High-dose methotrexate in the treatment of acute lymphoblastic leukemia: Toxicity profile and comparison of tolerability betwen two dosage schedules.

Abstract

9573 Background: Aims: To study the toxicity profile of high-dose methotrexate in treatment of acute lymphoblastic leukemia. To compare between tolerability of 3 gm/ m2 and 5 gm/m2 of high-dose methotrexate (HDMTX). Methods: 60 acute lymphoblastic leukemia patients undergoing BFM 86 protocol treatment at Cancer Institute, Chennai, without any renal dysfunction or neurological disorder. 30 patients each were administered four cycles of consolidation chemotherapy with 3 gm/m2 and 5 gm/m2 HDMTX respectively once in 14 days. Statistical methods used included Student t test, Chi square test and Fisher exact test. Results: See Table. Comparison of toxicities between two dosages of 3gm/ m2 and 5 gm/ m2: There were no statistically significant differences between various parameters like average number of days to complete the protocol, rise in serum creatinine, Grade of mucositis and LFT abnormalities between the two groups. Incidence of febrile neutropenia, use of antibiotics and number of days 6MP was given was also similar. Conclusions: 1) Adequate hydration, alkalanization, and leucovorin rescue with close monitoring of serum creatinine as well as methotrexate levels are essential to prevent life threatening toxicities. 2) HDMTX could be safely administered across all age groups in the study population. 3) Myelosuppression and febrile neutropenia resulted in treatment delays. 4) Cumulative toxicity of HDMTX with repeated infusions was not noted. 5) There was no significant difference in tolerability between 3 gm/m2 and 5 gm/m2 of HDMTX. Toxicities associated with HDMTX (including both groups) Toxicity Number (out of 240) Percentage Doubling of creatinine 2 0.9% 50% rise in creatinine at 48 hours post HDMTX 9 3.75% Mucositis grade 2 or more 11 4.5% Transaminitis grade 2 or more 18 7.5% Neutropenia grade 2 or more 70 29% Febrile neutropenia 59 24.5% Thrombocytopenia grade 2 or more 16 6.6% Mean number of days delayed 5.6 N.A. No significant financial relationships to disclose.