Evaluation of Risk Factors for Clostridium difficile Infection in Hematopoietic Stem Cell Transplant Recipients.

STUDY OBJECTIVES: The primary objective was to determine the impact of hematologic malignancies and/or conditioning regimens on the risk of developing Clostridium difficile infection (CDI) in patients undergoing hematopoietic stem cell transplantation (HSCT). Secondary objectives were to determine if traditional CDI risk factors applied to patients undergoing HSCT and to determine the presence of CDI markers of severity of illness among this patient population. DESIGN: Single-center retrospective case-control study. SETTING: Quaternary care academic medical center. PATIENTS: A total of 105 patients who underwent HSCT between December 2009 and December 2014; of these patients, 35 developed an initial episode of CDI (HSCT/CDI group [cases]), and 70 did not (controls). Controls were matched in a 2:1 ratio to cases based on age (± 10 yrs) and date of HSCT (± 6 mo). MEASUREMENTS AND MAIN RESULTS: Baseline characteristics of the two groups were well balanced regarding age, sex, race, ethnicity, and type of HSCT. No significant differences in conditioning regimen, hematologic malignancy, total body irradiation received for HSCT, use of antibiotics within 60 days of HSCT, or use of prophylactic antibiotics after HSCT were noted between the two groups. Patients in the control group were 10.57 (95% confidence interval 1.24-492.75) more likely to have received corticosteroids prior to HSCT than patients in the HSCT/CDI group (p=0.01). Use of proton pump inhibitors at the time of HSCT was greater among the control group than among patients in the HSCT/CDI group (97% vs 86%, p=0.048). No significant difference in mortality was noted between the groups at 3, 6, and 12 months after HSCT. Metronidazole was frequently prescribed for patients in the HSCT/CDI group (34 patients [97%]). Severe CDI was not common among patients within the HSCT/CDI group (13 patients [37%]); vancomycin was infrequently prescribed for these patients ([31%] 4/13 patients). CONCLUSION: Hematologic malignancies and a conditioning regimen administered for HSCT were not significant risk factors for the development of CDI after HSCT. Use of corticosteroids prior to HSCT and use of proton pump inhibitors at the time of HSCT were associated with a significantly decreased risk of CDI.

Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens.

Uncontrolled delayed nausea and vomiting remains a problem after high-dose preparative regimens used for autologous and allogeneic hematopoietic stem cell transplants. Recently, aprepitant was approved for highly and moderately emetogenic chemotherapy, and, in particular, is effective for decreasing delayed emesis. To evaluate its safety and efficacy in the transplantation setting, we performed a randomized, placebo-controlled, phase 3 trial of aprepitant in combination with ondansetron and dexamethasone in patients treated with ablative preparative regimens. Patients were randomized to receive oral aprepitant or placebo daily with oral ondansetron and dexamethasone during and for 3 days after the completion of the preparative regimen in this prospective randomized, double-blind study. The primary objective was complete response (CR) rate, defined as no emesis with no or mild nausea. Other endpoints included number of emetic episodes, nausea severity assessed using a 100-mm visual analog scale (VAS), the need for rescue antiemetics, and transplantation outcome, including regimen-related toxicity. One hundred eighty-one patients were randomized and 179 patients were eligible for analysis. Overall, CR rates were 81.9% for the aprepitant and 65.8% for the placebo arms (P < .001). Percentages of patients with no emesis all days were 73.3% for aprepitant and 22.5% placebo (P < .001). Mean VAS scores were 16.6 mm aprepitant and 16.9 mm placebo (NS), and there were no differences in the amount of rescue antiemetics used, regimen related toxicity, engraftment, or transplantation outcome. Aprepitant in combination with dexamethasone and ondansetron significantly decreased emesis and significant nausea, whereas not increasing RRT or affecting short-term survival but had no significant impact on the use of PRN antiemetics, or overall VAS nausea scores.

Randomized phase III trial of pegfilgrastim versus filgrastim after autologus peripheral blood stem cell transplantation.

Nonrandomized trials suggest that pegfilgrastim, a pegylated granulocyte colony-stimulating factor, could be used in lieu of filgrastim after autologus peripheral blood stem cell transplantation. This phase III, randomized, double-blinded, placebo-controlled trial compared the efficacy, costs, and safety of single-dose pegfilgrastim (single 6 mg dose) versus daily filgrastim (5 microg/kg/day) for this indication. Seventy-eight patients, matched for age, sex, underlying disease, stage, and CD34/kg transplant dose were enrolled. Cytokines were started on day +1 posttransplant and continued to an absolute neutrophil count (ANC) of 5x10(9)/L for 3 days or 10x10(9)/L for 1 day. The median time to neutrophil engraftment (ANC >1.5x10(9)/L for 3 days or 5x10(9)/L for 1 day) was the same in both groups (12 days). No differences in platelet engraftment (11 versus 13 days), number of platelet transfusions (5 versus 4), percent with positive cultures for bacterial pathogens (23% versus 15%), days of fever (1 versus 2), deaths prior to engraftment (1 versus 1), or duration of hospital stay (19 versus 19 days) were seen between the pegfilgrastim and filgrastim groups, respectively. Using the average wholesale price for doses used in this trial, there was a per-patient savings of $961 for the pegfilgrastim group (P < .001). This phase III study failed to demonstrate a difference in time to neutrophil engraftment or any clinical sequelae between pegfilgrastim and filgrastim when given post-APBSCT, with pegfilgrastim achieving a cost savings over filgrastim.