Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies

Much of the therapeutic benefit of allogeneic transplant is by a graft versus tumor effect. Further data shows that transplant engraftment is not dependant on myeloablation, instead relying on quantitative competition between donor and host cells. In the clinical setting, engraftment by competition...

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Main Authors: John L. Reagan, Loren D. Fast, Eric S. Winer, Howard Safran, James N. Butera, Peter J. Quesenberry
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Advances in Hematology
Online Access:http://dx.doi.org/10.1155/2012/784213
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author John L. Reagan
Loren D. Fast
Eric S. Winer
Howard Safran
James N. Butera
Peter J. Quesenberry
author_facet John L. Reagan
Loren D. Fast
Eric S. Winer
Howard Safran
James N. Butera
Peter J. Quesenberry
author_sort John L. Reagan
collection DOAJ
description Much of the therapeutic benefit of allogeneic transplant is by a graft versus tumor effect. Further data shows that transplant engraftment is not dependant on myeloablation, instead relying on quantitative competition between donor and host cells. In the clinical setting, engraftment by competition alone is not feasible due to the need for large numbers of infused cells. Instead, low-level host irradiation has proven to be an effective engraftment strategy that is stem cell toxic but not myeloablative. The above observations served as the foundation for clinical trials utilizing allogeneic matched and haploidentical peripheral blood stem cell infusions with minimal conditioning in patients with refractory malignancies. Although engraftment was transient or not apparent, there were compelling responses in a heavily pretreated patient population that appear to result from the breaking of tumor immune tolerance by the host through the actions of IFNγ, invariant NK T cells, CD8 T cells, NK cells, or antigen presenting cells.
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spelling doaj-art-cfe06c96b92e4cc9bec93380d40fc44c2025-08-20T02:20:06ZengWileyAdvances in Hematology1687-91041687-91122012-01-01201210.1155/2012/784213784213Nonengraftment Haploidentical Cellular Therapy for Hematologic MalignanciesJohn L. Reagan0Loren D. Fast1Eric S. Winer2Howard Safran3James N. Butera4Peter J. Quesenberry5Division of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School, Providence, RI 02903, USADivision of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School, Providence, RI 02903, USADivision of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School, Providence, RI 02903, USADivision of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School, Providence, RI 02903, USADivision of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School, Providence, RI 02903, USADivision of Hematology and Oncology, Rhode Island Hospital, The Warren Alpert Medical School, Providence, RI 02903, USAMuch of the therapeutic benefit of allogeneic transplant is by a graft versus tumor effect. Further data shows that transplant engraftment is not dependant on myeloablation, instead relying on quantitative competition between donor and host cells. In the clinical setting, engraftment by competition alone is not feasible due to the need for large numbers of infused cells. Instead, low-level host irradiation has proven to be an effective engraftment strategy that is stem cell toxic but not myeloablative. The above observations served as the foundation for clinical trials utilizing allogeneic matched and haploidentical peripheral blood stem cell infusions with minimal conditioning in patients with refractory malignancies. Although engraftment was transient or not apparent, there were compelling responses in a heavily pretreated patient population that appear to result from the breaking of tumor immune tolerance by the host through the actions of IFNγ, invariant NK T cells, CD8 T cells, NK cells, or antigen presenting cells.http://dx.doi.org/10.1155/2012/784213
spellingShingle John L. Reagan
Loren D. Fast
Eric S. Winer
Howard Safran
James N. Butera
Peter J. Quesenberry
Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies
Advances in Hematology
title Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies
title_full Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies
title_fullStr Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies
title_full_unstemmed Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies
title_short Nonengraftment Haploidentical Cellular Therapy for Hematologic Malignancies
title_sort nonengraftment haploidentical cellular therapy for hematologic malignancies
url http://dx.doi.org/10.1155/2012/784213
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