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Allogeneic transplantation using CD34+ selected peripheral blood progenitor cells combined with non-mobilized donor Tᅡ cells for refractory severe aplastic anaemia

Summary Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bo...

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Published in:British journal of haematology 2017-03, Vol.176 (6), p.950
Main Authors: Purev, Enkhtsetseg, Tian, Xin, Aue, Georg, Pantin, Jeremy, Vo, Phuong, Shalabi, Reem, Reger, Robert N, Cook, Lisa, Ramos, Catalina, Cho, Elena, Worthy, Tat'yana, Khuu, Hanh, Stroncek, David, Young, Neal S, Childs, Richard W
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container_issue 6
container_start_page 950
container_title British journal of haematology
container_volume 176
creator Purev, Enkhtsetseg
Tian, Xin
Aue, Georg
Pantin, Jeremy
Vo, Phuong
Shalabi, Reem
Reger, Robert N
Cook, Lisa
Ramos, Catalina
Cho, Elena
Worthy, Tat'yana
Khuu, Hanh
Stroncek, David
Young, Neal S
Childs, Richard W
description Summary Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34+ selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells. Fifteen patients with refractory SAA received cyclophosphamide, anti-thymocyte globulin and fludarabine conditioning, and were transplanted with a median 8 × 106 CD34+ cells/kg and 2 × 107 non-mobilized CD3+ T-cells/kg from human leucocyte antigen-matched sibling donors. All achieved sustained engraftment with only two developing acute and two developing chronic GVHD. With a 3·5-year median follow-up, 86% of patients survived and were transfusion-independent. When compared to a retrospective cohort of 56 bone-marrow failure patients that received the identical transplant preparative regimen and GVHD prophylaxis with the exception that the allograft contained unmanipulated PBSCs, partial T-cell depleted transplant recipients had delayed donor T-cell chimerism and relative reduction of 75% in the incidence of acute grade II-IV GVHD (13% vs. 52%; P = 0·010) and of 82% in chronic GVHD (13% vs. 72%; P = 0·0004). In multivariate analysis, partial T-cell depleted transplants remained significantly associated with a reduced risk of GVHD. In conclusion, for patients with refractory SAA, this novel transplant strategy achieves excellent engraftment and survival when compared to unmanipulated PBSC transplants and dramatically reduces the incidence of both acute and chronic GVHD.
doi_str_mv 10.1111/bjh.14448
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To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34+ selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells. Fifteen patients with refractory SAA received cyclophosphamide, anti-thymocyte globulin and fludarabine conditioning, and were transplanted with a median 8 × 106 CD34+ cells/kg and 2 × 107 non-mobilized CD3+ T-cells/kg from human leucocyte antigen-matched sibling donors. All achieved sustained engraftment with only two developing acute and two developing chronic GVHD. With a 3·5-year median follow-up, 86% of patients survived and were transfusion-independent. When compared to a retrospective cohort of 56 bone-marrow failure patients that received the identical transplant preparative regimen and GVHD prophylaxis with the exception that the allograft contained unmanipulated PBSCs, partial T-cell depleted transplant recipients had delayed donor T-cell chimerism and relative reduction of 75% in the incidence of acute grade II-IV GVHD (13% vs. 52%; P = 0·010) and of 82% in chronic GVHD (13% vs. 72%; P = 0·0004). In multivariate analysis, partial T-cell depleted transplants remained significantly associated with a reduced risk of GVHD. 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To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34+ selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells. Fifteen patients with refractory SAA received cyclophosphamide, anti-thymocyte globulin and fludarabine conditioning, and were transplanted with a median 8 × 106 CD34+ cells/kg and 2 × 107 non-mobilized CD3+ T-cells/kg from human leucocyte antigen-matched sibling donors. All achieved sustained engraftment with only two developing acute and two developing chronic GVHD. With a 3·5-year median follow-up, 86% of patients survived and were transfusion-independent. When compared to a retrospective cohort of 56 bone-marrow failure patients that received the identical transplant preparative regimen and GVHD prophylaxis with the exception that the allograft contained unmanipulated PBSCs, partial T-cell depleted transplant recipients had delayed donor T-cell chimerism and relative reduction of 75% in the incidence of acute grade II-IV GVHD (13% vs. 52%; P = 0·010) and of 82% in chronic GVHD (13% vs. 72%; P = 0·0004). In multivariate analysis, partial T-cell depleted transplants remained significantly associated with a reduced risk of GVHD. In conclusion, for patients with refractory SAA, this novel transplant strategy achieves excellent engraftment and survival when compared to unmanipulated PBSC transplants and dramatically reduces the incidence of both acute and chronic GVHD.</description><subject>Allografts</subject><subject>Anemia</subject><subject>Bone marrow</subject><subject>Bone marrow transplantation</subject><subject>CD3 antigen</subject><subject>CD34 antigen</subject><subject>Chimerism</subject><subject>Colony-stimulating factor</subject><subject>Conditioning</subject><subject>Cyclophosphamide</subject><subject>Depletion</subject><subject>Donors</subject><subject>Fludarabine</subject><subject>Globulins</subject><subject>Graft rejection</subject><subject>Graft-versus-host reaction</subject><subject>Grafting</subject><subject>Granulocyte colony-stimulating factor</subject><subject>Hematology</subject><subject>Hematopoietic stem cells</subject><subject>Hemopoiesis</subject><subject>Immunosuppressive agents</subject><subject>Incidence</subject><subject>Leukocytes (granulocytic)</subject><subject>Lymphocytes T</subject><subject>Multivariate analysis</subject><subject>Peripheral blood</subject><subject>Prophylaxis</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Transfusion</subject><subject>Transplantation</subject><subject>Transplants &amp; 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implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Purev, Enkhtsetseg</creatorcontrib><creatorcontrib>Tian, Xin</creatorcontrib><creatorcontrib>Aue, Georg</creatorcontrib><creatorcontrib>Pantin, Jeremy</creatorcontrib><creatorcontrib>Vo, Phuong</creatorcontrib><creatorcontrib>Shalabi, Reem</creatorcontrib><creatorcontrib>Reger, Robert N</creatorcontrib><creatorcontrib>Cook, Lisa</creatorcontrib><creatorcontrib>Ramos, Catalina</creatorcontrib><creatorcontrib>Cho, Elena</creatorcontrib><creatorcontrib>Worthy, Tat'yana</creatorcontrib><creatorcontrib>Khuu, Hanh</creatorcontrib><creatorcontrib>Stroncek, David</creatorcontrib><creatorcontrib>Young, Neal S</creatorcontrib><creatorcontrib>Childs, Richard W</creatorcontrib><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Purev, Enkhtsetseg</au><au>Tian, Xin</au><au>Aue, Georg</au><au>Pantin, Jeremy</au><au>Vo, Phuong</au><au>Shalabi, Reem</au><au>Reger, Robert N</au><au>Cook, Lisa</au><au>Ramos, Catalina</au><au>Cho, Elena</au><au>Worthy, Tat'yana</au><au>Khuu, Hanh</au><au>Stroncek, David</au><au>Young, Neal S</au><au>Childs, Richard W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Allogeneic transplantation using CD34+ selected peripheral blood progenitor cells combined with non-mobilized donor Tᅡ cells for refractory severe aplastic anaemia</atitle><jtitle>British journal of haematology</jtitle><date>2017-03-01</date><risdate>2017</risdate><volume>176</volume><issue>6</issue><spage>950</spage><pages>950-</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><abstract>Summary Allogeneic haematopoietic stem cell transplantation is curative for severe aplastic anaemia (SAA) unresponsive to immunosuppressive therapy. To reduce chronic graft-versus-host disease (GVHD), which occurs more frequently after peripheral blood stem cell (PBSC) transplantation compared to bone-marrow transplantation (BMT), and to prevent graft rejection, we developed a novel partial T-cell depleted transplant that infuses high numbers of granulocyte colony-stimulating factor-mobilized CD34+ selected PBSCs combined with a BMT-equivalent dose of non-mobilized donor T-cells. Fifteen patients with refractory SAA received cyclophosphamide, anti-thymocyte globulin and fludarabine conditioning, and were transplanted with a median 8 × 106 CD34+ cells/kg and 2 × 107 non-mobilized CD3+ T-cells/kg from human leucocyte antigen-matched sibling donors. All achieved sustained engraftment with only two developing acute and two developing chronic GVHD. With a 3·5-year median follow-up, 86% of patients survived and were transfusion-independent. When compared to a retrospective cohort of 56 bone-marrow failure patients that received the identical transplant preparative regimen and GVHD prophylaxis with the exception that the allograft contained unmanipulated PBSCs, partial T-cell depleted transplant recipients had delayed donor T-cell chimerism and relative reduction of 75% in the incidence of acute grade II-IV GVHD (13% vs. 52%; P = 0·010) and of 82% in chronic GVHD (13% vs. 72%; P = 0·0004). In multivariate analysis, partial T-cell depleted transplants remained significantly associated with a reduced risk of GVHD. In conclusion, for patients with refractory SAA, this novel transplant strategy achieves excellent engraftment and survival when compared to unmanipulated PBSC transplants and dramatically reduces the incidence of both acute and chronic GVHD.</abstract><cop>Oxford</cop><pub>Blackwell Publishing Ltd</pub><doi>10.1111/bjh.14448</doi></addata></record>
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ispartof British journal of haematology, 2017-03, Vol.176 (6), p.950
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1365-2141
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subjects Allografts
Anemia
Bone marrow
Bone marrow transplantation
CD3 antigen
CD34 antigen
Chimerism
Colony-stimulating factor
Conditioning
Cyclophosphamide
Depletion
Donors
Fludarabine
Globulins
Graft rejection
Graft-versus-host reaction
Grafting
Granulocyte colony-stimulating factor
Hematology
Hematopoietic stem cells
Hemopoiesis
Immunosuppressive agents
Incidence
Leukocytes (granulocytic)
Lymphocytes T
Multivariate analysis
Peripheral blood
Prophylaxis
Stem cell transplantation
Stem cells
Transfusion
Transplantation
Transplants & implants
title Allogeneic transplantation using CD34+ selected peripheral blood progenitor cells combined with non-mobilized donor Tᅡ cells for refractory severe aplastic anaemia
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