This project presents a program of experimental therapeutics investigating marrow transplantation. The protocols within this project are closely intergrated with Research Sub Projects. They have been designed and will be analyzed through interactions with the Biostatistics Core II and rely on results of analyses of transplant proposed in Core I. The protocols address major continuing issues in transplantation, namely the genetic and cellular determinants of engraftment and immunologic reconstitution and leukemia resistance in recipients of transplants of HLA-matched or HLA non-identical related or unrelated marrow grafts, and the development of improved transplantation approaches for patients lacking an HLA-matched sibling donor. The protocols, proposed as the specific aims are: 1) Clinical trials of T-cell depleted transplants in related HLA- matched recipients. A. A randomized trial of SBA E T-cell depleted versus unmodified HLA-matched sibling marrow transplants for the treatment of patients with acute leukemia in first or second remision. B. A phase II trial SBA E T-cell depleted marrow grafts combined with infusions of G-CSF stimulated, CD34 CEPRATE stem cell column selected, E-rosette depleted peripheral blood progenitor cells derived from HLA-matched related donors for patients with chemotherapy responsive acute leukemia in late remission or chronic myelogenous leukemia. 2) A phase II trial of T-cell depleted marrow grafts combined with infusions of G-CSF stimulated, CD34 CEPRATE stem cell column selected, E-rosette depleted peripheral blood progenitor cells derived from HLA haplotype matched related donors for patients with leukemia lacking an HLA-matched related or unrelated donor. 3) Amulti-center randomized trial of conventional versus T-cell depleted unrelated marrow transplantation for the treatment of leukemia, non-Hodgkin's lymphoma and myelodysplasia. (The clinical aspects for this trial are supported by a separate contract). 4) A therapeutic trial of donor leukocyte infusions in patients with molecular, cytogenetic or clinical relapse after allogeneic bone marrow transplantation for leukemia. 5) An evaluation of the toxicity and therapeutic effects of Epstein-Barr virus-immune T-lymphocytes derived from a normal HLA-compatible donor in the treatment of EBV-associated lymphoproliferative diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA023766-23
Application #
6336334
Study Section
Project Start
2000-08-01
Project End
2002-02-28
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
23
Fiscal Year
2000
Total Cost
$245,216
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Malard, Florent; Labopin, Myriam; Cho, Christina et al. (2018) Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC. J Hematol Oncol 11:127
Luduec, Jean-BenoƮt Le; Kudva, Anupa; Boudreau, Jeanette E et al. (2018) Novel multiplex PCR-SSP method for centromeric KIR allele discrimination. Sci Rep 8:14853
Shah, Gunjan L; Moskowitz, Craig H (2018) Transplant strategies in relapsed/refractory Hodgkin lymphoma. Blood 131:1689-1697
Avanzi, Mauro P; Yeku, Oladapo; Li, Xinghuo et al. (2018) Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System. Cell Rep 23:2130-2141
Staffas, Anna; Burgos da Silva, Marina; Slingerland, Ann E et al. (2018) Nutritional Support from the Intestinal Microbiota Improves Hematopoietic Reconstitution after Bone Marrow Transplantation in Mice. Cell Host Microbe 23:447-457.e4
Velardi, Enrico; Tsai, Jennifer J; Radtke, Stefan et al. (2018) Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury. Nat Med 24:239-246
Moskowitz, Craig H (2018) Should all patients with HL who relapse after ASCT be considered for allogeneic SCT? A consult, yes; a transplant, not necessarily. Blood Adv 2:821-824
Kim, Seong Jin; Huang, Yao-Ting; Foldi, Julia et al. (2018) Cytomegalovirus resistance in CD34+ -selected hematopoietic cell transplant recipients. Transpl Infect Dis 20:e12881
Maslak, Peter G; Dao, Tao; Bernal, Yvette et al. (2018) Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Adv 2:224-234
DeFilipp, Zachariah; Peled, Jonathan U; Li, Shuli et al. (2018) Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. Blood Adv 2:745-753

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