Once Deemed ‘Incompatible’ Donor Stem Cells Cure

Sickle cells disease is an inherited blood disorder which primarily affects the black community. New protocols allow stem cells from family members if half of their human leukocyte antigen markers match for patients with aggressive sickle cell disease. Prior to changes donors had to be family members with full set of matching human leukocyte antigen markers or a fully matched donor.

Human leukocyte antigen markers are proteins on cell surfaces that help to regulate the immune system, which are used to identify what cells belong in the body from those that don’t. Family members are most likely to have matching proteins, as markers are inherited from parents. Matching markers in regards to transplants between patients and donors help limit risk of rejection.

Finding donors who are closely matched is always a priority for doctors searching for donor matches for patients requiring stem cell transplants, but unfortunately only about 20% of patients will have a family member with a full set of matching markers. Progress has been made in curing adults with this disease using stem cell transplants, until now the majority of these patients have not been able to benefit from this treatment because of lack of matching compatible donors. Allowing for half matched donors in the new protocol, which uses only a small dose chemotherapy, numbers of potential donors for patients have increased significantly, which is great news.

50 adult sickle cell patients were screened as candidates for the new protocol of half matched transplant markers, 10 of which received stem cell transplants. Following 2 unsuccessful transplants the new protocol treatment was adopted including modifications first developed at Johns Hopkins University. Modifications included increasing dose of radiation used before transplant, and infusing growth factor mobilized peripheral blood stem cells instead of bone marrow cells; both of which helped to ensure patient body would accept healthy donor cells.

The 8 remaining patients underwent revised transplants. One of which experienced chronic graft-versus-host disease and died from unknown causes. The 7 other patients are all alive, maintaining 95% or greater stable engraftment acceptance of transplanted donor cells, with improved blood work a year after receiving the revised transplant. Meaning these 7 adult sickle cell disease patients have been cured of the disease by previously deemed incompatible donor stem cells.

Summary of this protocol change is twofold: the new transplant protocol may cure more patients with advanced sickle cell disease; and despite increasing protocol safety and compatibility many sickle cell patients still have to face some barriers, as only 20% of the screened patients were able to undergo a transplants. Denial by medical insurance accounted for 20% of lack of access to the transplant, other factors included patient personal decisions, and high rates of donor specific antigens who received frequent blood transfusions.