New Orleans, LA—For the treatment of leukemia and other hematologic malignancies, the pool of donors for hematopoietic stem-cell transplant can be greatly expanded through the use of HLA-haploidentical, or half-matched, donors, according to researchers who reported good outcomes at ASH 2013.
With allogeneic bone marrow transplant (BMT), finding a suitable donor can be a challenge. Only 25% of siblings will be an HLA-match, and HLA matches among the pool of unrelated donors are rare. Time is also a factor in coordinating a transplant from an unrelated donor. When a fully HLA-matched donor is not available, transplants of haploidentical hematopoietic stem cells can be effective, the studies presented at ASH suggest.
“Almost every patient has at least 1 haploidentical relative, but until recently, haploBMT carried excessive risks,” said Yvette L. Kasamon, MD, Associate Professor of Oncology and Medicine, Johns Hopkins University, one of the pioneering centers for haploidentical transplants.
The primary risks include disease recurrence and the development of graft-versus-host disease (GVHD), but the studies reported at ASH found these risks to be minimal.
Laurence J. N. Cooper, MD, Associate Director, Center for Cancer Immunology Research, M.D. Anderson Cancer Center, Houston, TX, who moderated the press conference where the studies were described, said these approaches “move the technology forward.”
Haploidentical transplant, Dr Cooper said, “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.”
Posttransplant Cyclophosphamide Safe and Effective in the Elderly Dr Kasamon and colleagues demonstrated that advanced age need not be a prohibiting factor in haploidentical transplantation.
“We found no apparent decrement in overall outcomes in patients aged 60 and older or even 70 to 75 compared to those in their 50s,” Dr Kasamon said. “Since many elderly patients may lack a suitable matched sib donor, the haplo option becomes even more attractive.”
She said at a press briefing that, in most cases, Johns Hopkins no longer searches for a matched unrelated donor for patients with a relative who is a potential haploid donor.
The study was a retrospective review of 273 patients aged 50 to 75 years who received a nonmyeloablative regimen and haploBMT with posttransplant high-dose cyclophosphamide plus drugs for GVHD prophylaxis. This resulted in a low rate of acute GVHD, a low rate of chronic GVHD, a 1-year relapse rate of 37%, and a 6-month nonrelapse mortality rate of 11%.
“These results underscore that a reduced-intensity, related haploidentical transplant should be considered a very reasonable treatment option for suitable patients, up to at least age 75, who require a transplant,” she said.
Improvements in Outcomes Through Graft Manipulation
European investigators described a means of making haploidentical transplants safer and more effective through the removal of cells that are most likely to trigger donor cells to attack recipient cells, leading to GVHD, while retaining cells that will be protective.
“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 cells and gamma-delta–positive T-cells in the graft, which help prevent relapse and protect against infection,” said Alice Bertaina, MD, of the IRCCS Bambino Gesù Children’s Hospital, Rome, Italy.
Their study included 50 children 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.
Over 36 months, the cumulative incidence of transplant-related mortality was only 4%, the relapse rate was just 19%, and the leukemia-free survival rate was 77%, rising to 80% in the subset with acute lymphoblastic leukemia. The incidence of acute GVHD was 26%, and no child developed gut or liver acute disease.
“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,” Dr Bertaina said. “These results open another avenue, and show that it can actually be advantageous to choose a haploidentical relative.”