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.
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