An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease

• Published in: Blood Vol. 143; no. 25; pp. 2654 - 2665
• Main Authors: Kassim, Adetola A., de la Fuente, Josu, Nur, Erfan, Wilkerson, Karina L., Alahmari, Ali D., Seber, Adriana, Bonfim, Carmem, Simões, Belinda Pinto, Alzahrani, Mohsen, Eckrich, Michael J., Horn, Biljana, Hanna, Rabi, Dhedin, Nathalie, Rangarajan, Hemalatha G., Gouveia, Roseane Vasconcelos, Almohareb, Fahad, Aljurf, Mahmoud, Essa, Mohammed, Alahmari, Bader, Gatwood, Katie, Connelly, James A., Dovern, Elisabeth, Rodeghier, Mark, DeBaun, Michael R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-06-2024
• Subjects: Adolescent; Adult; Anemia, Sickle Cell - therapy; Bone Marrow Transplantation - adverse effects; Bone Marrow Transplantation - methods; Child; Child, Preschool; Cyclophosphamide - administration & dosage; Cyclophosphamide - therapeutic use; Female; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Humans; Male; Middle Aged; Thiotepa - administration & dosage; Thiotepa - therapeutic use; Transplantation Conditioning - methods; Transplantation, Haploidentical - methods; Young Adult
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2023023301

•For most adults with sickle cell disease, haploidentical BMT with thiotepa + PTCy is now a widely available curative option with excellent outcomes.•For children, haploidentical BMT with thiotepa + PTCy requires additional strategies to decrease graft failure rates.
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In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative–related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.4%) and only in participants aged <18 years; all had autologous reconstitution. After a median follow-up of 2.4 years, the 2-year Kaplan-Meier–based probability of event-free survival was 82.6%. The 2-year overall survival was 94.1%, with no difference between children and adult participants. After excluding participants with graft failure (n = 8), participants with engraftment had median whole blood donor chimerism values at days +180 and +365 after transplant of 100% (n = 58), respectively, and 96.6% (57/59) were off immunosuppression 1 year after transplant. The 1-year grade 3 to 4 acute graft-versus-host disease (GVHD) rate was 10%, and the 2-year moderate–severe chronic GVHD rate was 10%. Five participants (7.1%) died from infectious complications. We demonstrate that nonmyeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, compared to the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates. The trial was registered at www.clinicaltrials.gov as #NCT01850108.
In this month’s CME article, Kassim and colleagues report results of an international phase 2 trial of haploidentical bone marrow transplant for 70 patients with sickle cell disease (SCD) using thiotepa in conditioning and posttransplant cyclophosphamide. Outcomes were excellent, with a 2-year overall survival of 94%. Graft failure was seen in 11% of patients, all in patients aged under 18 years. This provides an attractive and more affordable alternative to gene therapy, which is not feasible for a wide swath of patients with SCD.