Experience with high dose methotrexate therapy in childhood acute lymphoblastic leukemia in a tertiary care cancer centre of a developing country

Abstract

Intensification of systemic chemotherapy with inclusion of high dose methotrexate (HDMTX) has helped omit cranial irradiation from standard risk acute lymphoblastic leukemia (ALL) protocols, thereby eliminating the adverse side effects associated with its use. Administration of HDMTX needs meticulous monitoring. Limitations in the availability of trained staff and adequate infrastructure often pose problems in the developing world. The aim of this study was (1) to treat childhood ALL with a protocol that would have reduced use of cranial irradiation and containing infusions of high-dose methotrexate HDMTX (5 g/m(2)) without compromising on survival, and (2) evaluate the experience with HDMTX in a tertiary care cancer centre in a developing country. A retrospective chart review was done of 41 consecutive children with a confirmed diagnosis of ALL who had received at least one cycle of HDMTX as part of their consolidation treatment with regard to the patient demographic profile, details of HDMTX infusion and leucovorin rescue, toxicity, additional hospitalization, delay in next cycle of chemotherapy and survival. The clinically most significant toxicities observed were mucositis 39% (58/149) and fever 28% (42/149) together leading to additional hospital stay in 7% (11/149) cycles and neutropenia grade 3 or more in 24.8% (34/137) contributing to delay in next cycle of chemotherapy in 15% (23/149) cycles. With this strategy, it was possible to omit or reduce the dose of cranial irradiation while maintaining survival outcomes. The administration of HDMTX therapy was found to be feasible and safe with the precautions described.