Azathioprine/hydroxyurea preconditioning prior to nonmyeloablative matched sibling donor hematopoietic stem cell transplantation in adults with sickle cell disease: A prospective observational cohort study.

Autor: Dovern E; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Aydin M; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Hazenberg MD; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Tang MW; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Suijk EM; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Hoogendoorn GM; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Van Tuijn CFJ; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Kerkhoffs JL; Department of Hematology, HagaZiekenhuis, The Hague, The Netherlands., Rutten CE; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Zeerleder SS; Department of Hematology, Division of Internal Medicine, Luzerner Kantonsspital, Lucerne, Switzerland., de la Fuente J; Department of Paediatrics, St. Mary's Hospital, Imperial Healthcare NHS Trust, London, UK.; Department of Immunology and Inflammation, Imperial College London, London, UK., Biemond BJ; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Nur E; Department of Hematology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2024 Aug; Vol. 99 (8), pp. 1523-1531. Date of Electronic Publication: 2024 May 11.
DOI: 10.1002/ajh.27360
Abstrakt: Nonmyeloablative, matched sibling donor hematopoietic stem cell transplantation with alemtuzumab/total body irradiation (TBI) conditioning is a curative therapy with low toxicity for adults with sickle cell disease (SCD). However, relatively low donor chimerism levels and graft rejection remain important challenges. We hypothesized that adding azathioprine/hydroxyurea preconditioning will improve donor chimerism levels and reduce graft failure rate. In this prospective cohort study, we enrolled consecutive adult patients with SCD undergoing matched sibling donor transplantation at the Amsterdam UMC. Patients received azathioprine 150 mg/day and hydroxyurea 25 mg/kg/day for 3 months prior to alemtuzumab 1 mg/kg and 300 cGy TBI conditioning. Twenty patients with SCD (median age 26 years [range 19-49], 13 females) were transplanted. Median follow-up was 46.0 months (IQR 21.8-57.9). One-year overall survival and event-free survival (graft failure or death) were both 95% (95% confidence interval 86-100). Mean donor myeloid and T-cell chimerism 1-year post-transplant were 95.2% (SD ±10.6) and 67.3% (±15.3), respectively. One patient (5%) experienced graft failure without autologous regeneration, resulting in infections and death. All other patients had a corrected SCD phenotype and were able to discontinue sirolimus. Three patients were successfully treated with alemtuzumab (1 mg/kg) after the transplant because of declining donor chimerism and cytopenias to revert impending graft rejection. Toxicity was mostly related to sirolimus and alemtuzumab. One patient developed steroid-responsive grade II intestinal acute graft-versus-host disease. Collectively, preconditioning with azathioprine/hydroxyurea prior to nonmyeloablative matched sibling donor transplantation resulted in excellent event-free survival and robust donor T-cell chimerism, enabling the successful withdrawal of sirolimus. ClinicalTrials.gov: NCT05249452.
(© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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