Myeloablative allogeneic bone marrow or stem cell transplantation has been successfully used to cure patients with various types of malignant and nonmalignant diseases. Unfortunately, the risks of this therapy include pulmonary hemorrhage, hepatic failure, severe infections and graft versus host disease. For these reasons, patients who may benefit most from the allogeneic procedure are commonly ineligible for the allogeneic transplant, including those over age 55 years, those with significant prior organ damage, or those with severe infections. Therefore, the investigators and others have developed a less toxic preparative regimen that will successfully allow engraftment of the donor hematopoietic cells while minimizing the risk to the patient of dying of the procedure, thereby making this approach available to a broader array of potential beneficiaries. Importantly, standard post-transplantation care to minimize graft versus host disease still requires aggressive medications with potential severe toxicities. Therefore, they have developed a T-cell depletion protocol using an antibody to CD52 which has been previously shown to be effective for graft versus host disease prophylaxis while maintaining a high engraftment rate and anti-tumor effect of allogeneic therapy. The primary purpose of the translational study in this proposal is to assess the toxicity, engraftment, immune reconstitution and anti-tumor effects of a nonablative conditioning regimen of in vivo Campath-1H, fludarabine, and cyclophosphamide for patients with high risk malignancies. This will be followed by matched-sibling allogeneic peripheral blood stem cell and marrow transplantation (allo, PBSCT) utilizing hematopoietic progenitor cells which are being purged in-vitro with Campath-1H. T-cell depletion with CAMPATH-1H will obviate the need for post-transplant exposure to the toxicities of cyclosporine and methotrexate. These results will lead to future improvements in maximizing the anti-tumor effects of allogeneic therapy, hastening immunologic recovery, and minimizing the toxicity of this procedure.
| Rizzieri, David A; Crout, Christopher; Storms, Robert et al. (2011) Feasibility of low-dose interleukin-2 therapy following T-cell-depleted nonmyeloablative allogeneic hematopoietic stem cell transplantation from HLA-matched or -mismatched family member donors. Cancer Invest 29:56-61 |
| Rizzieri, David A; Storms, Robert; Chen, Dong-Feng et al. (2010) Natural killer cell-enriched donor lymphocyte infusions from A 3-6/6 HLA matched family member following nonmyeloablative allogeneic stem cell transplantation. Biol Blood Marrow Transplant 16:1107-14 |
| Rizzieri, David A; Koh, Liang Piu; Long, Gwynn D et al. (2007) Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution. J Clin Oncol 25:690-7 |
