Low Dose Subcutaneous Alemtuzumab and Prophylactic Donor Lymphocyte Infusion Results in Favorable Outcomes for High Risk Recipients of Unrelated Donor Allogeneic Transplants.

Abstract

Abstract 2272Poster Board II-249Non-relapse mortality (NRM) remains a major obstacle to success of unrelated donor (UD) allogeneic transplantation, mostly due to the increased morbidity from graft-versus-host disease (GVHD). Unfortunately, efforts to reduce GVHD mortality with ex vivo or in vivo T cell depletion techniques have often been associated with increased risk of relapse and infectious complications. We hypothesized that pre-transplant low-dose Alemtuzumab would reduce early NRM following UD transplantation, coupled with the early use of donor lymphocyte infusion (DLI) to correct incomplete donor chimerism (DC) to improve disease control. We targeted a high risk patient population (age>40 years or prior transplant) to test this hypothesis. Twenty-seven patients (median age 56 years) received PBSC (n=25) or BM (n=2) allografts from matched (n=25) or one-antigen mismatched (n=2) unrelated donors for high-risk hematologic malignancies (CIBMTR disease risk high [n=14], intermediate [n=6], low [n=7]). Conditioning included Fludarabine and Busulfan (myeloid) or Cyclophosphamide ± Rituximab (lymphoid). Subcutaneous Alemtuzumab was administered at a dose of 43mg over 3 days, day -11, -10, and -9. Twenty-six patients (96%) achieved sustained engraftment. With a median follow-up of 1.6 years, the estimated 2-year overall survival is 73.5%. NRM at 100 days and 2 years is 0% and 4.2%, respectively. Twenty-two patients received early prophylactic DLI for incomplete DC, while 7 received ≥2 DLI. Risk of Grade II-IV and III-IV acute GVHD is estimated to be 48% and 11%, respectively, with chronic GVHD occurring in 78%. Relapse/progression was documented in 41.9% of patients with current disease-free survival (DFS) estimated to be 65.2%. Compared to contemporaneously treated UD transplant recipients not receiving pre-transplant Alemtuzumab, study patients demonstrated delayed achievement of complete DC (median 148 vs. 61 days, p=0.002), delayed acute GVHD onset (median 113 vs. 30 days, p=001), and increased requirement for DLI (81% vs. 10%, p<0.001). Overall rates of acute and chronic GVHD were similar. Despite being a decade older in age (median 56 vs. 44 years), study patients had comparable outcomes with a non-significant trend to lower 2-year NRM (4.2 vs. 21.5%) and higher current DFS (65.2 vs. 46.8%) (see figure). Low dose subcutaneous Alemtuzumab with prophylactic DLI results in favorable transplant outcomes and modest rates of NRM in an older patient population with high-risk hematologic malignancies receiving UD transplantation. [Display omitted] Disclosures:Off Label Use: Alemtuzumab is being used off-label as part of the preparative regimen for unrelated donor allogeneic transplantation..