Antithymocyte globulin before allogeneic stem cell transplantation for progressive myelodysplastic syndrome : a study from the French Society of Bone Marrow Transplantation and Cellular Therapy
[en] We investigated the impact of rabbit antithymocyte globulins (ATG) on patient outcomes after allogeneic stem cell transplantation (allo-SCT) for progressive myelodysplastic syndrome (MDS). Of the 242 consecutive patients who underwent allo-SCT for progressive MDS between October 1999 and December 2009, 93 received ATG (ATG group) at the median dose of 5 mg/kg, whereas 149 patients did not (no-ATG group). Donors were sibling (n ¼ 153) or HLA-matched unrelated (n ¼ 89). Patients received blood (n ¼ 90) or marrow (n ¼ 152) grafts after either myeloablative (n ¼ 109) or reduced-intensity (n ¼ 133) conditioning. Three-year overall and event-free survival, nonrelapse mortality, relapse, and chronic graft-versus-host disease (GVHD) development were not significantly different between the 2 groups. In contrast, acute grade II to IV GVHD occurred more
often in the no-ATG group (55% of the patients) than in the ATG group (27%, P < .0001). Similar results were observed with acute grade III to IV GVHD (28% and 14% in the no-ATG group and ATG group, respectively; P ¼ .009). In multivariate analysis, after adjustment with propensity score, the absence of ATG was the strongest parameter associated with an increased risk of acute grade II to IV GVHD (hazard ratio, 2.13; 95% confidence interval, 1.35 to 3.37; P ¼.001]. ATG had no impact on overall and event-free survival or cumulative incidence of the relapse. In conclusion, the addition of ATG to allo-SCT conditioning did not increase the incidence of relapse of patients with progressive MDS. The incidence of acute GVHD was decreased without compromising outcomes.
Disciplines :
Hématologie
Auteur, co-auteur :
Duléry, Rémy
Mohty, Mohamad
Duhamel, Alain
Robin, Marie
BEGUIN, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Antithymocyte globulin before allogeneic stem cell transplantation for progressive myelodysplastic syndrome : a study from the French Society of Bone Marrow Transplantation and Cellular Therapy
Kröger N., Bornhäuser M., Ehninger G., et al. Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Ann Hematol 2003, 82:336-342. 10.1007/s00277-003-0654-9.
Andersson B.S., Valdez B.C., de Lima M., et al. Clofarabine ± fludarabine with once daily i.v. busulfan as pretransplant conditioning therapy for advanced myeloid leukemia and MDS. Biol Blood Marrow Transplant 2011, 17:893-900. 10.1016/j.bbmt.2010.09.022.
Depil S., Deconinck E., Milpied N., et al. Donor lymphocyte infusion to treat relapse after allogeneic bone marrow transplantation for myelodysplastic syndrome. Bone Marrow Transplant 2004, 33:531-534. 10.1038/sj.bmt.1704381.
Oliansky D.M., Antin J.H., Bennett J.M., et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of myelodysplastic syndromes: an evidence-based review. Biol Blood Marrow Transplant 2009, 15:137-172. 10.1016/j.bbmt.2008.12.003.
Yakoub-Agha I., de La Salmonière P., Ribaud P., et al. Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation. JClin Oncol 2000, 18:963-971.
Cheson B.D., Greenberg P.L., Bennett J.M., et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006, 108:419-425. 10.1182/blood-2005-10-4149.
Petersdorf E.W., Hansen J.A. New advances in hematopoietic cell transplantation. Curr Opin Hematol 2008, 15:549-554. 10.1097/MOH.0b013e328311891f.
Cahn J.-Y., Klein J.P., Lee S.J., et al. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: a joint Société Française deGreffe de Moëlle et Thérapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study. Blood 2005, 106:1495-1500. 10.1182/blood-2004-11-4557.
Champlin R.E., Ho W.G., Mitsuyasu R., et al. Graft failure and leukemia relapse following T lymphocyte-depleted bone marrow transplants: effect of intensification of immunosuppressive conditioning. Transplant Proc 1987, 19(1 Pt 3):2616-2619.
Marmont A.M., Horowitz M.M., Gale R.P., et al. T-cell depletion of HLA-identical transplants in leukemia. Blood 1991, 78:2120-2130.
Mohty M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia 2007, 21:1387-1394. 10.1038/sj.leu.2404683.
Mohty M., Labopin M., Balère M.L., et al. Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire. Leukemia 2010, 24:1867-1874. 10.1038/leu.2010.200.
Finke J., Bethge W.A., Schmoor C., et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol 2009, 10:855-864. 10.1016/S1470-2045(09)70225-6.
Bacigalupo A., Lamparelli T., Barisione G., et al. Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant 2006, 12:560-565. 10.1016/j.bbmt.2005.12.034.
Blaise D., Tabrizi R., Boher J.-M., et al. Randomized study of 2 reduced-intensity conditioning strategies for human leukocyte antigen-matched, related allogeneic peripheral blood stem cell transplantation: prospective clinical and socioeconomic evaluation. Cancer 2013, 119:602-611. 10.1002/cncr.27786.
Kröger N., Zabelina T., Krüger W., et al. Invivo T cell depletion with pretransplant anti-thymocyte globulin reduces graft-versus-host disease without increasing relapse in good risk myeloid leukemia patients after stem cell transplantation from matched related donors. Bone Marrow Transplant 2002, 29:683-689. 10.1038/sj.bmt.1703530.
Socie G., Schmoor C., Bethge W.A., et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood 2011, 117:6375-6382. 10.1182/blood-2011-01-329821.
Wolschke C., Zabelina T., Ayuk F., et al. Effective prevention of GVHD using invivo T-cell depletion with anti-lymphocyte globulin in HLA-identical or -mismatched sibling peripheral blood stem cell transplantation. Bone Marrow Transplant 2014, 49:126-130. 10.1038/bmt.2013.143.
Bonifazi F., Bandini G., Stanzani M., et al. Invivo T-cell depletion with low-dose ATG is effective in reducing cGVHD after peripheral blood stem cell myeloablative sibling transplants in CML: results from a prospective phase II study. Bone Marrow Transplant 2005, 35:1025-1026. 10.1038/sj.bmt.1704940.
Soiffer R.J., Lerademacher J., Ho V., et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood 2011, 117:6963-6970. 10.1182/blood-2011-01-332007.
De Masson A., Beylot-Barry M., Bouaziz J.-D., et al. Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas. Haematologica 2013 Nov 8, [Epub ahead of print]. 10.3324/haematol.2013.098145.
Bennett J.M., Catovsky D., Daniel M.T., et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 1976, 33:451-458.
Gupta G., Singh R., Kotasthane D.S., Kotasthane V.D. Myelodysplastic syndromes/neoplasms: recent classification system based on World Health Organization Classification of Tumors - International Agency for Research on Cancer for Hematopoietic and Lymphoid Tissues. JBlood Med 2010, 1:171-182. 10.2147/JBM.S12257.
Greenberg P., Cox C., LeBeau M.M., et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997, 89:2079-2088.
Cheson B.D., Bennett J.M., Kantarjian H., et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 2000, 96:3671-3674.
Bay J.-O., Dalle J.-H., Dhedin N., et al. Prophylaxie de la réaction aiguë du greffon contre l'hÔte. Hématologie 2011, 17:15-17.
Kalbfleisch J.D., Prentice R.L. The statistical analysis of failure time data 2011, John Wiley & Sons, New York.
Fine J., Gray R.J. Aproportional hazards model for the subdistribution of a competing risk. JAm Stat Assoc 1999, 94:496-509.
D'Agostino R.B. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 1998, 17:2265-2281.
Lee S.J., Klein J., Haagenson M., et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 2007, 110:4576-4583. 10.1182/blood-2007-06-097386.
Yakoub-Agha I., Mesnil F., Kuentz M., et al. Allogeneic marrow stem-cell transplantation from human leukocyte antigen-identical siblings versus human leukocyte antigen-allelic-matched unrelated donors (10/10) in patients with standard-risk hematologic malignancy: a prospective study from the French Society of Bone Marrow Transplantation and Cell Therapy. JClin Oncol 2006, 24:5695-5702. 10.1200/JCO.2006.08.0952.
Martino R., Valcárcel D., Brunet S., et al. Comparable non-relapse mortality and survival after HLA-identical sibling blood stem cell transplantation with reduced or conventional-intensity preparative regimens for high-risk myelodysplasia or acute myeloid leukemia in first remission. Bone Marrow Transplant 2008, 41:33-38. 10.1038/sj.bmt.1705879.
Blaise D., Kuentz M., Fortanier C., et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle. JClin Oncol 2000, 18:537-546.
Schmitz N., Beksac M., Hasenclever D., et al. Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukemia. Blood 2002, 100:761-767. 10.1182/blood-2001-12-0304.
Mohty M., Bay J.-O., Faucher C., et al. Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen. Blood 2003, 102:470-476. 10.1182/blood-2002-12-3629.
Waller E.K., Langston A.A., Lonial S., et al. Pharmacokinetics and pharmacodynamics of anti-thymocyte globulin in recipients of partially HLA-matched blood hematopoietic progenitor cell transplantation. Biol Blood Marrow Transplant 2003, 9:460-471.
