Fatal Infectious Complications Developing Late after Allogeneic Stem Cell Transplantation.

Background and aim: The procedure of allogeneic stem cell transplantation (SCT) has evolved during the past decades. Infectious complications are still a major problem contributing to the transplantation related mortality (TRM). The epidemiology and outcome of early infections after SCT are well described. However, less is known has about late infections after SCT. Thus, the aim of this study was to determine risk factors for fatal infections occurring later than 6 months after allogeneic SCT.

Material and methods: Our study is based on 938 consecutive SCT patients transplanted 1976–2003 of whom 688 (73%) had survived for at least 6 months after SCT. A retrospective chart review was performed identifying 44 (6.4%) patients surviving for at least 6 months, having died from infection. Patients who had relapsed in their malignant disease were excluded. A control group of 176 patients (4 per case) was identified using relapse-free survival for at least 6 months and year of SCT as the matching criteria. Five controls were excluded leaving 171 patients in the control population. Risk factors for death from late infections were identified by logistic regression.

Results: 29 patients (66%) developed their fatal infection within 18 months and 37 (84%) within 5 years after SCT. 37 patients (84%) had ongoing chronic graft versus host disease (GVHD) and 36/44 (82%) had ongoing immunosupression at the time of death. 57 controls had died after 6 months from SCT; 32 of 57 from relapse. Comparing patients and controls in univariate analyses, the mean age was 30.6 years in the cases and 26.5 years in the controls (p=.13). 22/44 (50%) cases had been transplanted from an unrelated or mismatched donor, compared to 57/171 (33%) controls, p=.053; and 35/44 (80%) cases had received a conditioning regimen including myeloablative dose of TBI compared to 113/171 (66%) in the control group, p<.05). Regarding post-transplant complications 40/44 (91%) cases had experienced cGVHD compared with 101/171 (59%) controls, p<.001. 21/44 (48%) cases had developed obstructive respiratory dysfunction compared with 46/171 (27%) controls, p=.01; and more cases (33/44; 75%) than controls (85/171; 50%;) had experienced CMV infection. In multivariate analysis chronic GVHD (OR 9.2; p<.001), use of a mismatched or unrelated donor (OR 4.8; p<.001), and having had a CMV reactivation (OR 8.3; p=.004) increased the risk. Age, acute GVHD, TBI or obstructive respiratory dysfunction had no significant impact on the risk for late fatal infection.

Conclusion: Infections later than 6 months after SCT are important contributors to late TRM. Risk factors for late fatal infections include chronic GVHD, use of alternative donors and CMV infection.