Dr. Shaw presents her talk “A Stem Cell Donor
for Every Patient.”
As a transfusionist, around Christmas and major holidays I pester my hospital blood bank staff to see if we have enough group “O” red blood cells (RBCs) to serve our patients. O cells lack “A” and “B” antigens on the RBC surface and serve as the “universal donor” for red cell transfusion. Given this, O blood group donors are in high demand with blood banks keen to have them donate blood products for patients in need. After attending the Presidential Symposium on Universal Donor Solutions in Hematology, I learned that the concept of obtaining and developing “universal” donors is very much an area of active research investigation in all of hematology, and a highly relevant and fast-evolving topic.
In many areas of hematology, life-saving critical treatments like the one highlighted above depend on removing blood cells or their precursors from one person and then reinfusing them back into a patient. Infusion of unaltered products can carry risks with serious, sometimes fatal consequences. Manipulating products to make them acceptable for infusion can be expensive (running into the hundreds of thousands of dollars) due to complex and tedious manipulations that need to be performed to make the product fit for use. Thus, achieving the holy grail of designing the “universal donor” will likely have a profound impact on the practice of hematology for both malignant and nonmalignant diseases and will make therapies available to more patients than we are currently able to treat. In this exciting session chaired by ASH President Dr. Stephanie Lee, three speakers covered broad areas of hematology including cellular immunotherapy, hematopoietic cell transplantation, and RBCs/platelet production for transfusion.
Recent advances in the area of cellular immunotherapy have been staggering, beginning with the U.S. Food and Drug Administration approval of the first chimeric antigen receptor T-cell treatment in 2017, which was followed by multiple additional approvals and an expanding list of cellular immunotherapies undergoing trials. As an apheresis practitioner, I see firsthand the challenges of obtaining cells for manipulation and downstream processing. This often involves subjecting sick patients to a several-hour procedure (apheresis) to obtain enough cells to be able to expand and manipulate them ex vivo. Because each blood product is produced from a single patient, there is tremendous variability in the types of immune cells that are harvested and inconsistency in their ability to control the tumor after infusion. There are also logistical challenges and high costs associated with manufacturing new products for every treatment. In this context, Dr. Gay Crooks discussed a wide range of highly innovative approaches to cellular immunotherapy, including gene editing and stem cell engineering; these efforts are focused on the next phase in this fast evolving field: the production of universal, off-the-shelf cellular immunotherapies with consistent potency that will be rapidly available and effective for all patients. Off-the-shelf products also provide other key potential advantages as patients are often too sick with fast-progressing diseases to undergo apheresis procedures or wait the weeks it takes to generate the immunotherapy product. I really enjoyed this fast-paced talk that, to me, resembled in many ways an engrossing science-fiction story!
Allogeneic hematopoietic stem cell transplantation (HSCT) is a life-saving treatment modality for patients with many serious malignant and nonmalignant hematologic conditions. Finding an appropriately compatible donor for the HSCT graft can be a challenge, especially for patients belonging to ethnic minority groups as demonstrated in multiple studies. Dr. Bronwen Shaw from the Medical College of Wisconsin provided a great perspective to this problem and discussed many recent innovations that have significantly expanded our ability to identify a donor for every patient requiring allogeneic HSCT. The speaker delved into details of a multipronged approach to address this issue. After attending the talk, I realized that advances in graft-versus-host disease prophylaxis, novel pre-transplant conditioning approaches, enhancements in tissue typing (HLA) technologies, and increases in donor availability help address a number of barriers to access for this therapy. It was an eye opener to appreciate the complexity of systems in place when attempting to find a donor for every patient in need of one.
Dr. Stella Chou from the University of Pennsylvania discussed the progress and challenges of generating induced pluripotent stem cell (iPSC)-derived universal platelet and red cell products. As a platelet researcher and a transfusionist, I was glued to the screen as Dr. Chou described the progress made in our ability to differentiate these iPSCs to make viable functional platelets and RBCs. How amazing would it be if one could make RBCs lacking antigens to which a patient with sickle cell disease has antibodies, or being able to make “designer” platelets lacking certain antigens that are normally hard to obtain, or unique manufactured red cells/platelets that one could use as reagents in diagnostic testing? Dr. Chou’s talk touched on these interesting issues and more. She also provided a great update on the state of the technology used to manufacture clinically relevant numbers of cells while also maintaining the same functionality that we would expect in a blood donor–derived product so that these products are efficacious. All-in-all, this was a fantastic symposium that I think predicts where hematology will be in the next decade!
Dr. Padmanabhan indicated no relevant conflicts of interest.
