Myeloablative Conditioning With Thiotepa Improves Haploidentical HSCT in SCD

Use of an intensified myeloablative conditioning regimen containing thiotepa showed promising efficacy and acceptable safety in patients with severe sickle cell disease (SCD) undergoing haploidentical hematopoietic stem cell transplantation, according to a poster presentation at the 2024 Tandem Meetings of ASTCT® and CIBMTR®.

The report, presented by Susan Kelly, MD, from AdventHealth for Children, suggested this novel preparative regimen is a valuable improvement to haploidentical transplants given that less than 20% of patients with SCD have a human leukocyte antigen-identical sibling donor available.

Thiotepa Improves Haploidentical HSCT for SCD Treatment

From 2015 to 2023, a total of 28 consecutive patients with severe SCD (SS genotype) received HSCT with the intensified conditioning regimen at two pediatric centers. The cohort had a median age of 14.4 years (range, 5.9-24.8) and was 57% male. Among the transplants, the donor was parent in 57% and sibling in 43%; 90% of donors had sickle cell trait; and the graft source was bone marrow in 80% and peripheral blood in 20%.

The exact conditioning regimen was antithymocyte globulin (0.5 mg/kg on day -9 and 0.2 mg/kg on days -8 to -7), thiotepa (10 mg/kg on day -7), fludarabine 30 mg/m² (days -6 to -2), cyclophosphamide (14.5 mg/kg on days -6 to -5), and total body irradiation (200 Gy on day -1). Graft-versus-host disease (GVHD) prophylaxis was cyclophosphamide 50 mg/kg/ on days three and four and mycophenolate mofetil starting day five.

The authors stated all patients achieved neutrophil and platelet engraftment at medians of 21.5 days (range, 15-24) and 26.5 days (range, 12-110) respectively, after HSCT. Three patients had secondary graft failure within six months of transplantation, though all three had successful engraftment and were disease free after undergoing a second transplant.

The rates of grade 3 to 4 acute GVHD and moderate-to-severe chronic GVHD were 7.1% (n=2) and 3.5% (n=1), respectively. Additionally, at a median follow-up of 2.5 years, the rates of event-free survival and overall survival were 84% and 95%, respectively.

“Our results are encouraging and support the hypothesis that intensifying the preparative regimen with the addition of myeloablative thiotepa can result in rapid and sustained full donor engraftment with acceptable toxicities and GVHD rates,” Dr. Kelly and colleagues concluded.

More: Zahra Pakbaz, MD; John Strouse, MD, PhD, Discuss Practicing Classical Hematology

Reference

Kelly S, Domm J, Carroll C, et al. Haploidentical hematopoietic stem cell transplant for patients with sickle cell disease using thiotepa, fludarabine, thymoglobulin, low dose cyclophosphamide, 200 Cgy TBI and post-transplant cyclophosphamide. Abstract #409. Presented at the 2024 Tandem Transplantation & Cellular Therapy Meetings of ASTCT® and CIBMTR®; February 21-24, 2024; San Antonio, Texas.