Although pretransplant alemtuzumab can reduce GVHD following allogeneic transplantation, it may also increase the risk of mixed donor T-cell chimerism and infections. We hypothesized that the early use of DLI without withdrawal of immunosuppressive drugs in patients with mixed T-cell chimerism would lower the risk of relapse without significantly increasing the risk of GVHD post DLI. Thirty-six patients (median age 59 years) were treated in this phase II trial using reduced-intensity conditioning including s.c. alemtuzumab (total dose 43 mg) and a PBSC graft from a matched unrelated donor (UD). DLI without withdrawal of immunosuppressive drugs was administered to all 25 patients with o50% donor T-cell chimerism on day þ 60. The cumulative risks of acute and chronic GVHD were 42% and 59%, respectively. Estimated probabilities of non-relapse mortality (NRM) at day 100 and 1 year were 3% and 14%, respectively. With a median follow up 2.4 years, estimated survivals at day 100, 1 and 2 years were 97%, 71% and 57%, respectively. In multivariate analysis, the occurrence of acute GVHD was associated with an increased risk of mortality, whereas the occurrence of chronic GVHD had a protective effect, associated with decreased relapse and improved disease-free survival. Low-dose alemtuzumab and preemptive DLI provides favorable transplant outcomes including low NRM in an older patient population with high-risk malignancies undergoing UD transplantation.

Relapse remains a major cause of mortality among patients receiving allogeneic hematopoietic cell transplantation (HCT). The impact of donor type on post-relapse survival (PRS) has not been widely examined. We compared the survival outcomes for patients relapsing after haploidentical donor transplantation (HIDT) using post-transplant cyclophosphamide with those relapsing after matched-related donor transplantation (MRDT) or matched-unrelated donor transplantation (MUDT) at our institution. Two hundred and thirty-seven consecutive HCT recipients with relapse occurring after HIDT (N = 48), MUDT (N = 87) and MRDT (N = 102) were included in this analysis. Median age was 49 years (19-77 years) and the median time to relapse was 156 days (12-2465) after HCT. HIDT recipients had similar median time to relapse (5.8 vs 4.8 vs 5.5 months, P = 0.638) compared with MUDT and MRDT, respectively. One-year PRS was worse among HIDT recipients compared with MRDT and MUDT (17% vs 46% vs 40%, P o 0.05). In a multivariate analysis, time to relapse ( o3 vs 43 months post transplant), no use of donor lymphocyte infusion (DLI) following relapse, higher Dana Farber disease risk index and HCT comorbidity index scores at the time of transplant and delayed platelet engraftment post transplant were all predictive of worse PRS. This analysis shows that 1-year PRS is inferior among HIDT when compared with MRDT or MUDT. Lower use of DLI after HIDT may have contributed to this inferior survival. INTRODUCTIONAllogeneic hematopoietic cell transplantation (HCT) is considered to be a curative modality for many patients with high-risk hematologic malignancies. Transplantation using a matchedrelated sibling if available leads to improved outcomes when compared with other graft sources. 1 HLA-haploidentical donor transplantation (HIDT) using a T-cell-replete graft with posttransplant cyclophosphamide has emerged as an alternative graft source for patients lacking a matched-related (MRD) or matchedunrelated (MUD) donor. [2][3][4][5] The use of HIDT with post-transplant cyclophosphamide has been shown to yield low rates of transplant-related mortality, adequate disease control, robust immune reconstitution and overall survival (OS) similar to that seen with optimally MUD transplantations. 2,6 Relapse remains the main cause of treatment failure after HCT with~30-40% of patients relapse with their original malignancy. 7 Outcomes after relapse after HCT remain poor with a high early mortality and only a small percentage of patients achieving a long-term second remission and prolonged OS. The effect of graft donor source at the time of transplantation on post-relapse survival (PRS) has not been well established. In a recent CIBMTR (Center for International Blood and Marrow Transplantation Research) analysis, patients with relapsed acute myelogeneous leukemia after mismatchedunrelated or double cord transplantation had a worse PRS than recipients of a matched sibling or matched-unrelated HCT. 8 The available treatment options for relapsed patients include i...

Inadequate T-cell chimerism following reduced-intensity conditioning transplantation may contribute to graft rejection and disease relapse. Anti-thymocyte globulin (ATG) enhances early donor T-cell chimerism, but may also deplete donor T cells, increasing risks of infection and relapse. We prospectively tested administration of rabbit ATG (rATG) ⩾ 14 days before the infusion of the graft, followed by in vivo decay of active rATG levels, to selectively deplete host T cells. Twenty-three patients received rATG total dose 4.5 mg/kg on days − 16 and − 15, fludarabine 30 mg/m 2 per day on day − 7 through − 3, IV busulfan 130 mg/m 2 per day on days − 4 and − 3 and cyclophosphamide 1500 mg/m 2 on day − 2. rATG levels were therapeutic in all patients on day − 14, but were sub-therapeutic (o 1 μg/mL) by day 0 in 82% of patients. Median donor T-cell chimerisms on days 30 and 180 were 100% (75-100%) and 100% (90-100%), respectively. Non-relapse mortality and relapse/progression at 48 months were 17 and 30%. Cumulative incidences of acute GvHD grades II-IV and III-IV were 39 and 9%. Median follow-up is 64 months (46-79 months). Survival and disease-free survival at 48 months were 70 and 52%. These data suggest that selective depletion of host T cells using this regimen is a feasible and effective strategy.