A single assessment of methotrexate levels at 42 hours permits safe administration and early discharge in children with lymphoblastic lymphoma and leukemia receiving high-dose methotrexate

Pediatr Hematol Oncol. 2021 Aug;38(5):434-443. doi: 10.1080/08880018.2020.1863535. Epub 2021 Mar 25.

Abstract

High-dose methotrexate (HDMTX) is an important component of treatment in pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Optimal rescue therapy is essential for the safe administration of HDMTX. A cost-effective strategy that does not compromise safety is necessary for low- and middle-income countries. Consecutive admissions for HDMTX in children with ALL and LL over 12 months were analyzed. The dose of HDMTX was 3 g/m2 in B-ALL and B-LL and 5 g/m2 in T-ALL and T-LL. A methotrexate level was measured at 42 hours of starting HDMTX infusion (T42-MTX). Three doses of folinic acid at T42, T48, and T54 and alkalinized hydration till T54 were administered if T42-MTX <1 µM. A total of 282 cycles of HDMTX that were administered in 71 patients were analyzed. T42-MTX was <1 µM in 266 (94.3%) cycles. T42-MTX was ≥1 µM in 12% and 3% of cycles of HDMTX administered at a dose of 5 g/m2 and 3 g/m2, respectively (p = .074). The median duration of hospitalization for HDM was three days and did not differ with the dose of HDMTX administered (p = .427). Mucositis, delayed recovery of blood counts, and hospitalization for reversible toxicity occurred after 21 (7.4%), 28 (9.9%), and 19 (6.7%) cycles of HDMTX, respectively. Mucositis was greater following the administration of 5 g/m2 of HDMTX. A single T42-MTX measurement permits the safe administration of HDMTX and an expedited discharge from the hospital within three days in more than 90% of children with ALL/LL.

Keywords: Chemotherapy; LMIC; intravenous methotrexate; nephrotoxicity; resource limited.

MeSH terms

  • Adolescent
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / blood
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Monitoring
  • Female
  • Humans
  • Infant
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Methotrexate / blood
  • Methotrexate / therapeutic use*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Retrospective Studies

Substances

  • Antimetabolites, Antineoplastic
  • Methotrexate