Progress in GVHD management improves efficacy of allogeneic HSCT

The use of allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia has come “a long way in the past 5 to 10 years,” according to Jonathan M. Gerber, MD, of the Carolinas HealthCare System’s Levine Cancer Institute.

Graft-versus-host disease (GVHD) — which is “the major complication” associated with allogeneic HSCT for the treatment of leukemia — has decreased with the use of several strategies and appears to be the primary way in which the use of allogeneic HSCT has been improved. In one recent trial, prophylactic treatment with low-dose corticosteroids hastened platelet recovery and reduced the prevalence of acute GVHD among high-risk patients undergoing haploidentical HSCT. Another study demonstrated that the use of adult umbilical cord blood transplantation resulted in decreased rates of chronic GVHD compared with peripheral blood transplants from matched, unrelated donors. Cord blood transplantation was also shown to decrease the burden of immunosuppression and the occurrence of late complications.

Jonathan Gerber

In addition, expanding to alterative donor pools — particularly with haploidentical donors — has helped to reduce GVHD. This approach includes utilization of posttransplant cyclophosphamide, according to Gerber, a HemOnc Today editorial board member. While haploidentical transplantation followed by posttransplant cyclophosphamide has demonstrated survival outcomes comparable with matched unrelated donor transplantation in patients with AML, patients with haploidentical matched donors had a lower risk for GVHD.

“We now have ways to mitigate GVHD and, thus, reduce one of the most feared side effects of that treatment,” Gerber said.

The use of checkpoint inhibitors in AML may further enhance the benefits of allogeneic HSCT, although research in this area is still in the preliminary stage, according to Gerber. A recent investigation in The New England Journal of Medicine found that ipilimumab (Yervoy, Bristol-Myers Squibb), a monoclonal antibody that blocks CTLA-4, induced complete responses among patients with hematologic malignancies who relapsed after allogeneic HSCT. Responses appeared durable for several histologic subtypes, including extramedullary AML, although the researchers noted the occurrence of immune-mediated toxic effects and GVHD.

“These are early trials, but it will be interesting to see if we can utilize some of these immune-based therapies, including checkpoint inhibitors, to perhaps harness the benefits of allogeneic HSCT without all of the potential risks of that intensive therapy,” he said.

Taken together, these developments mean that allogeneic HSCT is “now far safer than it used to be,” Gerber said.

“It will be interesting to see how each of these therapies work together and, in particular, help to identify those patients in whom we need to escalate therapy as opposed to those who may have been cured by less intensive measures.” – by Julia Ernst, MS

Disclosures: Gerber reports an advisory role with Seattle Genetics.