Risk factors for high-dose methotrexate-induced nephrotoxicity.

High-dose methotrexate (MTX) is widely used for the treatment of hematological malignancies. Despite the application of routine supportive care measures, such as intensive fluid hydration and urine alkalinization, nephrotoxicity is still a problem. The present study aimed to evaluate the risk factors for MTX-induced nephrotoxicity. We retrospectively reviewed 88 patients who received a regimen consisting of high-dose MTX (1000 mg/m2) and cytosine arabinoside between 2006 and 2018. Nephrotoxicity (≥ grade 2) was observed in 11 patients. Nephrotoxicity was observed only in patients with a high MTX concentration. Other than the MTX concentration, the serum uric acid level and urine pH at day 1 were associated with nephrotoxicity. A multivariate analysis revealed that urine pH was an independent risk factor for MTX-induced nephrotoxicity. Urine pH < 7.0 at day 1 was a significant risk factor for nephrotoxicity (odds ratio, 8.05; 95% confidence interval 1.95-33.3) and was also a predictor of delayed MTX elimination at 72 h after injection. Among pre-treatment factors, a low serum calcium level predicted urine pH < 7.0 at day 1. In conclusion, the present study suggests that low urine pH at day 1 is an independent risk factor for MTX-induced nephrotoxicity.

CD25 as an adverse prognostic factor in elderly patients with acute myeloid leukemia.

OBJECTIVES: CD25 has been reported to be highly expressed in leukemia stem cells and correlated with adverse outcomes in young patients with acute myeloid leukemia (AML). However, the significance of CD25 expression in elderly patients with AML has not yet been investigated. METHODS: We retrospectively analyzed 154 newly diagnosed AML patients aged 60 years or over by flow cytometry. RESULTS: CD25-positive AML was characterized by high white blood cell counts, secondary AML, rare favorable karyotypes, and positivity for CD34 and CD7 antigens, compared with CD25-negative AML. CD25 positivity was significantly correlated with an inferior complete remission (CR), event-free survival (EFS), and overall survival. Multivariate analysis showed CD25 positivity to be a significant prognostic predictor of CR and EFS. A regimen of low-dose cytarabine and aclarubicin combined with granulocyte-colony-stimulating factor (CAG) led to higher CR rates in the CD25-positive AML patients than intensive chemotherapies. CD25 expression was increased at relapse and in the development of leukemic status from myelodysplastic syndrome or myeloproliferative neoplasm. DISCUSSION: An effective treatment strategy for elderly patients with CD25-positive AML has not been established. Further studies are needed to evaluate the effect of a CAG regimen and allogenic stem cell transplantation in patients. CONCLUSION: CD25 is an independent prognostic factor in elderly AML patients. Alternative therapies for CD25-positive elderly AML patients are needed.

[Treatment with a proteasome inhibitor, bortezomib, for thalidomide-resistant multiple myeloma].

A proteasome inhibitor with a new molecular target (PS-341: bortezomib) was recently developed, and its efficacy in the treatment of refractory multiple myeloma has been reported in the United States. Here, we present a 54-year-old Japanese male patient with refractory multiple myeloma resistant to thalidomide. In 1998, the patient was diagnosed as having multiple myeloma (IgG-kappa) and underwent chemotherapy, autologous hematopoietic cell transplantation and interferon therapy, but the disease recurred. In December 2002, thalidomide and high-dose dexamethasone therapy was initiated, and while this combination therapy was effective at first, the multiple myeloma became unresponsive. On 23 June 2003, bortezomib therapy with the following regime was therefore started: 2.2 mg (1.3 mg/m2) of bortezomib was injected intravenously on days 1, 4, 8 and 11, and after a one-week break, another cycle was performed. Starting on day 8 of the administration, the serum total protein, IgG, serum calcium and LDH levels decreased rapidly, and after day 45 of the administration, blood transfusion was no longer needed. Since this is the first report of the use of bortezomib in the treatment of refractory multiple myeloma in Japan, further monitoring of this patient will provide extremely valuable information for developing a therapy against this disease.