Bone Marrow Transplant Regimen Achieves High Survival Rates in Patients With SCD

Nonmyeloablative haploidentical bone marrow transplant with thiotepa and post-transplant cyclophosphamide is a readily available curative therapy for most adult patients with sickle cell disease (SCD), according to a recent study.

The international, multicenter, phase II study was led by Adetola Kassim, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, and published in Blood.

A total of 70 patients (median age, 19.1) were included in the study. Using the Kaplan-Meier method, the two-year event-free survival was estimated to be 82.6% (95% CI, 71.4%-89.7%). The two-year overall survival was 94.1% (95% CI, 84.9%-97.7%), with no differences between child and adult patients (P=0.889).

Graft failure occurred in eight patients (11.4%) and only in those younger than 18 years old (P=0.001). The one-year grade 3-4 acute graft-versus-host disease (GVHD) rate, and the two-year moderate-severe chronic GVHD rate, were both 10.0% (95% CI, 4.6-18.6%). Five patients (7.1%) died from infectious complications.

Patients with engraftment had median whole blood donor chimerism values at D+180 and D+365 of 100.0% (IQR 99.8-100.0%; n=59) and 100.0% (IQR 100.0-100.0%; n=58), respectively. Fifty-seven of 59 patients (96.6%) were off immunosuppression at one year after transplant.

“We demonstrate that nonmyeloablative haploidentical [bone marrow transplant] with thiotepa and [post-transplant cyclophosphamide] is a readily available curative therapy for most adults, even those with organ damage, instead of the more expensive myeloablative gene therapy and gene editing,” the researchers concluded. “Additional strategies are required for children to decrease graft failure rates.”

Reference

Kassim A, de la Fuente J, Nur E, et al. An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease. 2024. Blood. doi.org/10.1182/blood.2023023301