Work

Long term infectious complications following reduced intensity conditioning (RIC) allogeneic HLA-identical sibling transplantation (allo-SCT)

Year: 2005

Type: article

Abstract: We analyzed infections occurring beyond 6 months after allo-SCT, in 81 consecutive pts who received a RIC prior to allo-SCT from HLA-identical siblings: median age was 49 (18–63) years. 33 (41%), 34 (42%) and 14 (17%) pts had respectively a myeloid, lymphoid or non-hematological malignancy. 62 pts (77%) had an advanced disease with high risk clinical features precluding the use of standard myeloablative allo-SCT. 21 pts (26%) BMT and 60 (74%) PBSCT. RIC consisted of fludarabine and busulfan with ATG (high dose: 20 (25%); low dose: 50 (62%)) or of low dose irradiation-based RIC (N=11, 13%). With 26 (9–68) months follow-up, 67 pts (83%) experienced at least one infectious episode beyond the first six months after allo-SCT developing at a median of 8 (6–34) months. 221 infectious episodes were observed, of which 123 (56%) required hospitalization and systemic anti-microbial therapy. 94 episodes (43%) could be documented (bacterial, n=28; viral, n=56; fungal, n=10). Documented infections were: gram negative bacteria (16%), other bacteria (14%), CMV positive antigenemia (17%), HSV (25%), VZV (15%), other viruses (3%), aspergillus (4%), candida species (6%). 81% pts (n=54) with an infection were under systemic immunosuppressive therapy for chronic GVHD. Moreover, 24 pts (30%) experienced >1 episode of documented infections (median, 2 episodes; range, 1–12). In a univariate analysis performed in the pts with documented infection, age <50 (P=0.06), the use of PBSCs as stem cell source (P=0.03) and a history of DLI (P=0.002), exerted a protective effect against infection occurrence. In a multivariate analysis, DLI was significantly associated with a decreased risk of long term infections (P=0.002; RR=0.23; 95% CI, 0.1–0.6), indirectly highlighting the protective effect of donor origin immunity after allo-SCT. In this series of pts surviving at least 6 months after RIC allo-SCT, the overall long term transplant-related mortality was 14% (n=11), of whom 6 deaths were attributed to infections (3 bacterial septicemia, 2 aspergillosis, 1 pneumocystosis), giving a cumulative incidence of long term-infectious related mortality of 7% (95% CI, 1.4–12.6%). Obviously, prospective efforts to develop optimal antimicrobial preventive strategies after RIC allo-SCT are still needed. However, the results from this analysis compare favorably with data from the standard myeloablative allo-SCT setting.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2004.12.069