By Basem M. William, MD

One of the major leaps in hematopoietic stem cell transplantation (HSCT) is the increasingly successful use of alternative donors, thereby allowing the delivery of a potentially curative transplant to approximately 75 percent of patients who do not have an HLA-matched sibling donor. Overall, only 30 percent of patients have a matched-related do- nor. While 60 percent of Caucasians have an HLA- matched unrelated donor in the registry, this is the case for only 21 percent of African Americans. The development of both haploidentical transplants (haplo-HSCT) and umbilical cord blood (UCB) transplants occurred in parallel depending on institutional experience and preferences.

The development of post-transplant cyclophosphamide (PTCY) by the investigators at Johns Hopkins University has revolutionized haplo-HSCT and made them easy to perform with a risk of graft-versus-host disease (GVHD) that appears comparable to, or even lower than, matched donor transplants according to the latest registry studies. UCB remains expensive, however, with favorable outcomes in institutions experienced in performing them. In the Education Program session titled, Spoiled for Choice: Donor Selection for Allogeneic Stem Cell Transplantation, Leo Luznik, MD, of Johns Hopkins University, discussed the increasing role of haplo-HSCT the use of PTCY, and the unique biology and strategies for treatment of relapse after haplo-HSCT. Subsequently Annalisa Ruggeri, MD, of Hospital Saint Antoine in Paris, discussed the strategy for selection of optimal UCB units for transplantation, impact of conditioning and GVHD prophylaxis regimens, current strategies in clinical trials to improve UCB transplants in children and adults, the emerging field of ex vivo expansion of UCB cells, and studies comparing outcomes of transplants from UCB and other graft sources. Katharina Fleischauer, MD, of University Hospital Essen in Essen, Germany, covered strategies for optimizing the selection of un- related donors from national donor registries, dis- cussing the importance of HLA-matching, impact of donor age, role of extended typing of HLA-DPB1 locus, and how PTCY can help extend transplant beyond “HLA barriers.”

As Dr. Fleischauer indicated, “We should change the way we think about matching …we are seeing a major paradigm shift because of use of PTCY.” The emerging role of HLA loss as a mechanism that cancer cells use to escape the immune system after trans- plantation was also discussed, as well as how this may influence how disease relapse post-transplantation is treated. HLA loss may be more relevant in haplo-HSCT as compared to cord blood, as the speakers shared with me; however, these data are preliminary, and further studies are needed for validation.

Another related session in the Education Program (repeated Monday at 7:00 a.m.) discusses Why Patients Fail After Allogeneic Stem Cell Transplantation. Luca Vago, MD, PhD, of the San Raffaele Scientific Institute in Italy, presented the different immune, and non-immune, escape mechanisms that tumor cells employ to escape graft-versus-leukemia (GVL) effect. Subsequently, Jacqueline Cloos, PhD, of Cancer Center Amsterdam discussed various methods for minimal residual disease (MRD) monitoring, followed by Smita Bhatia, MD, MPH, of University of Alabama at Birmingham, who spoke about late mortality after HSCT not related to relapse, including secondary malignancies; chronic GVHD; infections; cardiopulmonary late effects; metabolic syndrome; and how to quantitate the risk of, appropriately monitor, and pre-emptively manage, such complications.

The quest goes on to promote the “Dr. Jekyll” of HSCT (cure of hematologic malignancies through GVL) rather than the “Mr. Hyde,” in Dr. Fleischauer words (GVHD, infections, conditioning regimen toxicity, and late metabolic and cardiovascular effects) and positively affect patient lives after HSCT.

Dr. William indicated no relevant conflicts of interest.

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