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<p>Myeloablative HLA-matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for children with sickle cell disease (SCD), achieving survival rates over 90%. However, optimal conditioning for older SCD patients undergoing MRD transplantation is unknown. We evaluated a novel conditioning regimen comprising thymoglobulin, thiotepa, cyclophosphamide, fludarabine, and total-body irradiation (200 cGy). Graft-versus-host disease (GVHD) prophylaxis included post-transplant cyclophosphamide (100 mg/kg), mycophenolate mofetil, and sirolimus. We aimed to improve donor engraftment rates, decrease GVHD, and minimize toxicity. A total of 25 patients were prospectively recruited in a multicentre study across three sites; 22/25 (88%) were fully matched, and 3/25 (12%) received a one-antigen-mismatched sibling transplant. 12% (3/25) of patients had experienced a second graft failure from a previous HCT. 11 participants (44%) received bone marrow, while 14 (56%) received peripheral blood as stem cell sources. The median age was 26.7 years (IQR, 18.53–32.02), and the median follow-up was 42 months (IQR, 30-49). The estimated 5-year event-free survival rate was 96%, and the 2-year overall survival rate was 100%. No graft failure was observed. Median whole blood chimerism at day +28 and day +365 engraftment was 100% and 97%, respectively. Among evaluable participants, 17/21 (81%) were off immunosuppression at 1-year post-transplant. The 1-year grade III-IV acute GVHD rate was 4% (<i>n</i> = 1), with no chronic GVHD. This regimen produced high engraftment and survival in this cohort using our novel conditioning regimen for MRD HSCT in adolescents and adults with severe SCD, including those undergoing a second HSCT. Optimal donor engraftment is associated with a lower risk of secondary myeloid neoplasms.</p><p></p>

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Excellent outcomes using a novel reduced intensity conditioning with thiotepa and post-transplant cyclophosphamide for HLA-matched related donor transplant in adolescents and adults with sickle cell disease

  • 期刊论文

  • 发表日期：

    2026年4月28日

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  • Reem Alasbali,
  • Mohsen Alzahrani,
  • Karina Wilkerson,
  • Phavina Akhom,
  • Fahad Alotaibi,
  • Bader Alahmari,
  • Josu de la Fuente,
  • Michael R. DeBaun,
  • Walid Rasheed,
  • Hadeel Samarkandi,
  • Riad El Fakih,
  • Mostafa Saleh,
  • Tusneem Elhassan,
  • Hazza Alzahrani,
  • Mahmoud Aljurf,
  • Fahad Almohareb,
  • Adetola A. Kassim,
  • Ali AlAhmari

摘要

Myeloablative HLA-matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for children with sickle cell disease (SCD), achieving survival rates over 90%. However, optimal conditioning for older SCD patients undergoing MRD transplantation is unknown. We evaluated a novel conditioning regimen comprising thymoglobulin, thiotepa, cyclophosphamide, fludarabine, and total-body irradiation (200 cGy). Graft-versus-host disease (GVHD) prophylaxis included post-transplant cyclophosphamide (100 mg/kg), mycophenolate mofetil, and sirolimus. We aimed to improve donor engraftment rates, decrease GVHD, and minimize toxicity. A total of 25 patients were prospectively recruited in a multicentre study across three sites; 22/25 (88%) were fully matched, and 3/25 (12%) received a one-antigen-mismatched sibling transplant. 12% (3/25) of patients had experienced a second graft failure from a previous HCT. 11 participants (44%) received bone marrow, while 14 (56%) received peripheral blood as stem cell sources. The median age was 26.7 years (IQR, 18.53–32.02), and the median follow-up was 42 months (IQR, 30-49). The estimated 5-year event-free survival rate was 96%, and the 2-year overall survival rate was 100%. No graft failure was observed. Median whole blood chimerism at day +28 and day +365 engraftment was 100% and 97%, respectively. Among evaluable participants, 17/21 (81%) were off immunosuppression at 1-year post-transplant. The 1-year grade III-IV acute GVHD rate was 4% (n = 1), with no chronic GVHD. This regimen produced high engraftment and survival in this cohort using our novel conditioning regimen for MRD HSCT in adolescents and adults with severe SCD, including those undergoing a second HSCT. Optimal donor engraftment is associated with a lower risk of secondary myeloid neoplasms.