February 2014, Vol 3, No 1
More Transplants Made Possible Through Haploidentical Donors
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 haploidentical, or half-matched, donors, according to research groups who reported studies with good outcomes at ASH.
With allogeneic bone marrow transplant (BMT), finding a suitable donor can be a challenge. Only one-quarter of siblings will be a human leukocyte antigen (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 suggest.
“Almost every patient has at least 1 haploidentical relative, but until recently, haploBMT carried excessive risks,” said Yvette L. Kasamon, MD, of Johns Hopkins University, Baltimore, MD, 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 Cooper, MD, PhD, of MD Anderson Cancer Center, Houston, TX, who moderated the press conference where the studies were described, said these approaches “move the technology forward,” which promises to expand the number of patients who can receive transplants.
Haploidentical transplant, he 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 Is Safe and Effective in the Elderly
Kasamon and colleagues demonstrated that advanced age need not be a prohibiting factor in haploidentical transplantation when patients are otherwise transplant eligible, at least when using a reduced-intensity regimen and posttransplant cyclophosphamide, which can be delivered in the outpatient setting.
“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,” 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, 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 (32% for all grades and 3% for grades 3/4), a low rate of chronic GVHD (12% at 1 year), a 1-year relapse rate of 37%, and a 6-month nonrelapse mortality rate of 11%. By age, outcomes were comparable, and nonrelapse mortality was similar, she reported.
“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,” Kasamon 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 Bambino Gesu Children’s Hospital in Rome, Italy.
“The selective graft manipulation results in effective prevention of both acute and chronic GVHD, 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.”
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% and 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.
Bertaina predicted that using this approach, 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.”
Elderly and unfit patients constitute the majority of patients with chronic lymphocytic leukemia (CLL), but unfortunately these groups have limited treatment options. A second-generation fully humanized monoclonal antibody against the CD20 protein, ofatumumab, added to chlorambucil improves clinical outcomes and is tolerable irrespective of age and fitness in patients with [ Read More ]
PROGRESS REPORT: Implementation of ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research
In November 2011, ASCO issued a prescription for transforming clinical cancer research in the United States and speeding the creation of effective new therapies for patients. In its report, Accelerating Progress Against Cancer: ASCO’s Blueprint for Transforming Clinical and Translational Cancer Research, ASCO laid out a vision for a cancer [ Read More ]