Pocket Oncology (Pocket Notebook Series), 1st Ed.


Andrew M. Intlekofer and Ariela Noy

Definition and Pathogenesis

• Highly aggressive B-cell NHL characterized by Myc translocation [t(8;14)(q24;q32) in 85% or variants]

• Cell of origin = germinal center or postgerminal center B cell

• DNA breaks are introduced in germinal center B cells undergoing Ig class-switching or somatic hypermutation

• Mistakes in DNA repair result in translocations that deregulate Myc expression by placing it under control of Ig gene enhancers

• Whole genome sequencing studies identified recurrent somatic mutations in TCF3 (E2A), ID3, & CCND3 (cyclinD3) (Nature 2012;490:116)


• 3 distinct clinical forms: Endemic, sporadic, immunodeficiency-associated

• Endemic: Primarily in equatorial Africa (30–50% of childhood CA), male:female, 2:1, strongly a/w EBV infxn

• Sporadic (nonendemic): US, Western Europe, 30% of pediatric lymphoma (peak age 11), <1% of adult NHL (peak age 30), male:female, 4:1

• Immunodeficiency-associated: HIV+ pts, usu CD4 count >200, incidence not impacted by HAART

Clinical Presentation

• Rapidly growing mass, doubling time <24 h, B sx (fever, sweats, wt loss)

• Typical site: Endemic Æ jaw, sporadic Æ abdomen, HIV Æ LN + extranodal

• Common involvement of extranodal sites including GI tract, mesentery, testes, ovary, kidney, breast, nasopharynx, CNS, BM, ascites, pleural effusion

Diagnostic Evaluation

• Excisional/incisional bx → histology shows sheets of medium-sized atypical lymphoid cells, extensive necrosis, frequent mitosis (Ki67 > 95%), classic “starry sky” appearance, prominent cytoplasmic vacuoles

• Immunophenotype: CD19+, CD20+, CD10+, Bcl6+, κ/λ restricted (κ > λ), surface IgM+, CD43+, CD5–, Bcl2–, TdT–, CD23–

• Karyotype, cytogenetics, FISH: Most common t(8:14) = (Myc:Ig heavy chain), less common t(2:8) = (κ light chain:Myc); t(8:22) = (Myc:λ light chain)

• Lab evaluation: CBC w/diff, CMP, phos, UA, LDH, B2M, HIV, HBV sAg/cAb

• BM bx: BM involvement in ∼70% of cases

• LP: To r/o CNS involvement, CSF cytology, & flow cytometry

• CT C/A/P w/contrast to determine extent of disease

• Echo & ECG prior to anthracycline Rx

• Fertility preservation: Sperm banking for men, women often have few options given rapid disease progression

Staging and Risk Stratification

• Ann Arbor Staging:

Stage I = single LN region or single extranodal site (IE)

Stage II = multiple LN on one side of diaphragm

Stage III = multiple LN on both sides of diaphragm

Stage IV = LN plus extranodal sites or multiple extranodal sites

A = no B sx

B = B sx (fevers, drenching sweats, wt loss >10% BW)

X = mass >10 cm

• Risk stratification:

Low risk = nl LDH & single mass <10-cm diameter

High risk = all others

Principles of Treatment

• Burkitt lymphoma is highly curable w/intensive chemotherapy, 2-y OS >70% w/modern tx regimens (see below), older adults (age >60) much lower OS

• Tx should be initiated ASAP, often w/in 48 hrs

• Tx consists of intensive regimens, usu requiring in pt monitoring

• Almost all Burkitt lymphoma regimens include CNS Ppx in the absence of overt CNS disease

→ CNS penetrating systemic drugs = high dose MTX & cytarabine

→ IT MTX & cytarabine alone = CNS Ppx

→ Known leptomeningeal disease requires intensification of IT Rx, typically delivered via Ommaya reservoir

• Virtually all pts should receive tumor lysis Ppx: IVF + allopurinol + phosphate binder ± rasburicase

• Addition of rituximab to regimens likely improves outcomes

• No role for RT (unless palliative)

Refractory Disease

• Clinical trial is preferable

• Off-protocol tx includes regimen above (not previously received) or DLBCL type salvage regimen followed by HDT w/ASCR

Supportive Care

• RBC & plt transfusions as needed

• Growth factor support w/G-CSF to prevent neutropenic fever

• Infectious Ppx for VZV & PCP/PJP

• HIV + pts: If on HAART pay attention to chemotherapy interactions