Abstract：Objective To investigate the adverse effects of high-dose methotrexate (HDMTX) therapy, and to provide a theoretical basis for optimizing clinical treatment. Methods A retrospective analysis was performed for the clinical data of 120 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma who underwent 601 times of HDMTX therapy. The adverse effects of various systems were analyzed according to the WHO criteria for the classifcation of adverse effects of anticancer drugs. Results Almost all the children experienced bone marrow suppression, and 93.3% had granulocytopenia. The most common adverse effects in the digestive system and urinary system were elevated glutamic-pyruvic transaminase (60.4%) and proteinuria (9.2%) respectively. For skin symptoms, skin erythema had the highest incidence rate (7.2%). The adverse effects in the nervous system (hyperpathia, numbness of extremities, or headache) were only observed in 7 cases. Serious adverse effects were only seen in the blood system and digestive system. Compared with the 3 g/m2 methotrexate (MTX) group, the 5 g/m2 HDMTX group had a signifcantly higher 24-hour plasma MTX concentration, signifcant reductions in hemoglobin and platelet count, and signifcantly higher incidence rates of oral mucositis, proteinuria, and skin symptoms (P Conclusions Serious adverse effects of HDMTX therapy mainly involve the blood system and digestive system, and the adverse effects such as bone marrow suppression, oral mucositis, proteinuria, and skin symptoms occur in a dose-dependent manner.
Tsurusawa M, Gosho M, Mori T, et al. Statistical analysis of relation between plasma methotrexate concentration and toxicity in high-dose methotrexate therapy of childhood nonHodgkin lymphoma[J]. Pediatr Blood Cancer, 2015, 62(2):279-284.
[6]
Pauley JL, Panetta JC, Crews KR, et al. Between-course targeting of methotrexate exposure using pharmacokinetically guided dosage adjustments[J]. Cancer Chemother Pharmacol, 2013, 72(2):369-378.
[7]
Cwiklinska M, Balwierz W, Stanuch H. Clinical tolerance of high-dose methotrexate used in consolidation therapy in children with acute lymphoblastic leukemia[J]. Przegl Lek, 2010, 67(6):355-360.
Garcia-Puig M, Fons-Estupina MC, Rives-Sola S, et al. Neurotoxicity due to methotrexate in paediatric patients. Description of the clinical symptoms and neuroimaging fndings[J]. Rev Neurol, 2012, 54(12):712-718.
[11]
Bhojwani D, Sabin ND, Pei D, et al. Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia[J]. J Clin Oncol, 2014, 32(9):949-959.
[12]
Shah N, Zambidis ET. False-photosensitivity and transient hemiparesis following high-dose intravenous and intrathecal methotrexate for treatment of acute lymphoblastic leukemia[J]. Pediatr Blood Cancer, 2009, 53(1):103-105.
[13]
Millot F, Auriol F, Brecheteau P, et al. Acral erythema in children receiving high-dose methotrexate[J]. Pediatr Dermatol, 1999, 16(5):398-400.
[14]
Pugi A, Benemei S, Vietri M, et al. Anaphylaxis during the frst course of high-dose methotrexate:a case report and literature review[J]. J Clin Pharm Ther, 2012, 37(2):245-248.
