Haploidentical HSCT graft manipulation prevented GVHD, improved survival in pediatric leukemia

NEW ORLEANS — Removing alpha- and beta-positive T cells and CD19-postive B cells from the donor graft reduced the risk for graft-versus-host disease and transplant-related mortality in children with acute leukemia undergoing HLA-haploidentical hematopoietic stem cell transplantation, according to study results presented at the ASH Annual Meeting and Exposition.

Alice Bertaina, MD, of the IRCCS Bambino Gesù Children’s Hospital in Rome, Italy, and colleagues manipulated donor grafts by removing the alpha- and beta-positive T cells and CD19-postiive B cells, leaving mature natural killer and gamma- and delta-positive T cells.

They evaluated this approach in 50 pediatric patients with leukemia. The median age of patients was 10.2 years (range, 0.9-17.9) and 32 of the patients were boys.

Thirty-eight of the patients had acute lymphoblastic leukemia (ALL) and twelve had acute myeloid leukemia (AML).

Median follow-up was 18 months (range, 6-36).

All patients but one engrafted. The patient who experienced secondary graft failure was successfully retransplanted from the other relative.

The median time to reach an absolute neutrophil count ˃0.5x10⁹/L was 13 days (range, 9-18), and the median time to reach a platelet count ˃50x10⁹/L was 11 days (range, 8-20).

Researchers noted that none of the patients developed gut or liver acute GVHD.

Thirteen patients experienced skin-only grade 1 to grade 2 GVHD (29%; 95% CI, 18-45). Two patients developed skin-limited chronic GVHD.

The cumulative incidence of transplant-related mortality was 4% (95% CI, 1-16).

Nine patients relapsed, equating to a 19% (95% CI, 6-32) cumulative incidence of disease recurrence.

The 2-year estimate for leukemia-free survival was 77% (95% CI, 57-86). For patients with ALL, the estimate for 2-year leukemia-free survival was 79% (95% CI, 52-85).

Leukemia-free survival of patients who did experience skin-only acute GVHD was 85% (95% CI, 48-96), compared with 74% (95% CI, 50-86) in patients who did not.

Researchers noted the appearance of mature natural killer cells in the peripheral blood 1 month after HSCT.

“Our results, which demonstrate that transplantation of selectively modified, half-matched donor stem cells boasts success rates equivalent to those of a fully matched transplant, preventing GVHD and reducing transplant-related death, help continue to establish this approach as a viable option for patients without a matched donor,” Bertaina said in a press release. “This has the potential to make this lifesaving treatment more accessible to a much larger population of patients who may not have a perfect donor match.”

 

For more information:

Bertaina A. Abstract #157. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2013; New Orleans.

 

Disclosure: The researchers report no relevant financial disclosures.