Methotrexate-induced acute kidney injury in patients with hematological malignancies: three case reports with literature review

Abstract Background High-dose methotrexate (HD-MTX) therapy has been used to treat a wide range of oncological malignancies. While the therapy can be tolerated with hydration, urine pH control, and leucovorin rescue therapy, HD-MTX is cytotoxic and can cause renal failure. There have been several case reports of HD-MTX toxicity in patients with solid tumors; however, few case series of hematological malignancies have been published. Patients with hematological malignancies tend to be administered many concomitant drugs, which can affect the elimination of MTX and result in acute kidney injury. Case presentation Here, we present three cases of HD-MTX-induced acute kidney injury in patients with hematological malignancies. Several blood purification methods were used to attempt to eliminate MTX. Conclusions Rapid elimination of MTX is needed for patients with higher serum MTX concentrations to avoid additional cytotoxic effects, especially in patients who have experienced many complications. Although the most effective method for MTX elimination remains unknown, the results of our retrospective survey suggest that combined modalities, such as hemodialysis and plasma exchange, may be suitable for treatment of patients with hematological malignancies

Distinct gene alterations with a high percentage of myeloperoxidase-positive leukemic blasts in de novo acute myeloid leukemia

The myeloperoxidase (MPO)-positivity of blasts in bone marrow smears is an important marker for not only the diagnosis, but also the prognosis of acute myeloid leukemia (AML). To investigate the relationship between genetic alterations and MPO-positivity, we performed targeted sequencing for 51 genes and 10 chimeric gene transcripts in 164 newly diagnosed de novo AML patients; 107 and 57 patients were classified as AML with >50% MPO-positive blasts (MPO-high group) and ?50% MPO-positive blasts, (MPO-low group), respectively. The univariate analysis revealed that RUNX1-RUNX1T1 (P < 0.001), the KIT mutation (P < 0.001), and CEBPA double mutation (P = 0.001) were more likely to be found in the MPO-high group, while the DNMT3A mutation (P = 0.001), FLT3 tyrosine kinase domain mutation (P = 0.004), and TP53 mutation (P = 0.020) were more likely to be present in the MPO-low group. Mutations in genes related to DNA hypermethylation signatures (IDH1, IDH2, TET2, and WT1 genes) were more frequent in the MPO-high group (P = 0.001) when patients with fusion genes of core-binding factors were excluded from the analysis. Our results suggest that MPO-positivity of blasts was related with the distinct gene mutation patterns among de novo AML patients