MANNOSE-BINDING LECTIN STATUS IS ASSOCIATED WITH RISK OF MAJOR INFECTION FOLLOWING MYELOABLATIVE SIBLING ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION Short title: MBL status and infection following allo-HCT

Mannose-binding lectin (MBL) is a mediator of innate immunity that influences the risk of infection in a range of clinical settings. We previously reported associations between MBL2 genotype and infection in a retrospective study of myeloablative allogeneic hematopoietic stem cell transplantation. However, other studies have been inconclusive, and the role of MBL in reduced intensity conditioning (RIC) transplants is unknown. Here we report a prospective study examining MBL2 genotype, MBL levels and risk of major infection following HLA-matched sibling myeloablative (N=83) and RIC (n=59) HCT. Baseline MBL levels were higher in recipients than donors (P<0.0001), and recipient MBL levels increased during the peri-transplant period (P=0.0002), most notably in MBL2 wild-type individuals receiving myeloablative total body irradiation (mTBI). MBL2 coding mutations were associated with major infection in recipients receiving mTBI. The cumulative incidence of major infection in recipient harboring an MBL2 mutation receiving mTBI was 70.6%, compared with 31.1% of those without mutations not receiving mTBI. (P=0.01). MBL status was not associated with infection in RIC transplants. These results confirm the association of MBL status with risk of infection in myeloablative, TBI-conditioned transplants. Studies examining the role of MBL replacement therapy to prevent infection in this setting should be considered. For personal use only. by guest on June 2, 2013. bloodjournal.hematologylibrary.org From