Revisiting predictors of high-dose methotrexate related severe nephrotoxicity in children with acute lymphoblastic leukemia

Abstract

Introduction

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and high-dose methotrexate (HDMTX) is a key chemotherapeutic agent. HDMTX can cause nephrotoxicity. This study aimed to identify prognostic indicators of HDMTX-related severe nephrotoxicity in children with ALL.

Methods

A retrospective review of children with ALL treated at Chiang Mai University Hospital (2016–2020) was conducted. Demographic, clinical, and treatment-related factors associated with HDMTX-related severe nephrotoxicity were analyzed using multivariable multilevel logistic regression, reported as adjusted odds ratio (aOR).

Results

A total of 61 children with ALL underwent 243 HDMTX infusion cycles. HDMTX-related severe nephrotoxicity occurred in 37.7% (23/61) of patients and 12.3% (30/243) of infusion cycles. No significant differences in baseline characteristics were observed. Concurrent amikacin use was an independent risk factor (aOR = 17.693 [1.613–194.032] P = 0.019), while higher baseline urine pH was protective (aOR = 0.190 [0.082–0.440] P < 0.001). A baseline urine pH < 7.0 was identified as the optimal cutoff for predicting HDMTX-related severe nephrotoxicity (area under the ROC curve = 0.72 [0.63–0.81]). All nephrotoxic events resolved completely.

Conclusions

Concurrent amikacin use and low baseline urine pH are significant predictors of HDMTX-related severe nephrotoxicity in children with ALL. Identification of these factors is crucial for preventing nephrotoxicity.