While HCT offers potentially curative therapy to patients with a variety of benign and malignant diseases, both acute and chronic graft versus host disease (GVHD) continue to plague the field and often limit the longevity and quality of life of our patients. While either bone marrow (BM) or mobilized peripheral blood (MPB) are suitable sources of donor hematopoietic cells, this network established in BMT CTN 0201 that granulocyte colony stimulating factor (G-CSF) MPB is associated with a higher risk of chronic GVHD (cGVHD) and worse quality of life following unrelated donor HCT compared to BM. Similar results have been demonstrated in recipients of MPB from matched siblings. The Ohio State Blood and Marrow Transplant Research Consortium (OSUBMT- RC) is comprised of five highly experienced transplant centers with a well-established track record of productivity conducting clinical trials. Our consortium proposes a novel approach to limiting GVHD following HCT by establishing a new standard for the procurement of donor hematopoietic cells for transplantation. The OSUBMT- RC PI has pioneered a novel method to procure donor cells for HCT using the CXCR4 antagonist plerixafor without G-CSF. Plerixafor mobilizes CD34+ cells and other immune cells for transplantation far more rapidly than G-CSF (1 vs 5 days), with less toxicity to the donor. Grafts procured following plerixafor alone (P-MPB) promote full engraftment and based on a recent multi-center phase II study led by the PI, appear to reconstitute immunity faster than G-MPB and may cause less chronic GVHD (cGVHD). These advantages appear to be particularly striking in older patients receiving reduced intensity allografts. Based on these data, we hypothesize that P-MPB will become a suitable and possibly preferable alternative method to procure MPB for HCT due to the combination of better convenience and less toxicity for donors and less GVHD combined with better immune reconstitution in recipients. We propose to test these hypotheses with the following specific aims:
Aim 1 : We will conduct a randomized Phase II study of P-MPB versus G-MPB in recipients of matched sibling donor allografts with cGVHD-free, relapse free survival as the primary endpoint.
Aim 2 : We will test the hypothesis that immune reconstitution is improved with P-MPB versus G-MPB through correlative phenotypical, functional, and gene sequence based studies of T, B, NK, and dendritic cells procured from allograft recipients following HCT The proposed study addresses several key priorities of the BMT CTN established at the 2014 State of the Science Symposium and if promising will pave the way for a future definitive Phase III trial that could radically improve our process for collecting allografts from donors.
Many patients who receive and blood or marrow transplant for hematological or immune system disorders experience devastating complications such as graft versus host disease (GVHD) and infections due to poor immune system recovery. This proposal seeks to improve this situation by developing a safer and more effective method to collect stem cells from donors. This method works more rapidly than traditional methods and can improve immune system recovery and lessen GVHD in the transplant recipients, resulting in better outcomes.
