Outcomes of Allogeneic HSCT for Patients with Hematologic Malignancies (AML, ALL, MDS, CML) with and without Pre-Existing Fungal Infections: A Cibmtr Study

Invasive fungal infections (IFI) are associated with a high mortality rate in patients undergoing hematopoietic stem cell transplantation (HSCT).  However, with availability of new antifungal agents with lower toxicity profiles and implementation of reduced intensity transplants (RIT), patients with previously documented, proven or probable IFI are increasingly undergoing HSCT.  Recognizing these practice changes, the clinical outcomes of patients with pre-existing IFI, diagnosed prior to allogeneic HSCT, (n= 825) were compared to a similar cohort of patients from the same HSCT centers over the past decade without proven or probable pre-transplant IFI (n=10,247), for outcomes of treatment related mortality (TRM), relapse rates, overall survival (OS), disease free survival (DFS) and the development of post-transplant IFI.  Primary analysis focused on outcomes between 2001-2009, with a secondary analysis limited to AML and ALL patients receiving myeloablative conditioning extending from 1995 to 2009, prior to availability of novel antifungal agents, and the emergence of PBSC allografts.  Patients with pre-transplant IFI were older, have lower performance status, have advanced disease, carry the diagnosis of AML, receive a cord blood transplant, receive RIT, receive mold-active fungal prophylaxis and be transplanted more recently.  Aspergillus and Candidal infections were the most commonly identified pre-transplant IFI and 68% of patients presented with pulmonary involvement.  Univariable outcomes analysis reveals lower 1-year, 3-year, and 5-year DFS and OS for patients with pre-transplant IFI (Table 1).  Relapses were higher in this cohort and there was a trend to increased TRM.  The probability of post-transplant fungal infection was 24% for the study group and 17% for the control group (p <0.001). Interestingly, cause of death was associated with a greater likelihood of having recurrent/ persistent disease.  Infectious mortality causes were only slightly increased (13 vs 9%) between the study group and the control group. With regard to the 2^o analysis comparing patients with pre-transplant IFI diagnosed between 1995 -2000 vs 2001-2009, TRM @ 1, 3, 5 yrs was significantly higher with associated reduction in OS and DFS for the early cohort. However, there were no observable differences in IFI post-transplant and in relapse rates.

Conclusions: Documentation of pre-HSCT IFI is associated with lower DFS and OS after allogeneic HSCT.  However, mortality is most influenced by patients with more advanced disease status than infectious etiologies.  Treated pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT.