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The definitive treatment of children with acute leukemia
Insights
Current chemotherapy improves outcomes for children with acute lymphocytic leukemia (ALL). Standard induction with prednisone and vincristine achieves remission in 90% of patients, but optimal central nervous system and maintenance therapies require further study.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Pharmacology
Background:
- Acute lymphocytic leukemia (ALL) in children under 16 has seen improved prognoses with current therapies.
- Standard induction chemotherapy, including prednisone and vincristine, achieves high remission rates.
Purpose of the Study:
- To review current therapeutic strategies for childhood acute lymphocytic leukemia.
- To identify areas where further research is needed to optimize treatment protocols and minimize toxicity.
Main Methods:
- Review of current treatment protocols for pediatric acute lymphocytic leukemia.
- Analysis of established and potential therapeutic agents and modalities.
- Discussion of treatment-related complications and long-term outcomes.
Main Results:
- Prednisone and vincristine combination achieves hematologic remission in approximately 90% of patients.
- Efficacy of additional agents (L-asparaginase, daunomycin), consolidation, or readministration of induction drugs is not established.
- Central nervous system prophylaxis is crucial, but optimal methods and their associated toxicity (encephalopathy) are not defined.
- Maintenance chemotherapy, often for 3 years, requires further investigation regarding optimal duration due to toxicity concerns.
Conclusions:
- Intensive chemotherapy and central nervous system prophylaxis have improved outcomes for childhood ALL.
- Significant treatment failures necessitate the development of a standardized, optimal therapeutic approach.
- Further research is needed to establish the most effective and least toxic central nervous system and maintenance therapies.
Abstract:
Current therapy has resulted in improved prognosis in previously untreated children with acute lymphocytic leukemia less than 16 years of age. The induction phase of chemotherapy should include the use of at least prednisone and vincristine. This combination should result in a hematologic remission in about 90 per cent of the patients. The efficacy of the addition of either L-asparaginase or daunomycin, the consolidation phase or the periodic readministration of induction drugs has not been established. Specific central nervous system treatment, early in the course of therapy, is an integral component of recently reported effective protocols. Several modalities of prophalytic central nervous system therapy have been utilized. These include cranial irradiation plus intrathecal methotrexate, craniospinal irradiation and intrathecal methotrexate alone. An encephalopathy syndrome has been reported as a complication in 10 to 66 per cent of these patients. The most effective form of central nervous system therapy, associated with the least toxicity, has not been established. Maintenance chemotherapy should include a combination of two or more drugs. Complications are numerous, and include hematopoietic depression, immunosuppression, overwhelming infections, and, possibly, the development of secondary primary cancers. In the most successful protocols maintenance chemotherapy has been administered for 3 years. Because of the potential significant toxicity there is a need to define the optimal duration of maintenance therapy. Psychological complications developing in a patient with a disease now considered a potential long term chronic illness, rather than a disease once considered universally fatal, are also discussed. The possibility of an immunologic deficiency allowing for the initial development of acute lymphocytic leukemia and the role of immunotherapy are presented. While the use of intensive combination chemotherapy and specific central nervous system prophylactic therapy have resulted in an improved prognosis in childhood acute lymphocytic leukemia, because of a significant incidence of failures, a standardized single form of therapy has not been established.