Use of a five-agent GVHD prevention regimen in recipients of unrelated donor marrow

Abstract

Summary:A five-agent GVHD prophylaxis programme consisting of cyclosporin A, methotrexate, anti-thymocyte-globulin, pentaglobin and metronidazol was given to 48 recipients of unrelated donor marrow with chronic myelogenous leukemia, acute leukemia, myelodysplastic syndromes, and familiar lymphocytic hemophagocytosis of an average age of 33.5 (0.6-56) years. GVHD grades II-IV occurred in 18 patients (39%) and grades III-IV in five patients (11%). Chronic GVHD developed in nine patients (23%), three limited and six extensive. Fifteen patients died. Clinical relapse was detected in eight patients. Four patients died as a consequence of the underlying disease and subsequent treatment, 11 patients died of transplant-related causes. After a median follow-up of 19 months, the overall and diseasefree survival are 67% and 62%, respectively. Survival by age is as follows: 0-19 years: 12/13 patients; 20-39 years: 14/25 patients; 40-59 years: 7/10 patients. The five-agent GVHD prophylaxis regimen is effective. Matched-unrelated donor transplants can be carried out safely in patients younger than 50 years of age. The results in patients younger than 20 years of age should encourage matched-unrelated donor transplants at earlier stages of the disease.

Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation – a retrospective analysis

“…2 The antibody had been incorporated into dose-reduced conditioning regimens for two reasons: first, ATG given before transplantation exerts T-cell depletion of the recipient, which facilitates donor stem cell engraftment after nonmyeloablative doses of BU and FLU and second, antibody persisting in the recipient beyond transplantation exerts in vivo depletion of donor T cells, thereby possibly reducing the risk for acute and chronic GVHD. 3,4 However, ATG has considerable short-term toxicity. 5 While the efficacy of ATG to prevent GVHD and to reduce nonrelapse mortality after myeloablative HSCT has been demonstrated in several studies, the role of ATG in reduced-intensity conditioning has not been evaluated.…”

Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis

“…6 In recent years, a number of European centers have reported relatively low rates of acute GVHD and early TRM using a variety of ATG products and schedules of administration. [7][8][9][10][11][12][13][14][15] Total doses of pretransplant thymoglobulin have ranged between 8 and 20 mg/kg. 8,9,12,13 An IBMTR analysis of alternative donor transplants between 1987 and 1993 indicated that the influence of donors on outcome was not apparent in high risk patients but quite significant with low and intermediate risk disease.…”

“…[1][2][3][4][5][6] In addition, some uncontrolled studies have indicated that pretransplant serotherapy with antithymocyte globulin (ATG) or other antibodies appears to reduce acute GVHD and early mortality of closely matched UD BMT to levels comparable to matched related donor (MRD) BMT. [7][8][9][10][11][12][13][14][15] Since 1995 we have used a relatively low dose of rabbit ATG in the pretransplant conditioning protocol for all UD transplants. Outcomes of 57 of these patients are compared with those of 57 MRD BMT recipients matched for important prognostic factors.…”

Antithymocyte globulin for the prevention of graft-versus-host disease after unrelated hematopoietic stem cell transplantation for acute myeloid leukemia: results from the multicenter German cooperative study group

“…Several studies, however, suggest also a beneficial effect of ATG in preventing acute graft-versus-host disease (aGvHD). [4][5][6][7] The only randomized study, examining the use of ATG for the prophylaxis of GvHD published 3 years ago, suggests that ATG significantly reduces the risk for severe acute GvHD but increases the risk for infections. 8 In addition, survival was similar even though extensive chronic GvHD (cGvHD) was significantly reduced in patients receiving ATG.…”