163: Systemic viral and fungal infections are not significantly decreased following reduced intensity allogeneic stem cell transplantation (RIAlloSCT) in children and adolescent recipients with malignant and nonmalignant diseases

Abstract

RIAlloSCT has been demonstrated to induce a high degree of mixed donor chimerism and a significant decrease in duration and nadir of neutropenia in the early post allograft period (Satwani/Cairo et al, BBMT, 2005). This reduction in duration of neutropenia has translated into a significant decrease in bacteremia during the first 30 days (Jungenhans et al, BBMT, 2002). It remains to be determined whether RIAlloSCT will also result in a decrease in systemic viral and invasive fungal infections, which are more dependent on alteration in cellular immunity. From 1/2001 to 7/2006, 58 pediatric pts with median age of 11.5 yrs (0.33-21) received RIAlloSCT for malignant (n=42) and non-malignant (n=16) diseases. RI conditioning was fludarabine based 150-180 mg/m2 + busulfan 6.4-12.8 mg/kg (n=42), or cyclophosphamide 30-120 mg/kg (n=14) or melphalan 70 mg/m2 (n=2) ± ATG (n=36) or alemtuzumab (n=8). Stem cell source consisted of UCB (n=29), PBSC (n=21), BM (n=8). Donor sources included HLA-match siblings (n=19), partially matched related (n=6), or unrelated (n=33). All pts received tacrolimus and MMF as GVHD prophylaxis (Osunkwo/Cairo et al, BBMT, 2004). CMV at risk recipients received ganciclovir/foscarnet (Shereck/Cairo et al, PBC, 2006) and all received antifungal prophylaxis with liposomal amphotericin B until day +100. F/U 686 ± 76 d. The median time to myeloid engraftment was 16 d and incidence of primary graft failure was 17.2%. Viral infections were present in 39 pts (67%) after a mean of 131 ± 104 d. CMV reactivation 10%, adenovirus 17%, RSV 17%, influenza (A and B) 10%, parainfluenza II and III 10%, BKV 17%, JCV 3%, HSV-1 12%, VZV 7%, HHV-6 1.7%, and Calicivirus 1.7%. Two pts died, 1of CMV pneumonitis and 1 of RSV pneumonia. Fungal infections were reported in 12 pts (20%) after a mean of 204 ± 188 d. Six pts had invasive fungal infection (aspergillus 2). Incidence of mortality secondary to viral and fungal infections was 5 and 17%, respectively. GVHD and its treatment with steroids were present in 43% and 50% of patients with viral and invasive fungal infections, respectively. The estimate 1 yr OS for all pts was 65% (CI: 52-78) and for malignant and non-malignant pts were 62% (CI: 47-78) and 73% (CI: 50-96), respectively. In summary, these results suggest that RI conditioning probably does not decrease the incidence of systemic viral and invasive fungal infections, likely secondary to GVHD, particularly following unrelated HLA disparity donor allografts.