Outpatient administration of high-dose methotrexate in adults without drug monitoring - a case-control study of risk factors for acute kidney injury

Camila Alves; Juliana Pereira; Eduardo M Rego; Vanderson Rocha; Wellington F Silva

doi:10.1016/j.htct.2023.10.005

Outpatient administration of high-dose methotrexate in adults without drug monitoring - a case-control study of risk factors for acute kidney injury

Hematol Transfus Cell Ther. 2023 Dec 19:S2531-1379(23)02599-3. doi: 10.1016/j.htct.2023.10.005. Online ahead of print.

Authors

Camila Alves¹, Juliana Pereira², Eduardo M Rego², Vanderson Rocha², Wellington F Silva³

Affiliations

¹ Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil.
² Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Division of Hematology and Cell Therapy, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil; Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil.
³ Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology (LIM-31), Division of Hematology and Cell Therapy, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil; Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-000, Brazil. Electronic address: wellington.fernandes@hc.fm.usp.br.

PMID: 38233304
DOI: 10.1016/j.htct.2023.10.005

Abstract

Introduction: High-dose methotrexate (HDMTX) is an essential part of chemotherapy regimens for hematologic neoplasms. The incidence of acute kidney injury (AKI) after HDMTX in unmonitored outpatient infusion had not been reported in adults yet. In this study, we evaluated toxicity data after outpatient administration of HDMTX without drug monitoring.

Methods: Patients 16 years old or over with acute lymphoblastic leukemia and non-Hodgkin lymphoma who received at least one outpatient infusion of HDMTX without drug level monitoring were included. This is a retrospective, nested case-control study, in which the cases comprised patients who developed AKI after HDMTX.

Results: Overall, 302 patients were included, encompassing 840 infusions. Hospitalization occurred in 8.6 %. A total of 25 patients presented AKI after HDMTX administration, corresponding to 3 % of the methotrexate (MTX) infusions and 8.3 % of the patients. HIV-associated Burkitt lymphoma was more common in patients who presented AKI (18 vs. 6.8 %, p = 0.03). Baseline factors related to AKI after HDMTX were age > 44 y, body surface area ≥ 1.76 m², body mass index (BMI) ≥ 23.8 kg/m², glomerular filtration rate, and thrombocytopenia (< 150×10⁹/L). Multivariable analysis for adjusting such factors found that BMI was independently related to AKI after HDMTX (OR 3.8). Death after AKI occurred in 56 %.

Conclusion: Our data showed a similar rate of AKI after HDMTX to that reported in the literature, even without drug monitoring. However, patients who developed AKI in our cohort fared worse than expected, with more hospitalizations and death. A higher BMI was associated with the MTX-induced AKI in our cohort, suggesting a differential drug clearance and the need for specific guidelines for obese patients.

Keywords: Body mass index; Drug-induced nephrotoxicity; Leukemia; Lymphoma; Methotrexate.