Haplo-identical Stem Cell Transplantation (SCT) for High-Risk Hematologic Malignancies With Post-Transplant In-Vivo T-cell Depletion

For patients whose disease cannot be brought into remission the prognoses are worse primarily due to high rates of post-HSCT relapse. For patients who have poor donor options (i.e., lack an adequately matched allogeneic marrow donor), the prognoses are worse for a successful outcome due to higher rates of treatment related mortality (TRM). Their options are to seek investigational treatments without HSCT or alternative investigational HSCT protocols for which they are eligible. Patients who have relapsed after an allogeneic HSCT are at high risk for either relapse or TRM after a subsequent HSCT, even if an additional state of complete remission can be achieved prior to the subsequent HSCT.

This current treatment protocol is designed to assess alternative HSCT treatments for patients with refractory/very high risk disease features and/or inadequate single sources of human leukocyte antigen (HLA)- matched -donor stem cells. The goal is to cure their hematological malignancy with the combination of chemotherapy and potentially destruction of cancerous cells by the new, donor immune cells.

For patients whose only potential for cure is allogeneic HSCT but who are lacking a well matched relative or unrelated donor source, haplo-identical donors (i.e., "half identical" donors) are a remaining option. However, without some form of immune manipulation of the donor marrow (e.g. pre-infusion in vitro or in the test tube/laboratory T-depletion, or depletion of donor T-cells), outcomes after haplo-identical HSCT have very poor results with unacceptable TRM, non-engraftment or severe graft-vs-host disease (GVHD)2 leading to fatal complications. GVHD is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted donor cells attack the healthy tissues in the transplant recipient's body.

Thus, to better treat resistant leukemia, there is a need for either improved cytoreduction (pre-transplant reduction in the number of the cancer/leukemia cells) regimens for refractory disease, and/or for improved methods of eliminating cancer cells after the transplant has occurred.

Using well matched donors, investigators have studied the use of HSCT using mild chemotherapy but exploiting the donor cell immune reaction post-stem cell infusion to "allow" the reaction against leukemia and lymphoma cancer cells. This has generally proven ineffective for patients with disease not in remission at the time of transplant.