Predictors and outcomes of dose reduction of methotrexate and cyclosporin graft-versus-host disease prophylaxis following allogeneic haemopoietic cell transplantation.

BACKGROUND: Concern regarding dose-related toxicities of methotrexate (MTX) and cyclosporin (CYA) graft-versus-host disease (GVHD) prophylaxis occasionally leads to dose alterations post allogeneic haemopoietic cell transplant (alloHCT). AIMS: To clarify causes of MTX and CYA dose alteration and assess impact on patient outcomes, including GVHD, relapse, non-relapse mortality (NRM) and overall survival (OS). METHODS: Analysis of retrospective data was performed in a single tertiary centre of patients who underwent alloHCT for any indication and who received GVHD prophylaxis with CYA and MTX between the years 2011 and 2015. Univariate analysis was conducted using the log-rank test for OS and using competing risk regression for NRM, relapse and GVHD. Fisher exact tests were used to determine if an association existed between each of the pre-transplant variables and MTX alteration. Multivariate models for OS and NRM were constructed using Cox proportional hazards modelling and competing risk regression respectively. RESULTS: Fifty-four (28%) of 196 had MTX alterations and 61/187 (33%) had CYA alterations. Reasons for MTX alteration included mucositis, renal or liver impairment, fluid overload and sepsis. Causes of CYA alteration were numerous, but most commonly due to acute kidney impairment. MTX alteration was associated with inferior OS (hazard ratio 2.4; P = <0.001) and higher NRM (odds ratio (OR) 4.6; P < 0.001) at 6 years post-landmark. CYA alteration was associated with greater NRM (OR 2.7; P = 0.0137) at 6 years. GVHD rates were unaffected by dose alteration. CONCLUSIONS: Our findings suggest dose alteration in MTX and CYA GVHD prophylaxis is associated with adverse survival outcomes in alloHCT, without a significant impact on GVHD rates.

A Person-Focused Analysis of Resilience Resources and Coping in Diabetes Patients.

This study investigated the resilience resources and coping profiles of diabetes patients. A total of 145 patients with diabetes completed a questionnaire packet including two measurements of coping (COPE and Coping Styles questionnaires), and personal resources. Glycosylated hemoglobin (HbA(1c)) was also assessed. Resilience was defined by a factor score derived from measures of self-esteem, self-efficacy, self-mastery, and optimism. All of the maladaptive coping subscales were negatively associated with resilience (r's range from -.34 to -.56, all p's <.001). Of the adaptive coping subscales, only acceptance, emotional support, and pragmatism were positively associated with resilience. The upper, middle, and lower tertiles of the resilience factor were identified and the coping profiles of these groups differed significantly, with low resilience patients favoring maladaptive strategies much more than those with high or moderate resilience resources. Resilience groups did not differ in HbA(1c) levels; correlation coefficients of the coping subscales with HbA(1c) were explored. This study demonstrates a link between maladaptive coping and low resilience, suggesting that resilience impacts one's ability to manage the difficult treatment and lifestyle requirements of diabetes.