Incidence of Clostridium Difficile-Induced Diarrhea in Patients Treated with High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma and Multiple Myeloma.

Introduction: Diarrhea is a major cause of morbidity and discomfort for patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT). There are multiple causes of diarrhea in patients undergoing APBSCT including chemotherapy, medications, and infection. The incidence of C. difficile-associated diarrhea (CDAD) in patients undergoing APBSCT has been reported to be in the range of 5 to 7%. A preliminary analysis from our group showed that patients with multiple myeloma had a higher incidence of CDAD than previously reported (Restrepo et al, Biol Blood Marrow Transplant 2002, 8:104). Purpose: To compare the incidence of CDAD in subjects treated with high-dose chemotherapy and APBSCT for multiple myeloma and lymphoma, and to identify risk factors for the development of CDAD. Methods: Retrospective analysis of 244 medical records of patients who underwent APBSCT for multiple myeloma and lymphoma from October 1996 until October 2001 at our institution. CDAD was defined as diarrhea with detectable C. difficile toxin A in stool. Patient-, disease- and transplant-related parameters analyzed included age, sex, race, performance status, diagnosis, agents utilized for PBSC mobilization, conditioning regimen, amount of CD34-positive cells infused, use of growth factors, presence and duration of fever, presence and duration of neutropenia, antimicrobial therapy and the frequency of testing for the presence of C. difficile toxin in stool were analyzed. Results: Diarrhea was reported in 157 subjects. One hundred and thirty-five subjects were tested for the presence of C. difficile toxin A and comprise the study group. The incidence of CDAD in this cohort was 15% (21 patients). Of the 21 patients, 14 (67%) had multiple myeloma and 7 (33%) had lymphoma. The use of cephalosporins (P=0.011), use of intravenous vancomycin (P=0.021), and the use of cyclophosphamide as part of the mobilization regimen (P=0.013) were the only risk factors associated with the development of CDAD. Conclusion: The incidence of CDAD at our institution was twice that previously reported. Antibiotic therapy with cephalosporins and intravenous vancomycin was associated with the development of CDAD, as well as the use of cyclophosphamide as part of the mobilization regimen. Although the incidence of CDAD in patients with multiple myeloma was higher than in patients with lymphoma, this difference did not attain statistical significance. Patients tested for C. diff Patients with positive tests P values Sex: NS Male 123 (91.1%) 20 (95.2%) Age: NS Mean (Range) 55 (22 to 78) 56 (22 to 78) Diagnosis: NS Myeloma 72 (53.3%) 14 (66.7%) Lymphoma 63 (46.7%) 7 (33.3%) Mobilization regimen: 0.013 GF 51 (37.7%) 9 (42.8%) GF+Cy 46 (34.1%) 9 (42.8%) GF+Tx 34 (25.2%) 1 (4.8%) Other 3 (2.2%) 2 (9.6%) NK 1 (0.8%) 0 (0%) Conditioning regimen: NS CVB 54 (40%) 7 (33.3%) Melphalan 50 (37%) 11 (52.4%) Bu/Mel 9 (6.7%) 1 (4.8%) Bu/Cy 9 (6.7%) 1 (4.8%) Other 13 (9.6%) 1 (4.8%) Antimicrobials Penicillins 20 (14.8%) 2 (9.5%) NS Cephalosporins 28 (20.7%) 9 (42.9%) 0.011 Vancomycin 36 (26.7%) 10 (47.6%) 0.021 Aminoglycosides 23 (17.0%) 5 (23.8%) NS Macrolides 7(5.2%) 0 (0.0%) NS Amphotericin B 6 (4.4%) 0 (0.0%) NS Other AB 1 (0.7%) 0 (0.0%) NS