Risk factors and epidemiology of Clostridium difficile infection in hematopoietic stem cell transplant recipients during the peritransplant period.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients represent a high-risk group for developing Clostridium difficile (CD) infection (CDI). We aimed to identify specific risk factors for CDI in an HSCT patient population during the peritransplant period. METHODS: We performed a case-control study within a cohort of HSCT patients who received a transplant from November 2010 to March 2013. Cases had a clinical presentation compatible with CDI and a positive stool sample Xpert® C. difficile test. Controls were CDI negative and matched on age, gender, and transplant type. Peritransplant period was defined as -30 days or time of stem cell mobilization maneuver to 30 days post transplant in autologous SCT or 90 days post transplant in allogeneic SCT. RESULTS: Of 781 HSCTs performed during the study period, 650 (83.2%) had a stool sample submitted for CD testing. Eight-six (13.2%) cases with CDI were identified. Most of the cases were diagnosed within a week after transplantation (median of 5 days). In adjusted analysis, prior hospitalization (odds ratio [OR]: 2.01, 95% confidence interval [CI] 1.2-3.36), prior cephalosporin administration (OR 2.72, 95% CI: 1.54-4.83), and prior chemotherapy (OR: 3.26, 95% CI: 1.92-5.5) were significantly associated with CDI. CONCLUSIONS: Hospitalization, and prior antibiotic and chemotherapy use are risk factors that are not easily modifiable, which emphasizes the need to start investigating preventive or prophylactic strategies in this high-risk population.

Efficacy and tolerability of anthracycline-based therapy in elderly patients with diffuse large B-cell lymphoma.

INTRODUCTION: Although diffuse large B-cell lymphoma (DLBCL) can be cured with rituximab and anthracycline-based therapy, within the elderly population there are additional factors to consider in selecting a treatment regimen including comorbid conditions, decreased drug metabolism, decreased hematologic reserve, reduced performance status, and regimen-related toxicity. PATIENTS AND METHODS: We performed a retrospective cohort analysis of patients with DLBCL aged ≥ 65 years at time of diagnosis treated with either an anthracycline-containing regimen (ACR; n = 59) or a non-ACR (n = 13) to assess factors that led to treatment selection, tolerability, and outcomes. RESULTS: The mean age was 73 years in the ACR and 77 years in the non-ACR group (P = .009), and median left ventricular ejection fraction (LVEF) at diagnosis was 60% in the ACR group and 45% in the non-ACR group (P < .001). With an ACR, elderly DLBCL patients had a median overall survival of 28 months and a 2-year progression-free survival (PFS) of 64%. After an ACR, 14 patients [24%] (out of 59 total patients) had a decrease in LVEF, 7 patients [15%] (% is based off of those who we had the data collected, so this is out of 45 with this specific data) required a dose reduction of the anthracycline, and 15 patients [33%] (% is based off of those who we had the data collected, so this is out of 45 with this specific data) could not complete the regimen as planned. Hospitalization due to toxicity occurred in 20 patients [44%] (% is based off of those who we had the data collected, so this is out of 45 with data) of patients in the ACR group and 3 patients [75%] (% is based off of those who we had the data collected, so this is out of 4 with this specific data) in the non-ACR group, and was the only predictor of overall survival. CONCLUSION: Results of this study suggest that elderly patients with DLBCL experience meaningful PFS with ACRs, but a third experience toxicity requiring therapy modification. Future studies should examine larger patient populations and define treatments with outcomes similar to ACR that also decrease toxicity and hospitalization in the elderly DLBCL population.

Development of drug-resistant herpes simplex virus infection after haploidentical hematopoietic progenitor cell transplantation.

An unusually high incidence of acyclovir- and foscarnet-resistant herpes simplex virus (HSV) infection was noted after lymphocyte-depleted blood hematopoietic progenitor cell (HPC) transplantation from HLA-haploidentical family donors. Fourteen adults with hematologic malignancies underwent blood HPC transplantation from haploidentical family donors. Pheresis products were stringently depleted of T and B cells by immunomagnetic adsorption, and patients received no immunosuppression after transplantation. HSV reactivation occurred in all 7 evaluable HSV-1- or HSV-2-seropositive patients, at a median of 40 days after transplantation. Susceptibility testing of clinically resistant viral isolates demonstrated acyclovir resistance in all 5 cases tested. Second-line therapy produced only partial responses, and in vitro evidence of foscarnet resistance developed rapidly in all 3 patients treated with foscarnet. Healing of lesions coincided with T-cell recovery. The prolonged immunodeficiency associated with stringent lymphocyte depletion of the graft appears to strongly predispose to emergence of drug-resistant HSV. Furthermore, immune reconstitution is necessary for eradication of infection.