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Saturday, June 2, 2018

Clinical Challenges for Stem Cell Transplants: Selecting the Right Donor

By Christina Bennett

Stem cell transplants can be problematic in hematologic malignancies, such as acute myeloid leukemia, because adverse events like graft versus host disease can develop and survival time can become shortened. For patients with chronic lymphocytic leukemia, a range of therapies are available depending on a person's age, disease risk group, and other factors, but allogeneic hematopoietic stem cell transplantation is the only potentially curative treatment available at this time.

At the 2018 ASCO Annual Meeting, Marcos J.G. De Lima, MD, Director of Hematologic Malignancies and Stem Cell Transplant Program at University Hospitals Seidman Cancer Center, gave a presentation about selecting a less than perfect matched donor for patients with hematologic malignancies who need a stem cell transplant. There are three stem cell transplant donor options: mismatched unrelated, haploidentical, or cord blood donors. During the presentation, Lima noted several trends in donor selection.

"There is this huge drive for haploidentical transplants. Outside the United States, unrelated donor transplants are disappearing," he said, citing several studies for this trend (Bone Marrow Transplantation 2017;52:811-817; Blood Advances 2017;1:397-400.). "Cord blood transplants are disappearing because of the financial aspects of the transplant. Again, I'm not claiming that this is better or worse yet; however, this is what's happening."

He went on to elaborate on this trend.

"Why would haploidentical transplants become so strong?" he asked. He explained that it's financially sound to do a haploidentical stem cell transplant because it's a family affair. In contrast, just the procurement of a cord blood or a bone marrow alone is around $50,000 he said.

Also, the speed of procurement is faster for haploidentical transplant than unrelated or cord blood transplants.

"An unrelated donor search can go anywhere from 3 months to 6 months, probably the median is around 2-3 months, and sometimes we don't have that luxury of time." Another advantage of haploidentical transplants, he said, is the relative ease in terms of doing post-transplant interventions, because the family relative is available.

Modern approaches to haploidentical transplants have developed over the past few decades and around the world. For example, in the U.S., cyclophosphamide is often given to patients after hematopoietic stem cell transplantation (Semin Hematol 2015;52:232-242). "This approach has been by far the most popular in the United States," Lima said.

He noted that the gold standard for hematopoietic stem cell transplant is still a fully matched sibling donor; when the donor pool is composed of parents, children, and siblings, a person has about a 50 percent chance of matching for a stem cell transplant. However, "families are shrinking," making that option less likely. Take, for example, in China, where families often have one child and, therefore, no fully matched siblings.

About the options for stem cell transplant donors, he said the question has long been, "Which one is the best?" He said, "Slowly people are agreeing at least to look at this question in a more rational way, but it's still somewhat irrational."

Retrospective studies have sought to answer the question of which type of stem cell donor is best, but the results have been largely inconclusive (BBMT 2014; 20:1573-1579; Blood 2011;118:282-288; J Clin Oncol 2013;31:1310-1316).

Trending toward more rational donor selection is the prospective, open-label, randomized, phase III trial BMT CTN 1101, which aims to compare the efficacy of haploidentical bone marrow transplant with double umbilical cord blood transplant in patients with leukemia or lymphoma (NCT01597778). About 400 participants are enrolled at this time. The primary endpoint is a 2-year progression-free survival and the trial is powered to detect a 15 percent difference.

"The BMT CTN is about to conclude actually. This is a major endeavor, I think, of randomization between those two approaches," he said. "So this would be an interesting study to see the results.

"In conclusion, it's very fair to say that today, most patients have a donor," he said. Though he cautioned this may not be the case for minorities, who have more genetic heterogeneity, and may have more difficulty finding an unrelated donor. In contrast, Caucasians are more homogenous genetically, so more donors exist.

"Practice is changing fast," he asserted. "At the end of the day, there may be lots of choices that are made based on local expertise. There are institutions that are just very good with cord blood, and sometimes you may argue, why would we change?"

Christina Bennett is a contributing writer.