Medicine and Health Sciences Commons^™

Standardizing Definitions Of Hematopoietic Recovery, Graft Rejection, Graft Failure, Poor Graft Function, And Donor Chimerism In Allogeneic Hematopoietic Cell Transplantation: A Report On Behalf Of The American Society For Transplantation And Cellular Therapy., Mohamed A. Kharfan-Dabaja, Ambuj Kumar, Ernesto Ayala, Mahmoud Aljurf, Taiga Nishihori, Rebecca Marsh, Lauri M. Burroughs, Navneet Majhail, A. Samer Al-Homsi, Zaid S. Al-Kadhimi, Merav Bar, Alice Bertaina, Jaap J. Boelens, Richard Champlin, Sonali Chaudhury, Zachariah Defilipp, Bhagirathbhai Dholaria, Areej El-Jawahri, Suzanne Fanning, Ellen Fraint, Usama Gergis, Sergio Giralt, Betty K. Hamilton, Shahrukh K. Hashmi, Biljana Horn, Yoshihiro Inamoto, David A. Jacobsohn, Tania Jain, Laura Johnston, Abraham S. Kanate, Ankit Kansagra, Adetola Kassim, Leslie S. Kean, Carrie L. Kitko, Jessica Knight-Perry, Joanne Kurtzberg, Hien Liu, Margaret L. Macmillan, Zahra Mahmoudjafari, Marco Mielcarek, Mohamad Mohty, Arnon Nagler, Eneida Nemecek, Timothy S. Olson, Betul Oran, Miguel-Angel Perales, Susan E. Prockop, Michael A. Pulsipher, Iskra Pusic, Marcie L. Riches, Cesar Rodriguez, Rizwan Romee, Gabriela Rondon, Ayman Saad, Nina Shah, Peter J. Shaw, Shalini Shenoy, Jorge Sierra, Julie Talano, Michael R. Verneris, Paul Veys, John E. Wagner, Bipin N. Savani, Mehdi Hamadani, Paul A. Carpenter

Department of Medical Oncology Faculty Papers

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and …

A 2-Step Approach To Myeloablative Haploidentical Stem Cell Transplantation: A Phase 1/2 Trial Performed With Optimized T-Cell Dosing., Dolores Gross, Matthew Carabasi, Joanne Filicko-O'Hara, Margaret Kasner, John L Wagner, Beth Colombe, Patricia Cornett Farley, William O'Hara, Phyllis Flomenberg, Maria Werner-Wasik, Janet Brunner, Bijoyesh Mookerjee, Terry Hyslop, Mark Weiss, Neal Flomenberg

Department of Medical Oncology Faculty Papers

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg …

Ceacam1 Separates Graft-Versus-Host-Disease From Graft-Versus-Tumor Activity After Experimental Allogeneic Bone Marrow Transplantation., Sydney X Lu, Lucy W Kappel, Anne-Marie Charbonneau-Allard, Renée Atallah, Amanda M Holland, Claire Turbide, Vanessa M Hubbard, Jimmy A Rotolo, Marsinay Smith, David Suh, Christopher King, Uttam K Rao, Nury Yim, Johanne L Bautista, Robert R Jenq, Olaf Penack, Il-Kang Na, Chen Liu, George Murphy, Onder Alpdogan, Richard S Blumberg, Fernando Macian, Kathryn V Holmes, Nicole Beauchemin, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.

METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In …

Il-7 Enhances Peripheral T Cell Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation., Onder Alpdogan, Stephanie J Muriglan, Jeffrey M Eng, Lucy M Willis, Andrew S Greenberg, Barry J Kappel, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor alpha chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into …