (30-40Gy) has local control rates above 80%; however this is a systemic disease and RT is not considered curative despite the durable responses

MALT: first line therapy for gastric MALT lymphoma is triple antibiotic therapy; if this fails, 30Gy to the whole stomach provides better than 90% control and is considered curative.  For MALT's occurring outside the GI tract, 24-36Gy are typical doses.

DLBCL: subtype with best data regarding RT. However randomized data incorporating both RT and rituximab is not available.
-SWOG randomized patients with early stage DLBCL to CHOP x 8 vs. CHOP x 3 + RT.  The initial report showed an OS benefit to RT (72 vs 82% at 5 years) which disappeared with longer (10-yr) follow-up.
-ECOG randomized patients with early stage DLBCL to CHOP x 8 vs. CHOP x 8 + RT (in complete responders; all partial responders received radiation). RT improved DFS (73 vs 56% at 6 years) with a trend to improved OS.