Burkitt Lymphoma
Dr. Mohammed Elmourtada
8/1/2022
• I have no conflict of Interest
Objectives
• Introduction
• Diagnosis
• Presentation
• Prognostic Factors
• Treatment
Introduction
• BL is among the most aggressive of all
human malignancies, with a rapid doubling
time, acute onset, and progression of
symptoms.
Histopathology
• Diffuse growth pattern of medium-size cells
• high mitotic rate; nearly 100% of cells are Ki-67
positive
• dead cells are phagocytosed by histiocytes,
which gives a “starry- sky” appearance.
Phenotype
• The B cells are positive for CD19, CD20, BCL6, and CD10.
• BCL2 is usually negative, but rare weakly positive cases may be seen.
• Lack of terminal deoxynucleotidyl transferase is critical to rule out ALL/ lymphoblastic
lymphoma
Prepare
your mind
Proto-oncogene
• BCL-2 anti apoptotic protein ( chromosome 18)
• BCL-6 anti apoptotic protein (Chromosome 3)
• C- MYC Transcription Factor (Chromosome 8)
• Cyclin D1 transcriptional co-regulator (chromosome 11)
Enhancer
• IGH (chromosome 14)
• IGL Kapa (chromosome 2)
• IGL lambda (chromosome 22)
Cytogenetic
• (t8;14)
• t(2;8)
• t(8;22)
Types
• Endemic Form (EBV)
• Sporadic (HIV)
Presentation
• Bulky abdominal mass
• B symptoms,
• High LDH,
• Extranodal disease, including bone marrow
involvement, is common (up to 70%)
• CNS dissemination, usually in the form of
leptomeningeal involvement, may be present
at diagnosis in up to 30% of patients
Prognostic Factors
• age ≥40 years.
• LDH ≥3× upper limit of normal.
• ECOG PS ≥2.
• CNS involvement.
Treatment
• Supportive treatment
• Upfront regimen
• Salvage Treatment
Initial treatment
• Therapy for BL must be instituted quickly
because of the rapid clinical progression of
the disease
• TLS measures.
• Serious toxicity, including infectious
complications, nephrotoxicity, or
hepatotoxicity, is frequent, but treatment
mortality is low.
First line chemotherapy regimen
• CHOP
• CODOX-M and CODOX-M alternating with IVAC
• Addition of Rituximab
• HyperCVAD/methotrexate-cytarabine
regimen.
• DA-EPOCH-R
CHOP
• Multiple studies have shown that CHOP
chemotherapy is inadequate for the
treatment of BL, and intensified therapies
result in higher cure rates
CODOX-M and CODOX-M alternating with
IVAC
• Magrath et al at the National Cancer Institute
demonstrated a risk-adapted strategy that is
useful for treatment stratification in both
adults and children.
• Low-risk patients were those with a single
extra-abdominal mass or completely
resected abdominal disease and a normal
LDH, and all other patients were considered
high-risk.
• Low-risk patients received 3 cycles of CODOX-M,
and high-risk patients received CODOX-M
alternating with IVAC for a total of 4 cycles.
• All patients received intrathecal
chemoprophylaxis with each cycle, and those with
CNS disease at presentation received additional
intrathecal therapy during the first 2 cycles.
• Approximately half of the patients were adults,
and the 2-year EFS for all patients was 92%.
• Two other phase 2 studies have used the
Magrath regimen with modifications. And
both had good outcome.
Addition of Rituximab
• Because the lymphoblasts in mature B-cell NHL
exhibit strong expression of CD20, several
studies have incorporated the anti-CD20
monoclonal antibody rituximab into frontline
regimens to further improve outcome.
Evidence
• A randomized phase 3 trial of 260 adult patients with
untreated HIV-negative BL who received chemotherapy
(lymphome malin de Burkitt) with or without rituximab
(375 mg/m2) on day 1 and day 6 during the first 2
courses of chemotherapy (a total of 4 infusions).
• Three year EFS was significantly better in the rituximab
group (75% versus 62%).
• A large American-European-Australian consortium
incorporated rituximab into the treatment of high-grade,
high-risk, mature B-cell NHL such as Burkitt
lymphoma/leukemia using the lymphome malin de
Burkitt backbone that showed markedly prolonged EFS
and OS with rituximab, though at the expense of
hypogammaglobulinemia and higher infection risk.
Elderly Unfit patients
• Notably, these intensive regimens incur high rates of
toxicity and are poorly tolerated by older adults.
• The results from 12 large treatment series (10
prospective and 2 retrospective) were combined to
better determine outcome in patients with BL in
patients older than 40 years.
• In total, 470 patients were identified, 183 of whom were
older than 40 years. The median OS at 2 years with
intensive short-duration chemotherapy in older patients
was only 39% compared with 71% when all patients
were considered, suggesting an unmet need in older BL
patients.
DA-EPOCH-R
• A phase 2 study at the National Cancer Institute
evaluated DA-EPOCH-R in 30 adult patients with BL.
• The treatment was well-tolerated in older adults and
produced a 5-year EFS of more than 90%.
• This approach was then validated in a multicenter
prospective phase 2 trial of 113 adults with BL treated
at 22 centers in the United States.
• At a median follow-up of 3 years, the EFS was 85.7%;
treatment was equally effective in younger and older
patients.
• Based on these data, DA-EPOCH-R can be
considered an appropriate standard regimen for
the treatment of BL and is preferred in older
adults
Salvage Treatment
• If relapse does occur in BL, patients are
essentially not salvageable and median overall
survival is 3 to 4 months.
Reference
• ASH SAP 8th edition
Thank You
