Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood

Dana-Farber Cancer Institute, Boston, MA, USA.
Blood (Impact Factor: 10.45). 04/2011; 117(25):6963-70. DOI: 10.1182/blood-2011-01-332007
Source: PubMed


The success of reduced intensity conditioning (RIC) transplantation is largely dependent on alloimmune effects. It is critical to determine whether immune modulation with anti-T-cell antibody infusion abrogates the therapeutic benefits of transplantation. We examined 1676 adults undergoing RIC transplantation for hematologic malignancies. All patients received alkylating agent plus fludarabine; 792 received allografts from a human leukocyte antigen-matched sibling, 884 from a 7 or 8 of 8 HLA-matched unrelated donor. Using Cox regression, outcomes after in vivo T-cell depletion (n = 584 antithymocyte globulin [ATG]; n = 213 alemtuzumab) were compared with T cell- replete (n = 879) transplantation. Grade 2 to 4 acute GVHD was lower with alemtuzumab compared with ATG or T cell- replete regimens (19% vs 38% vs 40%, P < .0001) and chronic GVHD, lower with alemtuzumab, and ATG regimens compared with T-replete approaches (24% vs 40% vs 52%, P < .0001). However, relapse was more frequent with alemtuzumab and ATG compared with T cell-replete regimens (49%, 51%, and 38%, respectively, P < .001). Disease-free survival was lower with alemtuzumab and ATG compared with T cell-replete regimens (30%, 25%, and 39%, respectively, P < .001). Corresponding probabilities of overall survival were 50%, 38%, and 46% (P = .008). These data suggest adopting a cautious approach to routine use of in vivo T-cell depletion with RIC regimens.

Download full-text


Available from: Edmund K Waller, Dec 02, 2014
  • Source
    • "Previous studies in patients with hematologic malignancies also found similar TRM, relapse, and OS between UD myeloablative HSCT after rabbit ATG (Thymoglobulin) and MRD HSCT [25], [26], [30]. However, a recent retrospective analysis with data from the Center for International Blood and Marrow Transplant Research (CIBMTR) found that ATG conditioning in reduced-intensity HSCT increased the likelihood of relapse, which negatively influenced disease-free survival in patients with hematologic malignancies [31]. Therefore, immune modulation with ATG in the reduced-intensity setting might abrogate the graft-versus-leukemia effect that is responsible for the elimination of residual malignant cells that persist after a less intensive preparative regimen. "
    [Show abstract] [Hide abstract]
    ABSTRACT: One of the major drawbacks for unrelated donor (UD) bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Despite results from randomized trials, antithymocyte globulin (ATG) is not routinely included for GVHD prophylaxis in UD BMT by many centers. One of ways to demonstrate the usefulness of rabbit ATG in UD BMT is to evaluate how its results approximate to those observed in matched related (MRD) BMT. Therefore, we compared the outcomes between UD BMT with rabbit ATG (Thymoglobulin) for GVHD prophylaxis (n = 25) and MRD BMT (n = 91) for leukemia and myelodysplasia. All but one patient received a myeloablative conditioning regimen. Grades II-IV acute GVHD were similar (39.5% vs. 36%, p = 0.83); however, MRD BMT recipients developed more moderate-severe chronic GVHD (36.5% vs. 8.6%, p = 0.01) and GVHD-related deaths (32.5% vs. 5.6%, p = 0.04). UD BMT independently protected against chronic GVHD (hazard ratio 0.23, p = 0.04). The 6-month transplant-related mortality, 1-year relapse incidence, and 5-year survival rates were similar between patients with non-advanced disease in the MRD and UD BMT groups, 13.8% vs. 16.6% (p = 0.50), 20.8% vs. 16.6% (p = 0.37), and 57% vs. 50% (p = 0.67), respectively. Stable full donor chimerism was equally achieved (71.3% vs. 71.4%, p = 1). Incorporation of rabbit ATG in UD BMT promotes less GVHD, without jeopardizing chimerism evolution, and may attain similar survival outcomes as MRD BMT for leukemia and myelodysplasia especially in patients without advanced disease.
    PLoS ONE 09/2014; 9(9):e107155. DOI:10.1371/journal.pone.0107155 · 3.23 Impact Factor
  • Source

    Blood 06/2011; 117(23):6061-2. DOI:10.1182/blood-2011-04-348409 · 10.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been more than 50 years since Professor George Mathe explored the use of non-specific immunotherapy to treat secondary disease after allogeneic transplantation.
    Blood 06/2011; 117(25):6744-5. DOI:10.1182/blood-2011-05-348433 · 10.45 Impact Factor
Show more