Discussion of BMT CTN 1507 (Kassim AA et al., NEJM Evidence 2025): a phase 2, single-arm, multicenter (19 US centers) study of haploidentical bone marrow transplantation in adults aged 15 to 45 years with severe sickle cell disease. Reduced-intensity conditioning used thymoglobulin, thiotepa, fludarabine, cyclophosphamide, and 200 cGy TBI, with hydroxyurea for 60 days prior; GVHD prophylaxis was post-transplant cyclophosphamide, mycophenolate, and sirolimus for one year. Of 54 included, 42 underwent transplantation. With a median follow-up of 37.2 months, the 2-year event-free survival was 88% and the overall survival was 95%. Graft failure was 7.1% (all with autologous reconstitution), acute GVHD grade 3 was 4.8% (no grade 4), and chronic GVHD was 22.4%.

There were two deaths in the first year, both due to viral infection (HHV-6 and SARS-CoV-2); 62% had some infection and 79% were readmitted. Painful crises requiring hospitalization fell from 24% to zero after engraftment.

Haplo with thiotepa or 400 cGy TBI? Does hydroxyurea before transplantation help? What is the price in infection and chronic GVHD for a benign disease? And what can be done in Brazil, where gene therapy is not available? We compared it with the Vanderbilt collaborative (episode 41) and the Johns Hopkins series.


Article: https://doi.org/10.1056/EVIDoa2400192

Presentation: Maria Fernanda Dezan
Discussion: Gabriele Ritter, Karine Vicenzi, Rafael Faust, Luiza Pires, and Vinícius Molla

Chapters:
00:00 Introduction
00:17 Article Presentation
21:09 Discussion

See also:
▶️ Episode 41 — Haplo-TMO in sickle cell anemia: the Vanderbilt collaborative: 41 - Phase 2 trial for haploidentical bone...