Therapy of Advanced-stage Mature B-cell Lymphoma and Leukemia in Children and Adolescents With Rituximab and Reduced Intensity Induction Chemotherapy (B-NHL 2004M Protocol)

Abstract

Pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs) are highly aggressive malignant tumors that are curable with chemotherapy (ChT). High-dose methotrexate (MTX) is considered indispensable for successful treatment, but this therapy frequently induces severe mucositis and infectious complications, especially in induction, which can cause treatment failure. A prospective multicenter trial of combined immunochemotherapy for advanced-stage B-NHL with rituximab and the modified NHL-BFM-90 protocol was conducted. The major differences from the original protocol were a decrease in the dose of MTX from 5000 to 1000 mg/m/24 h in the first 2 ChT blocks and the addition of rituximab at 375 mg/m to each of the first 4 blocks of ChT. Eighty-three newly diagnosed patients with a median age of 8.84 years with Burkitt lymphoma/leukemia and diffuse large B-cell lymphomas stage III to IV were included. Four patients died during induction ChT due to tumor lysis syndrome and infection. Two additional patients died subsequently due to tumor resistance. Complete remission was achieved in 77 (92.8%) patients; 2 patients relapsed at 1 and 3 months, and 2 developed secondary malignancies at 1 and 6.5 years, respectively, after the completion of therapy. The overall survival probability was 82%±8% with a median follow-up of 65.2 months. Combined therapy with rituximab and intensive ChT with a reduced MTX dose of 1 g/m in the 2 induction courses was feasible and produced high cure rates in patients with pediatric advanced-stage mature B-NHL.

Prospective Study of a Cohort of Russian Nijmegen Breakage Syndrome Patients Demonstrating Predictive Value of Low Kappa-Deleting Recombination Excision Circle (KREC) Numbers and Beneficial Effect of Hematopoietic Stem Cell Transplantation (HSCT)

“…Patients with mature B-cell lymphomas were treated according to modified BFM-NHL 2010 core protocol chemotherapy and rituximab (13), peripheral T-cell lymphomas were treated according to individual schemes, leukemias were treated according to approved MB-ALL2008 or ALL-BFM-2005 protocols. A reduction of doses was implemented in seven patients, the majority (13 patients) received non-reduced chemotherapy with no significant toxicity.…”

Outcome of pediatric non‐Hodgkin lymphoma in Central America: A report of the Association of Pediatric Hematology Oncology of Central America (AHOPCA)

“…This approach could avoid the need to increase the dose intensity of drugs with multiorgan toxicity. A prospective study in Russian children showed that using rituximab in early therapy of mature B‐cell neoplasms resulted in a 5% induction death rate and an overall survival of 82% . However, the relatively high cost of rituximab may restrict its use in limited‐resource settings.…”

Trends in survival of patients with stage I/II Burkitt lymphoma in the United States: A SEER database analysis

“…There is a small subset of BL presents in stage I and II (limited stage) and this small population has a better outcome than those with advanced stage . The outcome of patients with advanced stage has improved in the recent era owing to the use of more intense chemotherapy regimens, the availability of rituximab, the application of antiretroviral therapy (ART), and improvements in supportive care . However, it is unclear whether the recent changes in management modalities have affected the survival of limited‐stage BL patients who already had excellent cure rates.…”