Clostridium difficile (C. difficile) infection was observed in 13% of recipients after hematopoietic stem cell transplantation (HSCT), mainly in the first month posttransplantation. Risk factors were cord blood as the source of stem cells, acute graft-versus-host disease (GVHD), and total body irradiation (TBI). No association was found with an increased risk of mortality. The purpose of this study was to evaluate the incidence, risk factors, and outcome of C. difficile infection (CDI) after HSCT. We conducted a single-center, retrospective, cohort study on all patients who received an allogeneic HSCT from January 2004 to December 2007. All patients with diarrhea in the first year after HSCTwere tested for the presence of C. difficile in stools. Among the 407 assessable patients, 53 presented at least 1 CDI in the first year post-HSCT. The total incidence rate was 5.6 cases of CDI per 10,000 patient-days. Fifty percent of cases were diagnosed in the first month after HSCT, and 95% occurred during the first 6 months. Fewer than 5% of patients with CDI had severe diarrhea and severe complications were never observed. TBI in the conditioning regimen, cord blood as the source of stem cells, and acute graft-versus-host disease (aGVHD) were independently associated with CDI. Six patients (11%) had a recurrence of CDI. Four patients required second-line treatment with vancomycin. With a median follow-up of 22 months, the 2-year overall survival rates were similar between patients who presented a CDI and those who did not. CDI was observed in approximately 13% of recipients after HSCT, mainly in the first month posttransplantation and was associated with CB, aGVHD, and TBI. CDI was not associated either with severe complications or with an increased risk of mortality in this large cohort of patients.

The online version of this article has a Supplementary Appendix. BackgroundDue to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination of cyclophosphamide and antithymocyte globulin. We report the long-term follow up of patients who underwent hematopoietic stem cell transplantation from an HLAmatched sibling donor after this conditioning regimen. Design and MethodsWe analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following conditioning with cyclophosphamide (200 mg/kg) and antithymocyte globulin (2.5 mg/kg/day x 5 days). ResultsMedian age was 21 years (range 4-43); 41 of the 61 patients were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 patients received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II-IV graft-versus-host disease was 23% (95%CI 13-34) and 18 developed chronic graft-versus-host disease (cumulative incidence 32% at 72 months, 95% CI 20-46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic graft-versus-host disease (P=0.017). With a median follow up of 73 months (range 8-233), the estimated 6-year overall survival was 87% (95% CI 78-97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin's lymphoma) during follow up. ConclusionsCyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction.Key words: hematopoietic stem cell transplantation, severe aplastic anemia, long-term outcomes. Haematologica 2012;97(5):710-716. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Konopacki J, Porcher R, Robin M, Bieri S, Cayuela J-M, Larghero J, XhaardLong-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning

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