Hematopoietic Stem Cell Transplantation for Severe Thalassemia Patients from Haploidentical Donors Using a Novel Conditioning Regimen.

Abstract

Patients with severe thalassemia commonly have a survival that is significantly shorter than that of the general population. Allogeneic hematopoietic stem cell transplantation (allo-SCT) is the only established treatment that is potentially curative, but it is limited by the availability of donors and the medical condition of the patient. To expand the donor pool to include haploidentical related donors, we introduced a program consisting of a pharmacologic pretransplant immune suppression phase (PTIS) and 2 courses of dexamethasone and fludarabine, followed by pretransplant conditioning with fludarabine-i.v. busulfan and post-transplant graft-versus-host disease (GVHD) prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil. We transplanted 83 consecutive transfusion-dependent patients with thalassemia (median age, 12 years; range, 1 to 28 years) with a minimum follow-up of 6 months (median, 15 months; range, 7 to 53 months); the 3-year projected overall and event-free survival is over 96%, and there have been no secondary graft failures. Of the first 31 patients, we had 2 graft failures, both of them occurring in patients with extremely high titers of anti-donor-specific HLA antibodies (anti-DSAs), but after adjusting the PTIS to include bortezomib and rituximab for patients with high titers of anti-DSAs and using pharmacologic dose guidance for busulfan, we had no graft failures in the last 52 patients. Six (7%) of 83 patients developed severe GVHD. We conclude that this is a safe and efficacious approach to allogeneic SCT in thalassemia, yielding results comparable to those available for patients with fully matched donors.

• Authors: Usanarat Anurathapan, Suradej Hongeng, Samart Pakakasama, Duantida Songdej, Nongnuch Sirachainan, Pongpak Pongphitcha, Ampaiwan Chuansumrit, Pimlak Charoenkwan, Arunee Jetsrisuparb, Kleebsabai Sanpakit, Piya Rujkijyanont, Arunotai Meekaewkunchorn, Yujinda Lektrakul, Pornchanok Iamsirirak, Pacharapan Surapolchai, Somtawin Sirireung, Rosarin Sruamsiri, Pustika Amalia Wahidiyat, Borje S Andersson
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 26 Issue 6 Pg. 1106-1112 (06 2020) ISSN: 1523-6536 [Electronic] United States
• PMID: 31931116 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020. Published by Elsevier Inc.

Chemical References

• Busulfan

Topics

• Busulfan (therapeutic use)
• Child
• Graft vs Host Disease (prevention & control)
• Hematopoietic Stem Cell Transplantation
• Humans
• Thalassemia (therapy)
• Transplantation Conditioning