On January 15-17, 2017, the 4th Worldwide Network for Blood and Marrow Transplantation Workshop was held at the King Faisal Research and Cancer Center in Rhyadh, Saudi Arabia.
Dr. Usama Gergis of the Weill Cornell Medicine and NewYork-Presbyterian Bone Marrow Transplant Program served as session chair and moderator for a symposium on the long-term complications of bone marrow transplantation.
Additionally, Dr. Gergis served as a panelist for a roundtable discussion entitled Cell Processing and HLA Typing. HLA or “human leukocyte antigen” typing refers to testing that is done to match potential marrow and stem cell donors and recipients based on a set of genes located on the short arm of chromosome 6. This matching is essential for the success of the bone marrow transplant procedure.
In this session, Dr. Gergis discussed the role of HLA antibodies in mismatched stem cell graft failure and presented the unique strategy utilized at WCM/NYP to desensitize recipients and achieve better engraftment or “uptake” of the new stem cells. This engraftment occurs when the new stem cells travel to the bone marrow and start to produce their own blood cells.
When this fails to happen, it is called “graft failure” and it is often due to the presence of donor-specific anti-HLA antibodies (DSA) that are targeted against the mismatched HLA antigens. In our program, high-resolution typing for HLA class I (-A, -B, -C,) and class II (-DRB1 -DQ and –DP) loci is therefore routinely performed for all recipients and stem cell donors. In addition, serum samples of the recipient are tested for IgG Antibodies against HLA class I and class II Antigens. We attempt to avoid graft sources that have HLA Antigens or alleles targeted by these antibodies. But in some cases all potential related or unrelated grafts are targeted by DSA. For such cases we developed a strategy to decrease the DSA burden before allogeneic transplantation.
The desensitization started 4–6 weeks before transplant and involved using combinations of intravenous immunoglobulins (IVIG) and the plasma cell targeted medication, bortezomib. This strategy is effective in decreasing the antibodies in most patients, which resulted in durable stem cell engraftment in high-risk patients who harbored these antibodies.