Clostridioides difficile infection in non-transplanted adults with haematological malignancy: Systematic review and meta-analysis on behalf of European Conference on Infections in Leukemia (ECIL) and Infectious Diseases Working Party (IDWP) of the European Society for Blood and Marrow Transplantation (EBMT).
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Clostridioides difficile infection (CDI) is a frequent complication in patients with haematological malignancies (HM). No meta-analysis on its incidence and outcomes in non-transplanted adults with HM is available. Pubmed/Medline database was searched for articles published between 2010 and 2026 to reflect current epidemiology. Studies including exclusively children or haematopoietic cell transplant recipients (HCT-r) were not included. Pooled estimates were calculated using a random-effects model with DerSimonian and Laird (DL) variance, and Paule-Mandel tau2 and Hartung-Knapp-Sidik-Jonkman (PM-HKSJ) estimations. Thirty-one studies were included, and eighteen studies with data from 1,766,024 non-transplanted HM adults were identified to assess the pooled incidence of CDI, being 5.55% (95% CI, 3.71-8.22). The incidence of CDI was significantly higher among patients with acute leukemia (8.33%, 95%CI 6.24-11.04) than those with chronic HM (2.62%, 95% CI 2.31-2.96, p < 0.001). Among 1047 patients with CDI, the incidence of recurrent CDI was 16.30% (95% CI, 13.80-19.16). The pooled incidence of severe and severe-complicated CDI was 14.49% (95% CI, 11.72-17.78) and 4.60% (95% CI, 2.17-9.47), respectively. Among 54,394 HM patients with CDI, the incidence of all-cause mortality was 20.49% (95% CI, 18.41-22.75), and the CDI-related mortality was 10.49% (95% CI, 6.57-16.33). High heterogeneity of studies was observed. In the sensitivity analyses, the rates were similar or higher when studies including also HCT-r were excluded. CDI is frequent in patients with HM, particularly in those with acute leukemia. The rate of recurrence was similar to other populations. Low rate of severe CDI might stem from the lack of severity criteria applicable to HM population, or from the lack of inflammatory response in neutropenic patients. The considerable all-cause mortality highlights that CDI might be one of various factors associated with poor prognosis in this population, which deserves specific strategies for CDI prevention and treatment.