Reduced dose of posttransplant cyclophosphamide in HLA-haploidentical peripheral blood stem cell transplantation
Posttransplant cyclophosphamide (PTCy:100 mg/kg) has been increasingly used in allogeneic hematopoietic stem cell transplantation, however, few studies compared different doses of PTCy. We conducted two consecutive prospective multicenter phase II studies to evaluate the safety and efficacy of 80 mg...
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creator | Sugita, Junichi Kamimura, Tomohiko Ishikawa, Takayuki Ota, Shuichi Eto, Tetsuya Kuroha, Takashi Miyazaki, Yasuhiko Kumagai, Hiroaki Matsuo, Keitaro Akashi, Koichi Taniguchi, Shuichi Harada, Mine Teshima, Takanori |
description | Posttransplant cyclophosphamide (PTCy:100 mg/kg) has been increasingly used in allogeneic hematopoietic stem cell transplantation, however, few studies compared different doses of PTCy. We conducted two consecutive prospective multicenter phase II studies to evaluate the safety and efficacy of 80 mg/kg of PTCy in 137 patients who underwent HLA-haploidentical peripheral blood stem cell transplantation (haploPBSCT) following reduced-intensity conditioning (RIC). GVHD prophylaxis consisted of PTCy at a dose of 40 mg/kg/day on days 3 and 4, tacrolimus, and mycophenolate mofetil. Neutrophil engraftment was achieved in 97% and 96% in the first and second studies, respectively. The incidences of grades II–IV acute GVHD, III–IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 26%, 5%, 35%, and 18% in the first study, and 23%, 1%, 28%, and 15% in the second study, respectively. Overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) at 2 years were 51%, 42%, and 18% in the first study, and 58%, 48%, and 16% in the second study, respectively. The rates of off-immunosuppressants in patients who survived without relapse at 2 years were 83 and 76%. Our results suggest that 80 mg/kg of PTCy is a valid option in haploPBSCT following RIC. |
doi_str_mv | 10.1038/s41409-020-01065-0 |
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We conducted two consecutive prospective multicenter phase II studies to evaluate the safety and efficacy of 80 mg/kg of PTCy in 137 patients who underwent HLA-haploidentical peripheral blood stem cell transplantation (haploPBSCT) following reduced-intensity conditioning (RIC). GVHD prophylaxis consisted of PTCy at a dose of 40 mg/kg/day on days 3 and 4, tacrolimus, and mycophenolate mofetil. Neutrophil engraftment was achieved in 97% and 96% in the first and second studies, respectively. The incidences of grades II–IV acute GVHD, III–IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 26%, 5%, 35%, and 18% in the first study, and 23%, 1%, 28%, and 15% in the second study, respectively. Overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) at 2 years were 51%, 42%, and 18% in the first study, and 58%, 48%, and 16% in the second study, respectively. The rates of off-immunosuppressants in patients who survived without relapse at 2 years were 83 and 76%. Our results suggest that 80 mg/kg of PTCy is a valid option in haploPBSCT following RIC.</description><identifier>ISSN: 0268-3369</identifier><identifier>EISSN: 1476-5365</identifier><identifier>DOI: 10.1038/s41409-020-01065-0</identifier><identifier>PMID: 32973350</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/100 ; 692/699/1541/1990/283/1897 ; 692/700/565/2319 ; Blood ; Cell Biology ; Cyclophosphamide ; Dosage and administration ; Graft versus host reaction ; Graft vs Host Disease - prevention & control ; Hematology ; Hematopoietic Stem Cell Transplantation ; Hematopoietic stem cells ; Histocompatibility antigen HLA ; Humans ; Immunosuppressive agents ; Internal Medicine ; Leukocytes (neutrophilic) ; Medicine ; Medicine & Public Health ; Mycophenolate mofetil ; Mycophenolic acid ; Peripheral blood ; Peripheral Blood Stem Cell Transplantation ; Prevention ; Prophylaxis ; Prospective Studies ; Public Health ; Risk factors ; Stem cell transplantation ; Stem Cells ; Survival ; Tacrolimus ; Transplantation ; Transplantation Conditioning</subject><ispartof>Bone marrow transplantation (Basingstoke), 2021-03, Vol.56 (3), p.596-604</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-3dd11b2a2fbc5ef67f31a62a1c6f694884266217a3b5336a65a777a2ee2773833</citedby><cites>FETCH-LOGICAL-c539t-3dd11b2a2fbc5ef67f31a62a1c6f694884266217a3b5336a65a777a2ee2773833</cites><orcidid>0000-0003-1761-6314 ; 0000-0003-3852-5075 ; 0000-0002-0941-271X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32973350$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sugita, Junichi</creatorcontrib><creatorcontrib>Kamimura, Tomohiko</creatorcontrib><creatorcontrib>Ishikawa, Takayuki</creatorcontrib><creatorcontrib>Ota, Shuichi</creatorcontrib><creatorcontrib>Eto, Tetsuya</creatorcontrib><creatorcontrib>Kuroha, Takashi</creatorcontrib><creatorcontrib>Miyazaki, Yasuhiko</creatorcontrib><creatorcontrib>Kumagai, Hiroaki</creatorcontrib><creatorcontrib>Matsuo, Keitaro</creatorcontrib><creatorcontrib>Akashi, Koichi</creatorcontrib><creatorcontrib>Taniguchi, Shuichi</creatorcontrib><creatorcontrib>Harada, Mine</creatorcontrib><creatorcontrib>Teshima, Takanori</creatorcontrib><title>Reduced dose of posttransplant cyclophosphamide in HLA-haploidentical peripheral blood stem cell transplantation</title><title>Bone marrow transplantation (Basingstoke)</title><addtitle>Bone Marrow Transplant</addtitle><addtitle>Bone Marrow Transplant</addtitle><description>Posttransplant cyclophosphamide (PTCy:100 mg/kg) has been increasingly used in allogeneic hematopoietic stem cell transplantation, however, few studies compared different doses of PTCy. We conducted two consecutive prospective multicenter phase II studies to evaluate the safety and efficacy of 80 mg/kg of PTCy in 137 patients who underwent HLA-haploidentical peripheral blood stem cell transplantation (haploPBSCT) following reduced-intensity conditioning (RIC). GVHD prophylaxis consisted of PTCy at a dose of 40 mg/kg/day on days 3 and 4, tacrolimus, and mycophenolate mofetil. Neutrophil engraftment was achieved in 97% and 96% in the first and second studies, respectively. The incidences of grades II–IV acute GVHD, III–IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 26%, 5%, 35%, and 18% in the first study, and 23%, 1%, 28%, and 15% in the second study, respectively. Overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) at 2 years were 51%, 42%, and 18% in the first study, and 58%, 48%, and 16% in the second study, respectively. The rates of off-immunosuppressants in patients who survived without relapse at 2 years were 83 and 76%. Our results suggest that 80 mg/kg of PTCy is a valid option in haploPBSCT following RIC.</description><subject>13</subject><subject>13/100</subject><subject>692/699/1541/1990/283/1897</subject><subject>692/700/565/2319</subject><subject>Blood</subject><subject>Cell Biology</subject><subject>Cyclophosphamide</subject><subject>Dosage and administration</subject><subject>Graft versus host reaction</subject><subject>Graft vs Host Disease - prevention & control</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hematopoietic stem cells</subject><subject>Histocompatibility antigen HLA</subject><subject>Humans</subject><subject>Immunosuppressive agents</subject><subject>Internal Medicine</subject><subject>Leukocytes (neutrophilic)</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mycophenolate mofetil</subject><subject>Mycophenolic acid</subject><subject>Peripheral blood</subject><subject>Peripheral Blood Stem Cell Transplantation</subject><subject>Prevention</subject><subject>Prophylaxis</subject><subject>Prospective Studies</subject><subject>Public Health</subject><subject>Risk factors</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>Survival</subject><subject>Tacrolimus</subject><subject>Transplantation</subject><subject>Transplantation 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dose of posttransplant cyclophosphamide in HLA-haploidentical peripheral blood stem cell transplantation</title><author>Sugita, Junichi ; Kamimura, Tomohiko ; Ishikawa, Takayuki ; Ota, Shuichi ; Eto, Tetsuya ; Kuroha, Takashi ; Miyazaki, Yasuhiko ; Kumagai, Hiroaki ; Matsuo, Keitaro ; Akashi, Koichi ; Taniguchi, Shuichi ; Harada, Mine ; Teshima, Takanori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-3dd11b2a2fbc5ef67f31a62a1c6f694884266217a3b5336a65a777a2ee2773833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>13</topic><topic>13/100</topic><topic>692/699/1541/1990/283/1897</topic><topic>692/700/565/2319</topic><topic>Blood</topic><topic>Cell Biology</topic><topic>Cyclophosphamide</topic><topic>Dosage and administration</topic><topic>Graft versus host reaction</topic><topic>Graft vs Host Disease - prevention & 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Transplant</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>56</volume><issue>3</issue><spage>596</spage><epage>604</epage><pages>596-604</pages><issn>0268-3369</issn><eissn>1476-5365</eissn><abstract>Posttransplant cyclophosphamide (PTCy:100 mg/kg) has been increasingly used in allogeneic hematopoietic stem cell transplantation, however, few studies compared different doses of PTCy. We conducted two consecutive prospective multicenter phase II studies to evaluate the safety and efficacy of 80 mg/kg of PTCy in 137 patients who underwent HLA-haploidentical peripheral blood stem cell transplantation (haploPBSCT) following reduced-intensity conditioning (RIC). GVHD prophylaxis consisted of PTCy at a dose of 40 mg/kg/day on days 3 and 4, tacrolimus, and mycophenolate mofetil. Neutrophil engraftment was achieved in 97% and 96% in the first and second studies, respectively. The incidences of grades II–IV acute GVHD, III–IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 26%, 5%, 35%, and 18% in the first study, and 23%, 1%, 28%, and 15% in the second study, respectively. Overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) at 2 years were 51%, 42%, and 18% in the first study, and 58%, 48%, and 16% in the second study, respectively. The rates of off-immunosuppressants in patients who survived without relapse at 2 years were 83 and 76%. Our results suggest that 80 mg/kg of PTCy is a valid option in haploPBSCT following RIC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32973350</pmid><doi>10.1038/s41409-020-01065-0</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-1761-6314</orcidid><orcidid>https://orcid.org/0000-0003-3852-5075</orcidid><orcidid>https://orcid.org/0000-0002-0941-271X</orcidid></addata></record> |
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subjects | 13 13/100 692/699/1541/1990/283/1897 692/700/565/2319 Blood Cell Biology Cyclophosphamide Dosage and administration Graft versus host reaction Graft vs Host Disease - prevention & control Hematology Hematopoietic Stem Cell Transplantation Hematopoietic stem cells Histocompatibility antigen HLA Humans Immunosuppressive agents Internal Medicine Leukocytes (neutrophilic) Medicine Medicine & Public Health Mycophenolate mofetil Mycophenolic acid Peripheral blood Peripheral Blood Stem Cell Transplantation Prevention Prophylaxis Prospective Studies Public Health Risk factors Stem cell transplantation Stem Cells Survival Tacrolimus Transplantation Transplantation Conditioning |
title | Reduced dose of posttransplant cyclophosphamide in HLA-haploidentical peripheral blood stem cell transplantation |
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