High lactate dehydrogenase at time of admission for allogeneic hematopoietic transplantation associates to poor survival in acute myeloid leukemia and non-Hodgkin lymphoma
Risk stratification is important for balancing potential risks and benefits of allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. We retrospectively studied 1119 patients undergoing allogenic-HSCT in a single center for five hematological indications assessing...
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| Veröffentlicht in: | Bone marrow transplantation (Basingstoke) 2021-11, Vol.56 (11), p.2690-2696 |
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| creator | Geva, Mika Pryce, Angharad Shouval, Roni Fein, Joshua A. Danylesko, Ivetta Shem-Tov, Noga Yerushalmi, Ronit Shimoni, Avichai Szydlo, Richard Pavlu, Jiri Nagler, Arnon |
| description | Risk stratification is important for balancing potential risks and benefits of allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. We retrospectively studied 1119 patients undergoing allogenic-HSCT in a single center for five hematological indications assessing the prognostic role of LDH at admission for survival (OS), progression-free survival (PFS), relapse incidence (RI), and nonrelapse mortality (NRM). In non-Hodgkin lymphoma (NHL) and acute myeloid leukemia (AML), higher than median LDH had an adverse effect on survival. The prognostic significance was strongest in AML, with higher LDH levels having lower 1-and 3-year survival 69.2% vs. 50.8%,
P
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| doi_str_mv | 10.1038/s41409-021-01377-9 |
| format | Article |
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P
< 0.001 and 51.9% vs. 39.2%,
P
< 0.001, respectively, reduced 1-and 3-year PFS 62.4% vs. 42.1%,
P
< 0.001 48% vs. 35.2%,
P
< 0.001, respectively, higher cumulative incidence of 1-and 3-year NRM 11% vs. 17.3%,
p
= 0.01 and 15.7% vs. 19.6%,
P
= 0.04, and higher 1-and 3-year relapse incidence (RI) 26.7% vs. 40.7%,
p
< .0001 36.2% vs. 40.7%, respectively,
P
< 0.0001). In multivariate analysis LDH maintained significant prognostic capacity in OS, PFS and RI. These findings in AML, validated in an independent cohort, suggest that LDH is a readily available tool that could be integrated into transplant risk assessments to aid decision-making and identify high-risk patients who may benefit from post-transplant pharmacological or cellular strategies.]]></description><identifier>ISSN: 0268-3369</identifier><identifier>EISSN: 1476-5365</identifier><identifier>DOI: 10.1038/s41409-021-01377-9</identifier><identifier>PMID: 34188181</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/499 ; 692/699/1541/1990 ; Acute myeloid leukemia ; Care and treatment ; Cell Biology ; Decision making ; Health aspects ; Hematology ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic stem cells ; Homografts ; Humans ; Internal Medicine ; L-Lactate Dehydrogenase ; Lactate dehydrogenase ; Lactic acid ; Leukemia ; Leukemia, Myeloid, Acute ; Lymphoma ; Lymphoma, Non-Hodgkin - therapy ; Medicine ; Medicine & Public Health ; Multivariate analysis ; Myeloid leukemia ; Non-Hodgkin's lymphoma ; Non-Hodgkin's lymphomas ; Patient outcomes ; Public Health ; Retrospective Studies ; Risk assessment ; Risk groups ; Stem cell transplantation ; Stem Cells ; Survival ; Testing ; Transplantation ; Transplantation Conditioning ; Transplants & implants</subject><ispartof>Bone marrow transplantation (Basingstoke), 2021-11, Vol.56 (11), p.2690-2696</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Nature Limited.</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-c904e874f28d41923f9a0239783d59bb4fb22186ba913919fae1f4e8b77b77e23</citedby><cites>FETCH-LOGICAL-c434t-c904e874f28d41923f9a0239783d59bb4fb22186ba913919fae1f4e8b77b77e23</cites><orcidid>0000-0001-8420-8340 ; 0000-0003-3473-3272 ; 0000-0001-5441-1516 ; 0000-0002-0763-1265 ; 0000-0003-1102-8298 ; 0000-0001-9827-8032</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41409-021-01377-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41409-021-01377-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34188181$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Geva, Mika</creatorcontrib><creatorcontrib>Pryce, Angharad</creatorcontrib><creatorcontrib>Shouval, Roni</creatorcontrib><creatorcontrib>Fein, Joshua A.</creatorcontrib><creatorcontrib>Danylesko, Ivetta</creatorcontrib><creatorcontrib>Shem-Tov, Noga</creatorcontrib><creatorcontrib>Yerushalmi, Ronit</creatorcontrib><creatorcontrib>Shimoni, Avichai</creatorcontrib><creatorcontrib>Szydlo, Richard</creatorcontrib><creatorcontrib>Pavlu, Jiri</creatorcontrib><creatorcontrib>Nagler, Arnon</creatorcontrib><title>High lactate dehydrogenase at time of admission for allogeneic hematopoietic transplantation associates to poor survival in acute myeloid leukemia and non-Hodgkin lymphoma</title><title>Bone marrow transplantation (Basingstoke)</title><addtitle>Bone Marrow Transplant</addtitle><addtitle>Bone Marrow Transplant</addtitle><description><![CDATA[Risk stratification is important for balancing potential risks and benefits of allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. We retrospectively studied 1119 patients undergoing allogenic-HSCT in a single center for five hematological indications assessing the prognostic role of LDH at admission for survival (OS), progression-free survival (PFS), relapse incidence (RI), and nonrelapse mortality (NRM). In non-Hodgkin lymphoma (NHL) and acute myeloid leukemia (AML), higher than median LDH had an adverse effect on survival. The prognostic significance was strongest in AML, with higher LDH levels having lower 1-and 3-year survival 69.2% vs. 50.8%,
P
< 0.001 and 51.9% vs. 39.2%,
P
< 0.001, respectively, reduced 1-and 3-year PFS 62.4% vs. 42.1%,
P
< 0.001 48% vs. 35.2%,
P
< 0.001, respectively, higher cumulative incidence of 1-and 3-year NRM 11% vs. 17.3%,
p
= 0.01 and 15.7% vs. 19.6%,
P
= 0.04, and higher 1-and 3-year relapse incidence (RI) 26.7% vs. 40.7%,
p
< .0001 36.2% vs. 40.7%, respectively,
P
< 0.0001). In multivariate analysis LDH maintained significant prognostic capacity in OS, PFS and RI. These findings in AML, validated in an independent cohort, suggest that LDH is a readily available tool that could be integrated into transplant risk assessments to aid decision-making and identify high-risk patients who may benefit from post-transplant pharmacological or cellular strategies.]]></description><subject>692/499</subject><subject>692/699/1541/1990</subject><subject>Acute myeloid leukemia</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Decision making</subject><subject>Health aspects</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic stem cells</subject><subject>Homografts</subject><subject>Humans</subject><subject>Internal Medicine</subject><subject>L-Lactate Dehydrogenase</subject><subject>Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute</subject><subject>Lymphoma</subject><subject>Lymphoma, Non-Hodgkin - therapy</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Multivariate analysis</subject><subject>Myeloid leukemia</subject><subject>Non-Hodgkin's lymphoma</subject><subject>Non-Hodgkin's lymphomas</subject><subject>Patient outcomes</subject><subject>Public Health</subject><subject>Retrospective Studies</subject><subject>Risk assessment</subject><subject>Risk groups</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>Survival</subject><subject>Testing</subject><subject>Transplantation</subject><subject>Transplantation Conditioning</subject><subject>Transplants & implants</subject><issn>0268-3369</issn><issn>1476-5365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kt2K1TAUhYsoznH0BbyQgCDeVPPX_FwOg3qEAW_0OqTt7mlm0qYm6cB5pnlJU8_oqBdCIIT9rbX3DquqXhL8jmCm3idOONY1pqTGhElZ60fVjnAp6oaJ5nG1w1SomjGhz6pnKV1jTDjHzdPqjHGiFFFkV93t3WFE3nbZZkA9jMc-hgPMNgGyGWU3AQoDsv3kUnJhRkOIyHq_MeA6NMJkc1iCg1xeOdo5Ld7OxW2DbUqhc8U5oRzQEoo2rfHW3VqPXCl3a2k6HcEH1yMP6w1MziI792gOc70P_eGmYP44LWOY7PPqyWB9ghf393n17eOHr5f7-urLp8-XF1d1xxnPdacxByX5QFXPiaZs0BZTpqVifaPblg8tpUSJ1mrCNNGDBTIURStlOUDZefX25LvE8H2FlE1ZvgNf9oKwJkMbLrSUDW0K-vof9DqscS7TFUqXJkIL8UAdrAfj5iGUj-o2U3MhFMFKCskK9eYPagTr85iCX7efTH-D9AR2MaQUYTBLdJONR0Ow2ZJhTskwJRnmZzKMLqJX95Ou7QT9b8mvKBSAnYBUSvMB4sMq_7H9AY9QxYY</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Geva, Mika</creator><creator>Pryce, Angharad</creator><creator>Shouval, Roni</creator><creator>Fein, Joshua A.</creator><creator>Danylesko, Ivetta</creator><creator>Shem-Tov, Noga</creator><creator>Yerushalmi, Ronit</creator><creator>Shimoni, Avichai</creator><creator>Szydlo, Richard</creator><creator>Pavlu, Jiri</creator><creator>Nagler, Arnon</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8420-8340</orcidid><orcidid>https://orcid.org/0000-0003-3473-3272</orcidid><orcidid>https://orcid.org/0000-0001-5441-1516</orcidid><orcidid>https://orcid.org/0000-0002-0763-1265</orcidid><orcidid>https://orcid.org/0000-0003-1102-8298</orcidid><orcidid>https://orcid.org/0000-0001-9827-8032</orcidid></search><sort><creationdate>20211101</creationdate><title>High lactate dehydrogenase at time of admission for allogeneic hematopoietic transplantation associates to poor survival in acute myeloid leukemia and non-Hodgkin lymphoma</title><author>Geva, Mika ; Pryce, Angharad ; Shouval, Roni ; Fein, Joshua A. ; Danylesko, Ivetta ; Shem-Tov, Noga ; Yerushalmi, Ronit ; Shimoni, Avichai ; Szydlo, Richard ; Pavlu, Jiri ; Nagler, Arnon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-c904e874f28d41923f9a0239783d59bb4fb22186ba913919fae1f4e8b77b77e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>692/499</topic><topic>692/699/1541/1990</topic><topic>Acute myeloid leukemia</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Decision making</topic><topic>Health aspects</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Hematopoietic stem cells</topic><topic>Homografts</topic><topic>Humans</topic><topic>Internal Medicine</topic><topic>L-Lactate Dehydrogenase</topic><topic>Lactate dehydrogenase</topic><topic>Lactic acid</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute</topic><topic>Lymphoma</topic><topic>Lymphoma, Non-Hodgkin - therapy</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Multivariate analysis</topic><topic>Myeloid leukemia</topic><topic>Non-Hodgkin's lymphoma</topic><topic>Non-Hodgkin's lymphomas</topic><topic>Patient outcomes</topic><topic>Public Health</topic><topic>Retrospective Studies</topic><topic>Risk assessment</topic><topic>Risk groups</topic><topic>Stem cell transplantation</topic><topic>Stem Cells</topic><topic>Survival</topic><topic>Testing</topic><topic>Transplantation</topic><topic>Transplantation Conditioning</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Geva, Mika</creatorcontrib><creatorcontrib>Pryce, Angharad</creatorcontrib><creatorcontrib>Shouval, Roni</creatorcontrib><creatorcontrib>Fein, Joshua A.</creatorcontrib><creatorcontrib>Danylesko, Ivetta</creatorcontrib><creatorcontrib>Shem-Tov, Noga</creatorcontrib><creatorcontrib>Yerushalmi, Ronit</creatorcontrib><creatorcontrib>Shimoni, Avichai</creatorcontrib><creatorcontrib>Szydlo, Richard</creatorcontrib><creatorcontrib>Pavlu, Jiri</creatorcontrib><creatorcontrib>Nagler, Arnon</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Bone marrow transplantation (Basingstoke)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Geva, Mika</au><au>Pryce, Angharad</au><au>Shouval, Roni</au><au>Fein, Joshua A.</au><au>Danylesko, Ivetta</au><au>Shem-Tov, Noga</au><au>Yerushalmi, Ronit</au><au>Shimoni, Avichai</au><au>Szydlo, Richard</au><au>Pavlu, Jiri</au><au>Nagler, Arnon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High lactate dehydrogenase at time of admission for allogeneic hematopoietic transplantation associates to poor survival in acute myeloid leukemia and non-Hodgkin lymphoma</atitle><jtitle>Bone marrow transplantation (Basingstoke)</jtitle><stitle>Bone Marrow Transplant</stitle><addtitle>Bone Marrow Transplant</addtitle><date>2021-11-01</date><risdate>2021</risdate><volume>56</volume><issue>11</issue><spage>2690</spage><epage>2696</epage><pages>2690-2696</pages><issn>0268-3369</issn><eissn>1476-5365</eissn><abstract><![CDATA[Risk stratification is important for balancing potential risks and benefits of allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. We retrospectively studied 1119 patients undergoing allogenic-HSCT in a single center for five hematological indications assessing the prognostic role of LDH at admission for survival (OS), progression-free survival (PFS), relapse incidence (RI), and nonrelapse mortality (NRM). In non-Hodgkin lymphoma (NHL) and acute myeloid leukemia (AML), higher than median LDH had an adverse effect on survival. The prognostic significance was strongest in AML, with higher LDH levels having lower 1-and 3-year survival 69.2% vs. 50.8%,
P
< 0.001 and 51.9% vs. 39.2%,
P
< 0.001, respectively, reduced 1-and 3-year PFS 62.4% vs. 42.1%,
P
< 0.001 48% vs. 35.2%,
P
< 0.001, respectively, higher cumulative incidence of 1-and 3-year NRM 11% vs. 17.3%,
p
= 0.01 and 15.7% vs. 19.6%,
P
= 0.04, and higher 1-and 3-year relapse incidence (RI) 26.7% vs. 40.7%,
p
< .0001 36.2% vs. 40.7%, respectively,
P
< 0.0001). In multivariate analysis LDH maintained significant prognostic capacity in OS, PFS and RI. These findings in AML, validated in an independent cohort, suggest that LDH is a readily available tool that could be integrated into transplant risk assessments to aid decision-making and identify high-risk patients who may benefit from post-transplant pharmacological or cellular strategies.]]></abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34188181</pmid><doi>10.1038/s41409-021-01377-9</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-8420-8340</orcidid><orcidid>https://orcid.org/0000-0003-3473-3272</orcidid><orcidid>https://orcid.org/0000-0001-5441-1516</orcidid><orcidid>https://orcid.org/0000-0002-0763-1265</orcidid><orcidid>https://orcid.org/0000-0003-1102-8298</orcidid><orcidid>https://orcid.org/0000-0001-9827-8032</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0268-3369 |
| ispartof | Bone marrow transplantation (Basingstoke), 2021-11, Vol.56 (11), p.2690-2696 |
| issn | 0268-3369 1476-5365 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2546977525 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 692/499 692/699/1541/1990 Acute myeloid leukemia Care and treatment Cell Biology Decision making Health aspects Hematology Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic stem cells Homografts Humans Internal Medicine L-Lactate Dehydrogenase Lactate dehydrogenase Lactic acid Leukemia Leukemia, Myeloid, Acute Lymphoma Lymphoma, Non-Hodgkin - therapy Medicine Medicine & Public Health Multivariate analysis Myeloid leukemia Non-Hodgkin's lymphoma Non-Hodgkin's lymphomas Patient outcomes Public Health Retrospective Studies Risk assessment Risk groups Stem cell transplantation Stem Cells Survival Testing Transplantation Transplantation Conditioning Transplants & implants |
| title | High lactate dehydrogenase at time of admission for allogeneic hematopoietic transplantation associates to poor survival in acute myeloid leukemia and non-Hodgkin lymphoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T21%3A06%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20lactate%20dehydrogenase%20at%20time%20of%20admission%20for%20allogeneic%20hematopoietic%20transplantation%20associates%20to%20poor%20survival%20in%20acute%20myeloid%20leukemia%20and%20non-Hodgkin%20lymphoma&rft.jtitle=Bone%20marrow%20transplantation%20(Basingstoke)&rft.au=Geva,%20Mika&rft.date=2021-11-01&rft.volume=56&rft.issue=11&rft.spage=2690&rft.epage=2696&rft.pages=2690-2696&rft.issn=0268-3369&rft.eissn=1476-5365&rft_id=info:doi/10.1038/s41409-021-01377-9&rft_dat=%3Cgale_proqu%3EA681087673%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2591866966&rft_id=info:pmid/34188181&rft_galeid=A681087673&rfr_iscdi=true |