Bone Marrow Transplantation of Patients in Remission Using Partially Matched Relative Donor

The primary rationale for the development of this research study is to find out if the Thomas Jefferson University (TJU) 2 Step approach to stem cell transplant is an effective treatment for patients with blood cancers who require transplant for long-term survival but are without an available matched-sibling donor. Historically, survival rates for patients undergoing half-matched stem cell transplant have been much lower than those observed after matched sibling stem cell transplant. This may be due to the poor-risk disease features of the patients by the time they are referred for hematopoietic stem cell transplantation (HSCT). Survival post half-matched stem cell transplant has also been affected by the requirement to remove or soothe donor T cells resulting in higher rates of infection and relapse. Newer approaches to haploidentical HSCT, such as the TJU 2 Step approach, utilize cyclophosphamide (CY) to tolerize donor lymphocytes instead of removing them completely from the donor product. This has resulted in less infection without concomitant increase in severe graft-versus-host disease (GVHD) and has increased overall survival as compared to older haploidentical treatment approaches due to decreases in regimen-related morbidity. Because of the historically low overall survival (OS) after haploidentical HSCT, it has become a procedure of last resort with most centers unwilling to consider it unless all other options are exhausted. With the recent development of regimens such as the TJU 2 Step approach which provide safe, alternative platforms for HSCT, it is now feasible, and ethically more acceptable, for patients without matched sibling donors to undergo HSCT prior to being heavily pretreated or developing resistant disease. In this setting, i.e. equivalent regimen safety profiles and more homogenous patient comparison groups, it is possible to more accurately compare antitumor effects between matched sibling donors and haploidentical donors. There is ample evidence in the literature that HLA mismatching causes GVHD. There is not a large body of evidence supporting the notion that HLA mismatching provides superior tumor control translating into greater relapse free survival. As compared to more common types of transplants where donor T cells are given to the recipient, the investigators would surmise that the T cell tolerization associated with the TJU 2 Step approach may decrease the anti-tumor effects of the donor immune system. Conversely, the greater degree of human leukocyte antigen (HLA) mismatch with exploitation of NK effects may mitigate some of the attenuated T cell alloreactivity. Thus, in the context of comparable regimen-related toxicity, our major aim in this research study is to compare graft versus tumor effects as measured by disease-free survival (DFS) between matched sibling HSCT and the TJU 2 Step haploidentical HSCT. If DFS is similar despite T cell tolerization, than the TJU 2 Step haploidentical approach should be considered an effective alternative therapy for those patients in remission without a matched sibling donor. The widespread benefit of this outcome would be the enfranchisement of segments of the population who are without available matched donors resulting in a delay or a failure to receive this potentially life-saving therapy. If DFS survival after treatment on the TJU 2 Step haploidentical approach is superior to what would be expected after matched sibling HSCT, then one could conclude that haploidentical HSCT confers greater tumor control forming the basis for future studies regarding the potential benefits of utilizing haploidentical donors over matched sibling donors when both types of donors are available.