Pediatric mature B-cell non Hodgkin lymphoma treatment with LMB-96 protocol. The Children Cancer Hospital Egypt experience

Abstract

Purpose: Burkitt lymphoma (BL) is a highly aggressive mature B-cell non-Hodgkin lymphoma (NHL) and is the fastest growing human tumor. The outcome of childhood NHL has improved steadily over the past decades through the use of intensive sequential multi-agent chemotherapy regimens. Methods: A retrospective study having all patients 18 years old or younger diagnosed with mature B cell NHL and treated at Children Cancer Hospital Egypt (CCHE). All children were treated according to the modified (LMB 96) protocol during the period between July 2007 and December 2012. Patients were followed up till June 2013. Results: Three hundred and seventy-seven patients were diagnosed with mature B cell NHL and received the LMB96 treatment protocol. The majorities were males (76.4%) with a median age of 5.3 years, and ranged from 0.1-18.0 years. The median follow-up period was 28.2 months (range 0.9-72 months). Burkitt lymphoma was the most predominant pathologic subtype (79.6%, n = 300), and abdominal mass as a primary site was the most common presentation (71.3%). Twenty seven patients (7.2%) were treated as group A, 268 (71.0%) as group B, and 82 (21.8%) patients as high risk group C. Seventy-one (18.8%) patients suffered adverse events. Major adverse events were early deaths in 17 patients (4.5%), death during induction chemotherapy seen in 18 patients (4.7%), and during maintenance therapy in 7 patients (1.8%), tumor progression in 19 patients (5.0%), and relapse in 10 patients (3.7%). Sixty-three patients (16.7%) died during the study period. The main causes of death were tumor lysis syndrome (TLS) in 25.3%, and severe sepsis during chemotherapy in 41.3% of the patients. The 3 years OS and EFS were 83.3% and 80.4% respectively for the whole groups of patients. OS and EFS were 100% for group A, and 87.5%±3.9% and 85.9±4.3% for group B. For group C BM + /CNS - patients, OS was 55.62%±15.8%, and EFS of 53.8%±15.6%. For BM + /CNS + patients, OS and EFS were 63.2%±21.76% and 57.9%±22.1% respectively. BM - /CNS + patients had OS 72.4%±18.8% and EFS 67.6%±19.7% at 36 months. Conclusion: TLS and chemotherapy related toxicity remains a major challenge affecting the outcome of pediatric mature B cell NHL. We identified bone marrow involvement as a risk factor affecting treatment outcome. Aggressive supportive care measures are mandatory to avoid unacceptable high toxicity related mortality.