Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation for Patients With Aplastic Anemia

Summary

Rationale: Chemotherapy with fludarabine, cyclophosphamide and anti-thymocyte globulin may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, depletion CD3±CD19 cells may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation. Purpose: This phase I/II trial is to evaluate the safety and efficacy of fludarabine, cyclophosphamide and antithymocyte globulin with CD3±CD19 depleted graft from haploidentical donors in treating patients with aplastic anemia.

Timeline

Start

2009-07

Primary completion

2012-07

Completion

2012-07

Publications

• Background Woodard P, Cunningham JM, Benaim E, Chen X, Hale G, Horwitz E, Houston J, Kasow K, Leung W, Wang W, Yusuf U, Handgretinger R. Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia. Bone Marrow Transplant. 2004 Feb;33(4):411-8. doi: 10.1038/sj.bmt.1704358.
• Background Kremens B, Basu O, Grosse-Wilde H, Sauerwein W, Schaefer UW, Havers W. Transplantation of CD34-enriched peripheral stem cells from an HLA-haplotype mismatched donor to a patient with severe aplastic anemia. Bone Marrow Transplant. 2001 Jan;27(1):111-3. doi: 10.1038/sj.bmt.1702748.
• Background Lacerda JF, Martins C, Carmo JA, Lourenco F, Juncal C, Ismail S, Lacerda JM. Haploidentical stem cell transplantation with purified CD34+ cells after a chemotherapy-alone conditioning regimen in heavily transfused severe aplastic anemia. Biol Blood Marrow Transplant. 2005 May;11(5):399-400. doi: 10.1016/j.bbmt.2005.02.007. No abstract available.
• Background Klingebiel T, Cornish J, Labopin M, Locatelli F, Darbyshire P, Handgretinger R, Balduzzi A, Owoc-Lempach J, Fagioli F, Or R, Peters C, Aversa F, Polge E, Dini G, Rocha V; Pediatric Diseases and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT). Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group. Blood. 2010 Apr 29;115(17):3437-46. doi: 10.1182/blood-2009-03-207001. Epub 2009 Dec 29.
• Results Koh KN, Im HJ, Kim BE, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Haploidentical haematopoietic stem cell transplantation using CD3 or CD3/CD19 depletion and conditioning with fludarabine, cyclophosphamide and antithymocyte globulin for acquired severe aplastic anaemia. Br J Haematol. 2012 Apr;157(1):139-42. doi: 10.1111/j.1365-2141.2011.08924.x. Epub 2011 Nov 5. No abstract available.
• Im HJ, Koh KN, Suh JK, Lee SW, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Refinement of treatment strategies in ex vivo T-cell-depleted haploidentical SCT for pediatric patients. Bone Marrow Transplant. 2015 Feb;50(2):225-31. doi: 10.1038/bmt.2014.232. Epub 2014 Oct 13.

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