Advanced Burkitt Lymphoma in Sub-Saharan Africa Pediatric Units: Results of the Third Prospective Multicenter Study of the Groupe Franco-Africain d’Oncologie Pédiatrique

Abstract

PURPOSETo evaluate the results of an intensive polychemotherapy regimen for Burkitt lymphoma (BL) in sub-Saharan African pediatric centers.PATIENTS AND METHODSChildren with advanced-stage BL (stages II bulky, III, and IV) treated with the GFAOP–Lymphomes Malins B (GFALMB) 2009 protocol in 7 centers between April 2009 and September 2015 were prospectively registered. Treatment regimen contained a prephase with cyclophosphamide followed by 2 induction courses (cyclophosphamide, vincristine, prednisone, high-dose methotrexate [HDMTX]), 2 consolidation courses (cytarabine, HDMTX), and a maintenance phase only for stage IV. HDMTX was given at the dose of 3 g/m2.RESULTSFour hundred patients were analyzed: 7% had stage II bulky, 76% stage III, and 17% stage IV disease. Median age was 7.3 years, and sex ratio was 1.9:1 (male:female). A total of 221 patients received the whole protocol treatment and 195 achieved complete remission (CR), 11 of them after a second-line treatment. Treatment abandonment rate was 22%. One hundred twenty-five patients died, of whom 49 deaths were related to treatment toxicity. A total of 275 patients are alive, including 25 despite treatment abandonment, but only 110 are known to be in CR with a follow-up > 1 year, indicating a high rate of loss to follow-up. Twelve-month overall survival (OS) was 60% (95% CI, 54% to 66%) and 63%, 60%, and 31%, respectively, for stage II bulky, III, and IV. Patients with stage III disease who started second induction course within 34 days had OS of 76%, versus 57% (P = .0062) beyond 34 days.CONCLUSIONThe GFA-LMB2009 protocol improved patients’ survival. Early dose intensity of treatment is a strong prognostic factor. Improving supportive care and decreasing loss to follow-up are crucial.

Immune Landscape in Burkitt Lymphoma reveals M2-macrophage polarization and Correlation between PD-L1 expression and Non-Canonical EBV latency program

“…5 Furthermore, in equatorial Africa, where BL is the most common childhood cancer, the prognosis of BL is still poor because the intensive therapeutic regimens often result in a severe neutropenia, with fatal consequences in resource poor settings. [6][7][8][9][10] Shortcomings of current BL therapies make the exploration of new therapeutic avenues a substantial and reasonable aim. 7 Therefore, a proper characterization of the TME in BL might be helpful to identify alternative therapeutic targets.…”

Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program

“…Unfortunately, these burdensome treatments are not as effective in elderly and immunocompromised patients [5]. Furthermore, in equatorial Africa, where BL is the most common childhood cancer, the prognosis of BL is still poor because the intensive therapeutic regimens often result in a severe neutropenia, with fatal consequences in resource poor settings [6][7][8][9][10]. Shortcomings of current BL therapies make the exploration of new therapeutic avenues a substantial and reasonable aim [7].…”

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

“…26,38,40,41,[48][49][50] This is particularly relevant because numerous studies in SSA have demonstrated that abdominal mass has become at least as common as jaw mass as a presenting feature of endemic BL (Figure 1). 17,20,51,52 A recent clinical quality improvement project at the Uganda Cancer Institute is emblematic of the lack of progress in improving outcomes: over a 5-year period (2012-2017), 180 children with pathology-confirmed diagnoses of BL were treated with COM, with resources dedicated to ensuring accurate diagnosis, chemotherapy availability, and treatment compliance. 44 Despite mitigating limitations of access to care, the 4-year OS was 44%, 44 similar to results from clinical trials at the same center from the 1970s.…”

“…They were able to reproduce the superior outcomes seen in the earlier experience with a 1-year OS of 60% for patients with advanced-stage disease and a TRM of 12%. 51 Using a modified LMB regimen, they continued to deliver the first 2 induction cycles with cyclophosphamide, vincristine, prednisone, and hdMTX for 2 cycles, followed by hdMTX plus mini-cytarabine (500 mg/m 2 per cycle) for 2 cycles, including 3000 mg/m 2 of MTX over 3 hours. 51 The progress made by GFAOP highlights the necessity for enhanced supportive care along with intensified MTX.…”