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Intensive, very short-term chemotherapy for advanced Burkitt's lymphoma in children
Filippo Spreafico1, Maura Massimino, Roberto Luksch
1Department of Pediatric Oncology, Istituto Nazionale Tumori, Milan, Italy. f.spreafico@istitutotumori.mi.it
Insights
Intensified chemotherapy for advanced Burkitt's lymphoma (BL) significantly improved event-free survival (EFS) in children. This 45-day intensive program is the shortest schedule for disseminated BL, overcoming risk factors like bone marrow and CNS involvement.
Area of Science:
- Pediatric Oncology
- Hematologic Malignancies
- Clinical Trials
Background:
- Burkitt's lymphoma (BL) in advanced stages (III-IV) previously had a low event-free survival (EFS) of 63% before 1986.
- Intensification of chemotherapy and supportive care strategies were explored to improve outcomes.
Purpose of the Study:
- To enhance the event-free survival (EFS) for children diagnosed with advanced stage III to IV Burkitt's lymphoma (BL).
Main Methods:
- Sixty children with advanced BL were enrolled in sequential studies from 1987 to 2001.
- Patients received intensive 45-day chemotherapy regimens (IA, IB, or II) involving multiple agents, including high-dose methotrexate and cytarabine, with or without etoposide and ifosfamide.
- Stratification was based on bone marrow (BM) or central nervous system (CNS) involvement in earlier phases, with later protocols treating all patients similarly.
Main Results:
- The 5-year EFS and disease-free survival rates were 81% ± 5% and 87% ± 5% for 59 assessable patients.
- Regimen II showed promising results with 89% ± 6% EFS and disease-free survival.
- Treatment-related complications led to five deaths, none in the Regimen II group, while initial treatment failure or relapse caused six deaths.
Conclusions:
- A 45-day intensive chemotherapy program represents the shortest schedule for disseminated BL.
- This intensive regimen effectively overcomes previously identified risk factors, including bone marrow and CNS infiltration.
- The intensified approach significantly improves survival outcomes for pediatric patients with advanced Burkitt's lymphoma.
Purpose:
To improve the 63% event-free survival (EFS) achieved before 1986 in Murphy's stage III to IV Burkitt's lymphoma (BL), both chemotherapy and supportive care were intensified.
Patients And Methods:
From May 1987 to February 2001, 60 children, median age 9 years (range, 2.1 to 17 years), with advanced BL were enrolled onto two sequential institutional studies. From 1987 to 1992, 30 patients were stratified according to the absence (regimen IA, n = 19) or presence (regimen IB, n = 11) of bone marrow (BM) or CNS involvement. After 5-week cytoreductive chemotherapy consisting of vincristine, cyclophosphamide, doxorubicin, high-dose (HD) methotrexate (MTX), and intrathecal MTX or cytarabine, HD cytarabine and cisplatin were provided as a 4-day continuous infusion. Regimen IB was intensified by adding etoposide and HD ifosfamide and escalating MTX doses. Since 1992, regardless of BM or CNS status, 30 patients have been placed on regimen II, which is identical to IB but without ifosfamide. The scheduled duration of regimen II was 45 days.
Results:
EFS and disease-free survival at 5 years are 81% +/- 5% and 87% +/- 5%, respectively, for 59 assessable patients (73% +/- 8% and 85% +/- 7% for regimen IA + IB, 89% +/- 6%, EFS and disease-free survival, for regimen II; median follow-up, 6.7 years; range, 0.6 to 13.5 years). Six patients, two of whom were receiving regimen II, died as a result of initial treatment failure or relapse, and five patients, none receiving regimen II, died as a result of treatment-related complications.
Conclusion:
This 45-day intensive chemotherapy program is the shortest schedule for disseminated BL and overcomes previously recognized risk factors such as BM and CNS infiltration.