Contribution of Clostridium difficile infection to the development of lower gastrointestinal adverse events during autologous stem cell transplantation.

BACKGROUND: Lower gastrointestinal (GI) adverse events (LGAE) are common afflictions of patients undergoing stem cell transplantation (SCT). Unfortunately, the pathophysiology remains poorly characterized. Emerging data suggest a prominent role of intestinal microbiota; however, contributions of pathogenic gut microbiota such as Clostridium difficile are not well defined. We performed a genome-wide association study (GWAS) to investigate clinical and genetic factors associated with development of LGAE. METHODS: A total of 972 patients undergoing autologous SCT were graded for LGAE based on Common Terminology Criteria for Adverse Events (v 4.0). Germline DNA material was obtained from leukapharesis products and genotyped using Illumina(®) Whole Genome Genotyping Infinium chemistry and HumanOmni1-Quad Bead chips containing over 1.1 million single nucleotide polymorphisms (SNPs) (Illumina, San Diego, California, USA). Statistical models incorporating clinical factors, genetic factors, and a combination of clinical plus genetic factors were utilized to compare patients who developed severe LGAE (grade 2 or above) and others. RESULTS: Among 972 patients, 459 (47.2%) developed severe LGAE. Baseline hemoglobin and hematocrit, estimated glomerular filtration rate, ß2-microglobulin, protocol type, and C. difficile infection (CDI) were associated with severe LGAE on univariate analysis, Genomic comparisons between groups did not reveal any SNPs associated with severe LGAE and neither did incorporation of genetic factors into the clinical model. In addition, 11 candidate SNPs associated with upper GI mucositis were evaluated, alongside clinical factors in a multivariate model. Only CDI was found to be associated with severe LGAE in all models. CONCLUSION: CDI is a prominent factor in the development of LGAE in patients undergoing autologous SCT.

Risk factors, preemptive therapy, and antiperistaltic agents for Clostridium difficile infection in cancer patients.

BACKGROUND: Clostridium difficile infection (CDI) is a serious complication of chemotherapy including high-dose regimens with autologous stem cell transplantation (ASCT). Antiperistaltic agents are contraindicated in CDI and preemptive CDI therapy is not recommended. We assessed the incidence, risk factors, and outcomes of CDI in patients with newly diagnosed multiple myeloma (MM) receiving similar antineoplastic therapy and supportive care including antiperistaltic agents and preemptive CDI antibiotics for significant diarrhea. METHODS: A total of 303 consecutive MM patients (2004-2007) were enrolled in a protocol consisting of induction chemotherapy, tandem melphalan (MEL)-ASCT, and consolidation. Patients with grade 2-4 diarrhea were simultaneously tested for CDI, and initiated on antiperistaltic agents (loperamide) and preemptive anti-CDI therapy. Risk factors, including prior CDI and MM immunoglobulin (Ig) isotype, were evaluated. Multinomial logistic regression was used to compute the relative risk ratio (RRR) and 95% confidence intervals (CIs). RESULTS: There were 43 cases of CDI (14.2%) during 1529 chemotherapy courses (536 ASCT). IgA MM protected against CDI (RRR 0.35; 95% CI 0.13-0.93, P = 0.04) whereas CDI during first induction markedly increased the risk of recurrence during second induction (RRR = 10.94; 95% CI 1.90, 62.92, P = 0.01) and following MEL-ASCT (RRR = 6.63; 95% CI 1.51, 29.12, P = 0.01). No CDI-related surgical intervention or death ensued despite use of antiperistaltic agents. CONCLUSIONS: CDI was not uncommon in cancer patients receiving chemotherapy. IgA myeloma appears to be protective. Concurrent antiperistaltic (loperamide) and preemptive CDI therapies were associated with excellent outcomes. Prior CDI history increased the risk for recurrence during successive chemotherapy courses.

Clinical and Health Care Utilization Outcomes of Kidney Transplantation in HIV-Positive Recipients: A Nationwide Analysis From 2008-2013.

BACKGROUND: Kidney transplantation (KTxp) provides dialysis independence, improved quality of life, and prolonged life expectancy for patients with end-stage renal disease. Before and during the early antiretroviral therapy era, KTxp was not a consideration for patients with end-stage renal disease who were HIV-positive (HIV+ve) given their short life expectancy and prevailing organ procurement constraints. Recent advancements in antiretroviral therapy and HIV care have overhauled this paradigm and KTxp has now been performed for several years, however, pragmatic studies documenting outcomes are lacking. We herein document the effectiveness of KTxp in patients who are HIV+ve by reporting clinical and health care utilization outcomes in the United States. METHODS: Utilizing the Inpatient Databases of the Healthcare Cost & Utilization Project spanning 2008-2013, we identified all adult recipients of KTxp by procedural codes and recipients who are HIV+ve by ICD-9 codes. We extracted demographic, clinical, and resource utilization variables and compared recipients who are HIV+ve with those who are HIV-negative (HIV-ve). We then performed descriptive statistics and multivariate analysis using logistic regression to assess the effect of HIV on clinical and utilization outcomes. RESULTS: A total of 104,137 patients had kidney transplants during the study period. Of the total, 605 patients were HIV+ve. Infections rates were similar among patients who were HIV+ve and HIV-ve (odds ratio [OR] 1.18, confidence interval [CI] 0.58-2.40; P = .652). In-hospital mortality rates were also similar (OR 0.83, CI 0.18-3.69; P = .80). Hospital charges for patients who were HIV+ve were no different from patients who were HIV-ve ($195,099 ± 1074 vs $186,567 ± 9558; P = .38). CONCLUSION: Clinical and fiscal outcomes are comparable among patients who are HIV+ve and HIV-ve during transplant hospitalization.

Late-Onset Allograft Aspergillosis in an HIV-Positive Renal Transplant Recipient: A Case Report.

Aspergillus infection of the allograft in renal transplant patients is rare and associated with a high mortality. We report a case of a 21-year-old, human immunodeficiency virus-positive, deceased-donor kidney recipient who presented 1 year after transplant with oliguric kidney injury. A nuclear medicine renal scan revealed absence of flow to the transplanted kidney, and a urine fungal culture was positive for Aspergillus flavus. The diagnosis was confirmed with the presence of fungal hyphae along with thrombosis in the vascular structures in renal allograft pathology. We found no evidence of disseminated aspergillosis or involvement of any other organ in the patient. To our knowledge, this case is the first reported in the literature of late-onset non-disseminated renal-limited aspergillosis in a human immunodeficiency virus-positive renal transplant patient.

Renal insufficiency retains adverse prognostic implications despite renal function improvement following Total Therapy for newly diagnosed multiple myeloma.

Renal insufficiency (RI) is a frequent complication of multiple myeloma (MM) with negative consequences for patient survival. The improved clinical outcome with successive Total Therapy (TT) protocols was limited to patients without RI. We therefore performed a retrospective analysis of overall survival, progression-free survival and time to progression (TTP) of patients enrolled in TT2 and TT3 in relationship to RI present at baseline and pre-transplant. Glomerular filtration rate was graded in four renal classes (RCs), RC1-RC4 (RC1 ⩾90 ml/min/1.73 m(2), RC2 60-89 ml/min/1.73 m(2), RC3 30-59 ml/min/1.73 m(2) and RC4 <30 ml/min/1.73 m(2)). RC1-3 had comparable clinical outcomes while RC4 was deleterious, even after improvement to better RC after transplant. Among the 85% of patients with gene expression profiling defined low-risk MM, Cox regression modeling of baseline and pre-transplant features, which also took into consideration RC improvement and MM complete response (CR), identified the presence of metaphase cytogenetic abnormalities and baseline RC4 as independent variables linked to inferior TTP post-transplant, while MM CR reduced the risk of progression and TTP by more than 60%. Failure to improve clinical outcomes despite RI improvement suggested MM-related causes. Although distinguishing RC4 from RC<4, 46 gene probes bore no apparent relationship to MM biology or survival.