1. Hematopoietic Stem Cell Transplantation for Severe Thalassemia Patients from Haploidentical Donors Using a Novel Conditioning Regimen.
- Author
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Anurathapan, Usanarat, Hongeng, Suradej, Pakakasama, Samart, Songdej, Duantida, Sirachainan, Nongnuch, Pongphitcha, Pongpak, Chuansumrit, Ampaiwan, Charoenkwan, Pimlak, Jetsrisuparb, Arunee, Sanpakit, Kleebsabai, Rujkijyanont, Piya, Meekaewkunchorn, Arunotai, Lektrakul, Yujinda, Iamsirirak, Pornchanok, Surapolchai, Pacharapan, Sirireung, Somtawin, Sruamsiri, Rosarin, Wahidiyat, Pustika Amalia, and Andersson, Borje S.
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BUSULFAN , *HEMATOPOIETIC stem cell transplantation , *ALEMTUZUMAB , *RITUXIMAB , *THALASSEMIA , *TOTAL body irradiation , *STEM cell transplantation , *GRAFT rejection - Abstract
• Allogeneic stem cell transplant (SCT) is curative for patients with severe thalassemia. It can be safely performed with a sequence of a pretransplant immunosuppressive therapy (PTIS) of pulse fludarabine and dexamethasone, followed by a reduced-intensity regimen of fludarabine and i.v. busulfan, as well as peripheral blood progenitor transplant with post-transplant cyclophosphamide-based immunosuppression. • Patients with very high titers of anti-donor-specific antibodies (1:3000) further benefited from the addition of bortezomib and Rituxan to the PTIS phase to alleviate antibody-mediated graft rejection. • With this approach, SCT now be safely carried out using both matched and mismatched (aka haploidentical) donors, with a 3-year event-free and overall survival of 95%, regardless of donor type, and without having any increased risk for mortality in patients who are older than 7 years and having hepatomegaly (i.e., the Lucarelli group III high-risk subset). • This demonstrates that there is no reason to take the risk(s) of total body irradiation to secure engraftment in this group of patients who are at high risk for graft failure. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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