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Post-Transplant Events

The influence of cyclosporin alone, or cyclosporin and methotrexate, on the incidence of mixed haematopoietic chimaerism following allogeneic sibling bone marrow transplantation for severe aplastic anaemia

Abstract

We previously reported a randomized trial comparing Cyclosporin-A (CsA) and short-term methotrexate versus CsA alone for graft-versus-host disease (GvHD) prophylaxis in 71 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) from a human leucocyte antigen-identical sibling for severe aplastic anaemia (SAA). We found a better survival in the group receiving the two-drug prophylaxis regimen with no significant difference in the probability of developing GvHD between the two groups. The present study details chimaeric analysis and its influence on survival and GvHD occurrence in 45 of the original 71 patients in whom serial samples were available. Analysis was carried out in a blinded prospective manner. Seventy-two per cent achieved complete donor chimaerism (DC), 11% stable mixed chimaerism (SMC) and 17% progressive mixed chimaerism (PMC). The overall 5-year survival probability was 82% (±11%) with a significant survival advantage (P=0.0009) in DC or SMC compared to those with PMC. Chronic GvHD was more frequent in DC patients, whereas no patient with SMC developed chronic GvHD. Graft failure occurred in 50% of the PMC group. This study demonstrates the relevance of chimaerism analysis in patients receiving HSCT for SAA and confirms the occurrence of mixed chimaerism in a significant proportion of recipients.

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Acknowledgements

We acknowledge the help of Professor Anne Dickinson, University of Newcastle upon Tyne and funding from the EU Marie Curie Research Training Network TRANSNET Contract Number: MRTN-CT-2004-512253 and the EU Concerted Action EUROCHIMERISM Contract Number: QLG1-ST-2002-01485.

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Correspondence to S McCann.

Appendix

Appendix

GITMO-EBMT participating centres

Arcese W, Institute of Hematology, La Sapienza University, Rome, Italy. Bacigalupo A, Divison of Hematology II, Ospedale S Martino, Genoa, Italy. Dini G, Instituto Giannini Gaslini, Genoa, Italy. Di Bartolmeo P, Unita Terapia Intesiva Ematologica per il Trapianto Emopoietico, Dimpatimento di Ematologia, Ospedale Civile, Pescara, Italy. Falta M, Locatelli F, Division of Hematology, Ospedale Molinette, Turin, Italy. Iacopino P, Divisioin of Hematology, Az. Osp. Biachi-Melacrino-Morelli, Reggio Calabria, Italy. Izzi T, Department of Medicien, Spedali Civili, Brescia, Italy. Locasciulli A, Pediatric Clinic, Osp. Nuovo S Gerardo, University of Milano, Monza, Italy. Locatelli F, Pediatric Clinic, IRCCS Pol. S Matteo Pavia, Italy. McCann S, Lawler M, Department of Hematology, St James's Hospital, Trinity College, Dublin, Ireland.

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McCann, S., Passweg, J., Bacigalupo, A. et al. The influence of cyclosporin alone, or cyclosporin and methotrexate, on the incidence of mixed haematopoietic chimaerism following allogeneic sibling bone marrow transplantation for severe aplastic anaemia. Bone Marrow Transplant 39, 109–114 (2007). https://doi.org/10.1038/sj.bmt.1705552

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