Five decades of low intensity and low survival: adapting intensified regimens to cure pediatric Burkitt lymphoma in Africa

Abstract

Long-term cure of childhood Burkitt lymphoma (BL) in sub-Saharan Africa after treatment with single-agent cyclophosphamide has been documented for more than half of a century. Contemporary cure rates for the highest-risk patients with BL in high-income countries exceed 90% using intensive multiagent chemotherapy. By contrast, the majority of African children with BL still die. Data spanning 5 decades in Africa have repeatedly shown that the children most likely to achieve cure with limited cyclophosphamide regimens are those with lower-stage disease isolated to the jaw. Attempts to intensify the cyclophosphamide monotherapy backbone with the addition of vincristine, low-dose methotrexate, prednisone, doxorubicin, and/or low-dose cytarabine have not yielded significant improvement. High-dose methotrexate is a critical component in the treatment of childhood BL worldwide. Although initial efforts in Africa to incorporate high-dose methotrexate resulted in high treatment-related mortality, more recent collaborative experiences from North and West Africa, as well as Central America, demonstrate that it can be administered safely and effectively, despite limitations in supportive care resources. Recognizing the unacceptable disparity in curative outcomes for BL between the United States/Europe and equatorial Africa, there is a critical need to safely adapt contemporary treatment regimens to optimize curative outcomes amid the resource limitations in regions where BL is endemic. Here, we critically review reports of BL treatment outcomes from low- and middle-income countries, in addition to data from high-income countries that predated modern intensified regimens, to identify potential strategies to improve the therapeutic approach for children suffering from BL in sub-Saharan Africa.

Epstein-Barr Virus Induced Cytidine Metabolism Roles in Transformed B-Cell Growth and Survival

“…Nonetheless, EBV is associated with 200,000 human cancers per year, including Burkitt lymphoma, posttransplant lymphoproliferative diseases, Hodgkin lymphoma, and gastric and nasopharyngeal carcinoma ( 1 , 2 ). Endemic Burkitt lymphoma caused by EBV remains the most common childhood cancer in sub-Saharan Africa ( 3 – 5 ).…”

Plasma EBV DNA: A Promising Diagnostic Marker for Endemic Burkitt Lymphoma

“…The report from Hong Kong using plasma EBV DNA screening for nasopharyngeal carcinoma suggested that screening of high risk populations facilitated earlier diagnosis and resulted in increased survival rates. In this regard, we note that the cure rate for pediatric BL in high resource settings with chemotherapy is >90% ( 20 , 21 ). However, in limited resource settings, the cure rate for endemic BL is much lower—44% in a recent report from Uganda ( 22 ).…”

Safety Analysis of High-Dose Methotrexate in Pediatric Non-Hodgkin Lymphomas

“…Most children diagnosed with non-Hodgkin lymphoma (NHL) in high-income countries are expected to achieve long-term survival; however, children in lower income countries are diagnosed with NHL at a disproportionally higher rate and do not experience the same chance for cure. [1][2][3][4][5][6][7][8][9][10] This disparity is related to many factors, including late disease detection and challenges in delivering high-intensity treatment, such as methotrexate. [3] High-dose methotrexate (HD-MTX; 1-8 g/m 2 ) is an essential component of pediatric mature B-cell and T-cell NHL treatment.…”

“…[1][2][3][4][5][6][7][8][9][10] This disparity is related to many factors, including late disease detection and challenges in delivering high-intensity treatment, such as methotrexate. [3] High-dose methotrexate (HD-MTX; 1-8 g/m 2 ) is an essential component of pediatric mature B-cell and T-cell NHL treatment. [11] The use of HD-MTX in lower income countries has been challenging due to treatment-related mortality at doses of 1-2 g/m 2 , yet even higher doses are needed to adequately treat NHL.…”