T‐cell–depleted haploidentical stem cell transplantation results improve with time in adults with acute leukemia: A study from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT)

BACKGROUND T‐cell–depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high‐risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full‐matched donor. METHODS To determine the effect of transplantation period, the authors divided 308 adults wit...

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Veröffentlicht in:Cancer 2018-05, Vol.124 (10), p.2142-2150
Hauptverfasser: Sestili, Simona, Labopin, Myriam, Ruggeri, Annalisa, Velardi, Andrea, Ciceri, Fabio, Maertens, Johan, Kanz, Lothar, Aversa, Franco, Lewalle, Philippe, Bunjes, Donald, Mohty, Mohamad, Nagler, Arnon
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container_issue 10
container_start_page 2142
container_title Cancer
container_volume 124
creator Sestili, Simona
Labopin, Myriam
Ruggeri, Annalisa
Velardi, Andrea
Ciceri, Fabio
Maertens, Johan
Kanz, Lothar
Aversa, Franco
Lewalle, Philippe
Bunjes, Donald
Mohty, Mohamad
Nagler, Arnon
description BACKGROUND T‐cell–depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high‐risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full‐matched donor. METHODS To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T‐cell–depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005‐2011 [n = 191] and 2012‐2015 [n = 117]). RESULTS The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft‐versus‐host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2‐year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced‐intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2‐year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival. Similarly, leukemia‐free survival and GvHD‐free/relapse‐free survival (GRFS) improved over time: the leukemia‐free survival rate was 31% (25% vs 43% in the groups who underwent transplantation before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs 34%, respectively; P = .09). In addition, leukemia‐free survival and GRFS improved among patients who received a RIC regimen. CONCLUSIONS The outcome of patients with acute leukemia who underwent T‐cell–dep
doi_str_mv 10.1002/cncr.31310
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METHODS To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T‐cell–depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005‐2011 [n = 191] and 2012‐2015 [n = 117]). RESULTS The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft‐versus‐host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2‐year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced‐intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2‐year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival. Similarly, leukemia‐free survival and GvHD‐free/relapse‐free survival (GRFS) improved over time: the leukemia‐free survival rate was 31% (25% vs 43% in the groups who underwent transplantation before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs 34%, respectively; P = .09). In addition, leukemia‐free survival and GRFS improved among patients who received a RIC regimen. CONCLUSIONS The outcome of patients with acute leukemia who underwent T‐cell–depleted haplo has improved over time. Cancer 2018;124:2142‐50. © 2018 American Cancer Society. Outcomes of T‐cell–depleted, haploidentical transplantation for acute leukemia in Europe have improved over time. In this registry‐based study, 208 patients are divided into 2 groups according to the era of transplantation (2005‐2011 [n = 191] and 2012‐2015 [n = 117]), and the results demonstrate 36% 2‐year overall survival, 31% overall leukemia‐free survival, 24% graft‐versus‐host disease‐free/relapse‐free survival, and a marked improvement for those who underwent T‐cell–depleted, haploidentical transplantation after 2012 and received a reduced‐intensity conditioning regimen.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.31310</identifier><identifier>PMID: 29469924</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>acute leukemia ; Acute myeloid leukemia ; Adults ; Cancer ; Depletion ; Graft-versus-host reaction ; haploidentical transplantation ; Histocompatibility antigen HLA ; Incidence ; Leukemia ; Leukocytes ; Lymphocytes T ; Multivariate analysis ; Myeloid leukemia ; Oncology ; outcomes ; Patients ; Remission ; Stem cell transplantation ; Stem cells ; Survival ; time ; Transplantation ; T‐cell depletion</subject><ispartof>Cancer, 2018-05, Vol.124 (10), p.2142-2150</ispartof><rights>2018 American Cancer Society</rights><rights>2018 American Cancer Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3930-e583fd4960dd92f18c34b2312f1654e7f200299a513475762ece9e41beb49d843</citedby><cites>FETCH-LOGICAL-c3930-e583fd4960dd92f18c34b2312f1654e7f200299a513475762ece9e41beb49d843</cites><orcidid>0000-0003-4083-6972 ; 0000-0002-7261-2765</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcncr.31310$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncr.31310$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29469924$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sestili, Simona</creatorcontrib><creatorcontrib>Labopin, Myriam</creatorcontrib><creatorcontrib>Ruggeri, Annalisa</creatorcontrib><creatorcontrib>Velardi, Andrea</creatorcontrib><creatorcontrib>Ciceri, Fabio</creatorcontrib><creatorcontrib>Maertens, Johan</creatorcontrib><creatorcontrib>Kanz, Lothar</creatorcontrib><creatorcontrib>Aversa, Franco</creatorcontrib><creatorcontrib>Lewalle, Philippe</creatorcontrib><creatorcontrib>Bunjes, Donald</creatorcontrib><creatorcontrib>Mohty, Mohamad</creatorcontrib><creatorcontrib>Nagler, Arnon</creatorcontrib><title>T‐cell–depleted haploidentical stem cell transplantation results improve with time in adults with acute leukemia: A study from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT)</title><title>Cancer</title><addtitle>Cancer</addtitle><description>BACKGROUND T‐cell–depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high‐risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full‐matched donor. METHODS To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T‐cell–depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005‐2011 [n = 191] and 2012‐2015 [n = 117]). RESULTS The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft‐versus‐host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2‐year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced‐intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2‐year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival. Similarly, leukemia‐free survival and GvHD‐free/relapse‐free survival (GRFS) improved over time: the leukemia‐free survival rate was 31% (25% vs 43% in the groups who underwent transplantation before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs 34%, respectively; P = .09). In addition, leukemia‐free survival and GRFS improved among patients who received a RIC regimen. CONCLUSIONS The outcome of patients with acute leukemia who underwent T‐cell–depleted haplo has improved over time. Cancer 2018;124:2142‐50. © 2018 American Cancer Society. Outcomes of T‐cell–depleted, haploidentical transplantation for acute leukemia in Europe have improved over time. In this registry‐based study, 208 patients are divided into 2 groups according to the era of transplantation (2005‐2011 [n = 191] and 2012‐2015 [n = 117]), and the results demonstrate 36% 2‐year overall survival, 31% overall leukemia‐free survival, 24% graft‐versus‐host disease‐free/relapse‐free survival, and a marked improvement for those who underwent T‐cell–depleted, haploidentical transplantation after 2012 and received a reduced‐intensity conditioning regimen.</description><subject>acute leukemia</subject><subject>Acute myeloid leukemia</subject><subject>Adults</subject><subject>Cancer</subject><subject>Depletion</subject><subject>Graft-versus-host reaction</subject><subject>haploidentical transplantation</subject><subject>Histocompatibility antigen HLA</subject><subject>Incidence</subject><subject>Leukemia</subject><subject>Leukocytes</subject><subject>Lymphocytes T</subject><subject>Multivariate analysis</subject><subject>Myeloid leukemia</subject><subject>Oncology</subject><subject>outcomes</subject><subject>Patients</subject><subject>Remission</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Survival</subject><subject>time</subject><subject>Transplantation</subject><subject>T‐cell depletion</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp90c1uEzEQB_AVAtFQuPAAaCQuBSnFXnt3Y25pFD6kFBAEwW3lrGeJW6-92F6i3PoISLxhDzwHTlI49MDJXz__NZrJsseUnFJC8heNbfwpo4ySO9mIElGNCeX53WxECJmMC86-HmUPQrhIxyov2P3sKBe8FCLno-z38vrqZ4PGXF_9UtgbjKhgLXvjtEIbdSMNhIgd7AxEL23ojbRRRu0seAyDiQF013v3A2Gj4xqi7hC0Ban2b_s72QwRweBwiZ2WL2GaQge1hda7DuIaYboHixsAX5y_1PYbfJA-bsG1ezMfvOtRWvjkGo2H-zPjnAJpFZxL790GlrdKPJmfnS-fPczutdIEfHSzHmefX82XszfjxfvXb2fTxbhhgpExFhPWKi5KopTIWzppGF_ljKZtWXCs2jz1WwhZUMaroipzbFAgpytccaEmnB1nJ4fc1I_vA4ZYdzrsWictuiHU6X_Fc8G4SPTpLXrhBm9TdUkxzoqy5GVSzw-q8S4Ej23de91Jv60pqXfTr3fTr_fTT_jJTeSw6lD9o3_HnQA9gI02uP1PVD17N_t4CP0Do1a_hA</recordid><startdate>20180515</startdate><enddate>20180515</enddate><creator>Sestili, Simona</creator><creator>Labopin, Myriam</creator><creator>Ruggeri, Annalisa</creator><creator>Velardi, Andrea</creator><creator>Ciceri, Fabio</creator><creator>Maertens, Johan</creator><creator>Kanz, Lothar</creator><creator>Aversa, Franco</creator><creator>Lewalle, Philippe</creator><creator>Bunjes, Donald</creator><creator>Mohty, Mohamad</creator><creator>Nagler, Arnon</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4083-6972</orcidid><orcidid>https://orcid.org/0000-0002-7261-2765</orcidid></search><sort><creationdate>20180515</creationdate><title>T‐cell–depleted haploidentical stem cell transplantation results improve with time in adults with acute leukemia: A study from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT)</title><author>Sestili, Simona ; Labopin, Myriam ; Ruggeri, Annalisa ; Velardi, Andrea ; Ciceri, Fabio ; Maertens, Johan ; Kanz, Lothar ; Aversa, Franco ; Lewalle, Philippe ; Bunjes, Donald ; Mohty, Mohamad ; Nagler, Arnon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3930-e583fd4960dd92f18c34b2312f1654e7f200299a513475762ece9e41beb49d843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>acute leukemia</topic><topic>Acute myeloid leukemia</topic><topic>Adults</topic><topic>Cancer</topic><topic>Depletion</topic><topic>Graft-versus-host reaction</topic><topic>haploidentical transplantation</topic><topic>Histocompatibility antigen HLA</topic><topic>Incidence</topic><topic>Leukemia</topic><topic>Leukocytes</topic><topic>Lymphocytes T</topic><topic>Multivariate analysis</topic><topic>Myeloid leukemia</topic><topic>Oncology</topic><topic>outcomes</topic><topic>Patients</topic><topic>Remission</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Survival</topic><topic>time</topic><topic>Transplantation</topic><topic>T‐cell depletion</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sestili, Simona</creatorcontrib><creatorcontrib>Labopin, Myriam</creatorcontrib><creatorcontrib>Ruggeri, Annalisa</creatorcontrib><creatorcontrib>Velardi, Andrea</creatorcontrib><creatorcontrib>Ciceri, Fabio</creatorcontrib><creatorcontrib>Maertens, Johan</creatorcontrib><creatorcontrib>Kanz, Lothar</creatorcontrib><creatorcontrib>Aversa, Franco</creatorcontrib><creatorcontrib>Lewalle, Philippe</creatorcontrib><creatorcontrib>Bunjes, Donald</creatorcontrib><creatorcontrib>Mohty, Mohamad</creatorcontrib><creatorcontrib>Nagler, Arnon</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; 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METHODS To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T‐cell–depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005‐2011 [n = 191] and 2012‐2015 [n = 117]). RESULTS The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft‐versus‐host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2‐year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced‐intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2‐year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival. Similarly, leukemia‐free survival and GvHD‐free/relapse‐free survival (GRFS) improved over time: the leukemia‐free survival rate was 31% (25% vs 43% in the groups who underwent transplantation before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs 34%, respectively; P = .09). In addition, leukemia‐free survival and GRFS improved among patients who received a RIC regimen. CONCLUSIONS The outcome of patients with acute leukemia who underwent T‐cell–depleted haplo has improved over time. Cancer 2018;124:2142‐50. © 2018 American Cancer Society. Outcomes of T‐cell–depleted, haploidentical transplantation for acute leukemia in Europe have improved over time. In this registry‐based study, 208 patients are divided into 2 groups according to the era of transplantation (2005‐2011 [n = 191] and 2012‐2015 [n = 117]), and the results demonstrate 36% 2‐year overall survival, 31% overall leukemia‐free survival, 24% graft‐versus‐host disease‐free/relapse‐free survival, and a marked improvement for those who underwent T‐cell–depleted, haploidentical transplantation after 2012 and received a reduced‐intensity conditioning regimen.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29469924</pmid><doi>10.1002/cncr.31310</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-4083-6972</orcidid><orcidid>https://orcid.org/0000-0002-7261-2765</orcidid><oa>free_for_read</oa></addata></record>
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source Wiley-Blackwell Journals; Wiley Free Archive; Alma/SFX Local Collection; EZB*
subjects acute leukemia
Acute myeloid leukemia
Adults
Cancer
Depletion
Graft-versus-host reaction
haploidentical transplantation
Histocompatibility antigen HLA
Incidence
Leukemia
Leukocytes
Lymphocytes T
Multivariate analysis
Myeloid leukemia
Oncology
outcomes
Patients
Remission
Stem cell transplantation
Stem cells
Survival
time
Transplantation
T‐cell depletion
title T‐cell–depleted haploidentical stem cell transplantation results improve with time in adults with acute leukemia: A study from the Acute Leukemia Working Party of the European Society of Blood and Marrow Transplantation (EBMT)
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