Prospective study of Burkitt lymphoma treatment in adolescents and adults in Malawi

Abstract

Burkitt lymphoma (BL) is common in sub-Saharan Africa (SSA). In high-income countries, BL is highly curable with chemotherapy. However, there are few prospective studies from SSA describing nonpediatric BL and no regional standard of care. Thirty-five participants age 15 years or older with newly diagnosed BL were enrolled in Malawi from 2013 to 2018. Chemotherapy was administered according to institutional guidelines, with concurrent antiretroviral therapy if HIV infected. Median age was 21 years (range, 15-61) and 15 participants (43%) were HIV infected. Twenty-seven participants (77%) had stage III to IV disease, and 19 (54%) had Eastern Cooperative Oncology Group performance status >1. Among HIV-infected participants, median CD4 count was 130 (range, 29-605) and 10 (67%) had suppressed HIV viral load. Four participants (11%) died before receiving chemotherapy. First-line chemotherapy consisted of: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 22 [71%]); infusional etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin (n = 4 [13%]); high-dose methotrexate-based chemotherapy (n = 4 [13%]); and rituximab plus CHOP (n = 1 [3%]). Among 28 evaluable participants, 14 (50%) achieved a complete response. Median overall survival (OS) was 7 months; 1-year OS was 40% (95% confidence interval [CI], 24%-56%). Sixteen (73%) of 22 deaths were a result of disease progression. Compared with CHOP, more intensive chemotherapy was associated with decreased mortality (hazard ratio, 0.24; 95% CI, 0.05-1.02; P = .05). This is among the best characterized prospective cohorts of nonpediatric BL in SSA. Most deaths resulted from progressive BL. Patients who received more intensive therapy seemed to have better outcomes. Defining optimal approaches is an urgent priority in SSA.

Graphical abstract

Figure 1.

Representative pathology from a patient with BL. Hematoxylin and eosin stain demonstrates typical starry-sky appearance with a diffuse infiltrate of medium-sized lymphocytes and tingible-body macrophages (A), CD20 stains the malignant cells (B), CD10 stains the malignant cells (C), BCL2 is negative in the malignant cells and stains positive in background T lymphocytes (D), TdT is negative (E), and Ki67 is positive (F) in >95% of malignant cells. Magnification ×40 for all images.

Figure 2.

Flowchart of first-line chemotherapy and outcomes among newly diagnosed patients with BL in Lilongwe, Malawi.

Figure 3.

Kaplan-Meier curves for OS. OS curves shown for entire cohort (with 95% CI bands) (A), by HIV status (B), by aaIPI (C), and by treatment (CHOP vs more intensive regimens) (D).