ASSESSMENT OF THE TOXICITY OF HIGH-DOSE METHOTREXATE ACCORDING TO THE "M" PROTOCOL IN THE TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN: A RETROSPECTIVE ANALYSIS

A. Bazarbayeva, Lyazat Manzhuova, Г Т Мырзабекова, I. Dzhaksybayeva, A. Turginbayeva, I. Ramazanova, A. Toqtarkyzy

2026

Full text Open access: Hybrid Metadata (CSL-JSON)
DOI 10.52532/3135-3940-2026-2-793
Data confidence 70 medium
How this score is calculated

It is built from checkable properties of the record itself: whether the article has a DOI, how many independent sources confirmed its data, whether the required fields are filled in, and how recent the latest confirmation is. Disagreement between sources and a missing identifier lower it. A value of 80 or above means the record was published without further checking; 60 to 79 means it is published at reduced confidence, with a manual check advisable. A record verified by an editor by hand is never pushed below 90 by a recalculation. This scores our data about the article, not the article itself.

Abstract

Relevance: Acute lymphoblastic leukemia (ALL) is the most common malignant disorder of the hematopoietic system in children. High-dose methotrexate is widely used in modern treatment regimens for ALL, including Protocol M. However, its administration may be associated with toxic reactions affecting various organs and systems.The study aimed to explore the frequency, nature, and severity of toxic manifestations associated with the use of high-dose methotrexate according to Protocol M in children with ALL.Materials and Methods: A retrospective analysis of medical records was performed for 108 children with newly diagnosed ALL who received treatment at the Scientific Center of Pediatrics and Pediatric Surgery (Almaty, Kazakhstan) from January 2021 to December 2024. All patients were treated according to the AIEOP-BFM ALL 2009 protocol. After protocol I, all patients in remission from standard- and medium-risk groups were transferred to treatment according to protocol M, which included 4 alternating cycles of a 24-hour intravenous infusion of high-dose methotrexate (HD-MTX) at 5 g/m². A total of 413 HD-MTX courses were analyzed. Adverse events were assessed according to the criteria of the United States National Cancer Institute.Results: The most common toxic manifestation was gastrointestinal syndrome (n = 331, 80.1%). Dermatological complications were registered in 277 cases (67.1%), infectious complications in 213 cases (51.6%), and signs of hepatotoxicity in 188 cases (45.5%). In children older than 5 years, hematological toxicity was observed in 215 of 319 courses, accounting for 67.4%; severe grade III-IV toxicity manifestations were registered in 67 cases (21%). Metabolic disorders were identified in 144 cases (34.8%), nephrotoxicity in 32 cases (7.9%), cardiotoxicity in 41 cases (9.9%), and neurotoxicity in 16 cases (3.9%). Kidney, heart, and nervous system involvement corresponded to grade III toxicity in most cases.Conclusion: The use of high-dose methotrexate according to Protocol M in children with ALL is most often accompanied by transient toxic reactions. Gastrointestinal, dermatological, hematological, and infectious complications are most common. To reduce the risk of adverse events, it is necessary to strictly follow supportive care measures and timely adjust the leucovorin dose.