Graft Manipulation Improves HLA-Haploidentical Hematopoietic Stem Cell Transplant Outcomes
T-cell–depleted HLA-haploidentical hematopoietic stem cell transplantation can be made more efficacious and safer through the removal of alpha/beta-positive T cells and CD19-positive B cells from the graft, an approach pioneered by Italian investigators who reported results at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 157).
First author Alice Bertaina, MD, of the Bambino Gesu Children’s Hospital in Rome, noted that when a fully matched donor is not available to leukemia patients, transplants of haploidentical, or half-matched, hematopoietic stem cells can be effective but are associated with an increased risk of disease recurrence and graft-vs-host disease, compared to a fully matched donor transplant. In the study presented at ASH, researchers selectively removed those cells that are most likely to trigger donor cells to attack recipient cells, in an effort to make these transplants safer and more effective.
“We recently developed a new method of graft manipulation based on the physical removal of alpha/beta-positive T cells and CD19-positive B cells, which permits us to leave mature natural killer (NK) cells and gamma/delta-positive T cells in the graft,” she said at a press conference. NK and gamma/delta-positive T cells help prevent relapse and protect against infection.
“The selective graft manipulation results in effective prevention of both acute and chronic graft-vs-host disease, rapid recovery of neutrophil and platelet counts, and low transplant-related mortality,” she said. “Although the median observation time is still limited, the cumulative incidence of disease recurrence is encouraging.”
Study Outcomes
Dr. Bertaina and colleagues used this approach in 50 children (median age, 10 years) with acute lymphoblastic or acute myeloid leukemia with a parent serving as the haploidentical donor. The donor’s blood was filtered through a column where magnetic microbeads captured and separated the T cells to be retained from those slated for elimination. Patients underwent a myeloablative regimen, with or without total-body irradiation, and received antithymocyte globulin and rituximab (Rituxan).
Over 36 months, the cumulative incidence of transplant-related mortality was only 4% and the relapse rate was just 19%. The Kaplan-Meier estimate of leukemia-free survival was 77%, rising to 80% in the subset with acute lymphoblastic leukemia. The incidence of acute graft-vs-host disease was 26%, and no child developed gut or liver acute disease. Only two patients developed skin-limited chronic graft-vs-host disease, she reported.
Sustained primary engraftment occurred in all patients, and median time to reach an absolute neutrophil count > 0.5×109/L and platelet count > 50×109/L was 13 days and 11 days, respectively.
Dr. Bertaina predicted that using this approach to improving the safety and efficacy of haploidentical transplants, more patients will receive transplants and fewer will die during the procurement of an unrelated donor.
“Until now, we have searched for unrelated volunteer donors, but it is difficult to propose to the parents that we must wait for this search, before we treat,” she said. “These results open another avenue, and show that it can actually be advantageous to choose a haploidentical relative.”
Donor May Be ‘In the Same Room’
Laurence Cooper, MD, of The University of Texas MD Anderson Cancer Center, Houston, who moderated the press conference where the study was described, said the approach “moves the technology forward in terms of efficacy.”
“First, with this new stem cell modification technology, we can pull out just the stem cells we want, leaving the graft intact,” he said. “The second advantage is that this shortens the time to finding the donor. We don’t have to pull potential donors from a massive registry. We will often find a donor in the same room as the patient.”
The study authors reported no potential conflicts of interest.
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