Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies
Status:
Completed
Trial end date:
2020-02-06
Target enrollment:
Participant gender:
Summary
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk
hematologic malignancies. However, most patients do not have an appropriate HLA (immune type)
matched sibling donor available and/or are unable to identify an acceptable unrelated HLA
matched donor through the registries in a timely manner. Another option is haploidentical
transplant using a partially matched family member donor.
Although haploidentical transplant has proven curative in many patients, this procedure has
been hindered by significant complications, primarily regimen-related toxicity including GVHD
and infection due to delayed immune reconstitution. These can, in part, be due to certain
white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize
the body tissues of the patient (the host) are different and attack these cells. Although too
many T cells increase the possibility of GVHD, too few may cause the recipient's immune
system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk
for significant infection.
For these reasons, a primary focus for researchers is to engineer the graft to provide a T
cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to
facilitate immune reconstitution and graft integrity. Building on prior institutional trials,
this study will provide patients with a haploidentical (HAPLO) graft engineered to specific T
cell target values using the CliniMACS system. A reduced intensity, preparative regimen will
be used in an effort to reduce regimen-related toxicity and mortality.
The primary aim of the study is to help improve overall survival with haploidentical stem
cell transplant in this high risk patient population by 1) limiting the complication of graft
versus host disease (GVHD), 2) enhancing post-transplant immune reconstitution, and 3)
reducing non-relapse mortality.