ALBERT

Description: Reduced intensity conditioning for allogeneic hematopoietic cell transplantation (alloHCT) has become a standard approach for older patients and for those with co-morbidities that prohibit myeloablative conditioning. The optimal conditioning regimen for patients with AML or MDS undergoing such transplants is not clear. Therefore we performed a single center, retrospective analysis comparing busulfan (100 mg/m2/day on days -5, -4, -3, -2) and fludarabine (40 mg/m2/day on days -5, -4, -3, -2) (BuFlu) versus fludarabine (30 m2/day on days -5, -4, -3) and 400 cGy total body irradiation (200 cGy on days -1 and 0) (FluTBI) conditioning. All of the BuFlu transplants were performed as inpatient hospitalizations while all of those with FluTBI were performed as an outpatient. A total of 71 patients in two cohorts were included. The first study cohort consisted of 38 patients (23 AML, 15 MDS) who received FluTBI from 3/2004-4/2010, and the second included 33 (20 AML, 13 MDS) patients conditioned with FluBu from 6/2010-12/2013. The groups had similar disease risk and HCT comorbidity index scores. The BuFlu patients were older (median age 65 [range, 34-73] vs. 61[range, 44-70] years, P=0.03), but there were no other differences in patient or disease characteristics. All patients received peripheral blood stem cells as the graft source. The donor sources were 53% matched related (MRD) and 47% matched unrelated (MUD) for FluTBI patients and 58% MRD and 42% MUD for BuFlu patients. The BuFlu group received more red blood cell (RBC) transfusions (median 4 vs. 2, P=0.02), but there were no differences in platelet transfusion requirements. Platelet recovery was longer for patients receiving BuFlu than FluTBI (median 16 vs. 12 days, P=0.004), but there was no difference in cumulative incidence of neutrophil recovery. The respective median number of days hospitalized in the first 100 days post-transplant was 22 vs. 10 days (P

Description: Background Cytomegalovirus (CMV) is a common infectious complication after allogeneic hematopoietic cell transplantation (alloHCT). Efforts to enhance immune reconstitution post-transplant have been pursued to help facilitate clearance of such infections. Assessment of natural killer (NK) cell allo-reactivity with investigation of killer cell immunoglobulin-like receptors has been reported to be associated with protection from CMV infection after alloHCT (Davis ZB et al, BBMT 2015). In addition, the activating NKG2D receptor controls immune responses by regulating NK cells, NKT cells and γδ-T cells. MHC class I chain-related gene A (MICA) is a polymorphic ligand of the NKG2D receptor on these immune effector cells. Given the potential benefit of NK cell allo-reactivity for protection from CMV infection after alloHCT we hypothesized that MICA polymorphisms may influence CMV infection rates after such transplants. Methods We conducted a single center, retrospective analysis of allogeneic HCTs for adults with hematologic malignancies in which MICA data were available for donors and recipients. Analysis was restricted to patients with T-cell replete HLA-8/8 matched related or unrelated donor. Fine and Gray regression was used to identify risk factors for CMV infection. The first episode of graft-versus-host-disease (GVHD) was analyzed relative to CMV as a time-dependent covariate. An analysis was performed examining dimorphisms at the MICA-129 position, which previously has been categorized as weaker (valine/valine: V/V), heterozygous (methionine/valine: M/V), or stronger (methionine/methionine: M/M) receptor binding affinity. Results From 2000-2016, 423 alloHCT patients were identified who had MICA data. Diagnoses included 197 AML, 82 MDS, 34 ALL, 34 NHL, 22 CML, 12 CMML, 9 CLL, 9 myelofibrosis, 9 plasma cell myeloma, 9 other leukemias, and 6 Hodgkin lymphoma. High, intermediate, and low co-morbidity index was seen in 42%, 33%, and 25% of patients, respectively. Median age at transplant was 52 years (range, 18-76), with 95% Caucasian. A myeloablative transplant was performed in 80% of patients and 52% had a bone marrow graft source. CMV infection occurred in 141 (33%) of patients at a median time of 46 days post-transplant (range, 0-609 days) with 29 (21%) occurring within 30 days, 108 (77%) within 100 days and 33 (23%) after day 100. Thirty-three (8%) patients were MICA mismatched with their donor. Donor MICA-129 dimorphisms included 203 (48%) V/V, 190 (45%) M/V and 30 (7%) M/M. Baseline donor(d)/recipient(r) CMV serostatus for V/V vs. M/V + M/M cohorts were 25% vs. 28% for d+/r+, 11% vs 9% for d+/r-, 39% vs. 37% for d-/r+, and 25% vs. 26% for d-/r- (P=0.75). In univariate analysis, MICA mismatch was associated with a higher risk of CMV (HR 1.64, CI 1.00-2.69, P=0.049), and V/V donor MICA-129 dimorphism with a marginally higher risk of CMV (HR 1.32, CI 0.85-1.83, P=0.10). In multivariable analysis, MICA mismatch was not associated with CMV infection (HR 1.38, CI 0.83-2.29, P=0.22) while V/V donor MICA-129 dimorphism was associated (HR 1.40, CI 1.00-1.96, P=0.05) (Figure 1). Other significant variables in multivariable analysis were year of transplant (HR 0.95, CI 0.92-0.99 P=0.01), non-Caucasian race (HR 2.15, CI 1.18-3.91, P=0.01), high-risk disease (HR 1.62, CI 1.13-2.32 P=0.008), baseline CMV serostatus (HR 7.51, CI 3.76-15.0, P