Burkitt's lymphoma- review

 Reference:

Blood Journal Feb 2021

Burkitt's is a highly aggressive B cell lymphoma.

Key points:

1. Sporadic, endemic, immunodeficiency associated.

2. Molecular feature is translocation and dysregulation of proto-oncogene- c-myc. t(2:8) or t(8:22) with heavy chain on chr 2 or light chain on chr 22 with c-myc gene on chromosome 8.

3. Endemic Burkitt's--> equatorial Africa, chronic B cell stimulation due to EBV. bm not involved but extranodal involvement of GI tract, adrenals, kidneys, and gonads, is common

4. Sporadic is more common in the western world. CNS and bm involvement common. Leptomeningeal rather than parenchymal is common.

5. HIV-associated Burkitt's is seen in patients with preserved CD4 counts, so ART has not changed the incidence. Nodal involvement is typical, but can also have CNS, GI, and bm involvement.

6. TLS is a medical emergency and can be seen even before treatment starts ie. spontaneous TLS.

evidence of spontaneous TLS or those at high risk, defined as stage III/IV disease and/or LDH ≥2 times the upper limit of normal, consensus guidelines recommend the use of rasburicase

Copyright ASH 2021

Treatment:

1. Low risk- single lesion < 10 cm, or resected abdominal disease and normal LDH-CODOX-M 3 cycles

The CODOX-M regimen is as follows:

• Cyclophosphamide 800mg/m² IV on day 1, followed by 200 mg/m² IV on days 2-5

• Doxorubicin 40 mg/m² IV on day 1

• Vincristine 1.5 mg/m² IV (no capping of dose) on days 1 and 8 (cycle 1), as well as on days 1, 8, and 15 (cycle 3)

• Methotrexate 1200 mg/m² IV over 1 hour on day 10; then 240 mg/m²/h for the next 23 hours; leucovorin rescue begins 36 hours from the start of the methotrexate infusion

• Intrathecal cytarabine 70 mg (patient older than age 3 y) on days 1 and 3

• Intrathecal methotrexate 12 mg (patient older than age 3 y) on day 15

2. All other patients i.e. high risk-CODOX-M alternating with IVAC for 2 cycles. Add Rituxan to this regimen if using.

The IVAC regimen is as follows:

• Ifosfamide 1500 mg/m² IV on days 1-5, with mesna protection

• Etoposide 60 mg/m² IV on days 1-5

• Cytarabine 2 g/m² IV every 12 hours on days 1-2

• Intrathecal methotrexate 12 mg (patient older than age 3 y) on day 5

Administration of colony-stimulating factors is usually started 24 hours after completion of chemotherapy and continues until the ANC >1000/μL.

Preferred regimen- DA-R-EPOCH

Patients were treated with 2 cycles beyond complete remission (6 to 8 total) with the exception of HIV patients who received 1 cycle beyond complete response (3 to 6 total) with 2 doses of rituximab administered with each cycle. CNS-directed therapy consisted of 8 doses of prophylactic intrathecal methotrexate with additional doses for patients with leptomeningeal disease. With long-term follow-up of >6 years, freedom from progression and OS were 95% and 100%, respectively.