Early defibrotide therapy and risk factors for post‐transplant veno‐occlusive disease/sinusoidal obstruction syndrome in childhood
Background Veno‐occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life‐threatening complications of hematopoietic cell transplantation (HCT). Methods We studied the impact of early defibrotide (DF) therapy on the outcomes of pediatric patients with VOD/SOS after tran...
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| Veröffentlicht in: | Pediatric blood & cancer 2024-12, Vol.71 (12), p.e31331-n/a |
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| creator | Goto, Hironori Oba, Utako Ueda, Tamaki Yamamoto, Shunsuke Inoue, Masataka Shimo, Yu Yokoyama, Satomi Takase, Yusuke Kato, Wakako Suenobu, Souichi Ihara, Kenji Koga, Yuhki Ohga, Shouichi |
| description | Background
Veno‐occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life‐threatening complications of hematopoietic cell transplantation (HCT).
Methods
We studied the impact of early defibrotide (DF) therapy on the outcomes of pediatric patients with VOD/SOS after transplantation, focusing on recent immunotherapies. A total of 111 pediatric patients who underwent HCT for malignant disease between February 2017 and March 2023 at Kyushu University Hospital were included.
Results
Among 111 patients of less than 20 years of age who underwent HCT for malignancy at a single institution between 2017 and 2023, VOD/SOS occurred in 25 (23%) patients. VOD/SOS developed more frequently in the post‐DF era (2020–2023, n = 58) than in the pre‐DF era (31% vs. 13%, p = .04). The proportion of patients with relapsed/refractory acute lymphoblastic leukemia (ALL) was higher in the post‐DF era than in the pre‐DF era (44% vs. 8%, p = .04). Early DF therapy that was started at two European Society for Blood and Marrow Transplantation diagnostic criteria reduced the severity of VOD/SOS (p |
| doi_str_mv | 10.1002/pbc.31331 |
| format | Article |
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Veno‐occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life‐threatening complications of hematopoietic cell transplantation (HCT).
Methods
We studied the impact of early defibrotide (DF) therapy on the outcomes of pediatric patients with VOD/SOS after transplantation, focusing on recent immunotherapies. A total of 111 pediatric patients who underwent HCT for malignant disease between February 2017 and March 2023 at Kyushu University Hospital were included.
Results
Among 111 patients of less than 20 years of age who underwent HCT for malignancy at a single institution between 2017 and 2023, VOD/SOS occurred in 25 (23%) patients. VOD/SOS developed more frequently in the post‐DF era (2020–2023, n = 58) than in the pre‐DF era (31% vs. 13%, p = .04). The proportion of patients with relapsed/refractory acute lymphoblastic leukemia (ALL) was higher in the post‐DF era than in the pre‐DF era (44% vs. 8%, p = .04). Early DF therapy that was started at two European Society for Blood and Marrow Transplantation diagnostic criteria reduced the severity of VOD/SOS (p < .01) in comparison to non‐early therapy started at less than two criteria. A multivariate analysis indicated that a history of cytokine release syndrome (odds ratio [OR] = 10.4, p = .01) and juvenile myelomonocytic leukemia (OR = 8.98, p = .04), but not an endothelial activation and stress index (EASIX) score of greater than 0.85, were independent risk factors for VOD/SOS.
Conclusions
Early DF therapy improves the severity and survival outcomes of post‐transplant VOD/SOS in children. However, its incidence is increasing in the era of immunotherapy for progressive diseases.</description><identifier>ISSN: 1545-5009</identifier><identifier>ISSN: 1545-5017</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.31331</identifier><identifier>PMID: 39289887</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Acute lymphoblastic leukemia ; Adolescent ; Adult ; Bone marrow transplantation ; Child ; Child, Preschool ; Childhood ; Children ; cytokine release syndrome ; defibrotide ; Disease ; Female ; Fibrinolytic Agents - adverse effects ; Fibrinolytic Agents - therapeutic use ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic stem cells ; Hepatic Veno-Occlusive Disease - etiology ; Humans ; Immunotherapy ; Infant ; Leukemia ; Lymphatic leukemia ; Male ; Malignancy ; Multivariate analysis ; Myelomonocytic leukemia ; Patients ; Pediatrics ; Polydeoxyribonucleotides - therapeutic use ; Prognosis ; Retrospective Studies ; Risk Factors ; Stem cell transplantation ; Survival Rate ; Transplants & implants ; VOD/SOS ; Young Adult</subject><ispartof>Pediatric blood & cancer, 2024-12, Vol.71 (12), p.e31331-n/a</ispartof><rights>2024 The Author(s). published by Wiley Periodicals LLC.</rights><rights>2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2781-5251f873c84dc0372e7c0d76b74437e6db8b226e5fd0ee4b6b337b7e579554793</cites><orcidid>0000-0003-2912-1335 ; 0000-0003-2120-3440 ; 0000-0002-6266-1088 ; 0000-0002-8831-1991 ; 0009-0008-9409-2802 ; 0000-0003-2216-8368 ; 0000-0002-5313-7161</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%2Fpbc.31331$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.31331$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39289887$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goto, Hironori</creatorcontrib><creatorcontrib>Oba, Utako</creatorcontrib><creatorcontrib>Ueda, Tamaki</creatorcontrib><creatorcontrib>Yamamoto, Shunsuke</creatorcontrib><creatorcontrib>Inoue, Masataka</creatorcontrib><creatorcontrib>Shimo, Yu</creatorcontrib><creatorcontrib>Yokoyama, Satomi</creatorcontrib><creatorcontrib>Takase, Yusuke</creatorcontrib><creatorcontrib>Kato, Wakako</creatorcontrib><creatorcontrib>Suenobu, Souichi</creatorcontrib><creatorcontrib>Ihara, Kenji</creatorcontrib><creatorcontrib>Koga, Yuhki</creatorcontrib><creatorcontrib>Ohga, Shouichi</creatorcontrib><title>Early defibrotide therapy and risk factors for post‐transplant veno‐occlusive disease/sinusoidal obstruction syndrome in childhood</title><title>Pediatric blood & cancer</title><addtitle>Pediatr Blood Cancer</addtitle><description>Background
Veno‐occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life‐threatening complications of hematopoietic cell transplantation (HCT).
Methods
We studied the impact of early defibrotide (DF) therapy on the outcomes of pediatric patients with VOD/SOS after transplantation, focusing on recent immunotherapies. A total of 111 pediatric patients who underwent HCT for malignant disease between February 2017 and March 2023 at Kyushu University Hospital were included.
Results
Among 111 patients of less than 20 years of age who underwent HCT for malignancy at a single institution between 2017 and 2023, VOD/SOS occurred in 25 (23%) patients. VOD/SOS developed more frequently in the post‐DF era (2020–2023, n = 58) than in the pre‐DF era (31% vs. 13%, p = .04). The proportion of patients with relapsed/refractory acute lymphoblastic leukemia (ALL) was higher in the post‐DF era than in the pre‐DF era (44% vs. 8%, p = .04). Early DF therapy that was started at two European Society for Blood and Marrow Transplantation diagnostic criteria reduced the severity of VOD/SOS (p < .01) in comparison to non‐early therapy started at less than two criteria. A multivariate analysis indicated that a history of cytokine release syndrome (odds ratio [OR] = 10.4, p = .01) and juvenile myelomonocytic leukemia (OR = 8.98, p = .04), but not an endothelial activation and stress index (EASIX) score of greater than 0.85, were independent risk factors for VOD/SOS.
Conclusions
Early DF therapy improves the severity and survival outcomes of post‐transplant VOD/SOS in children. However, its incidence is increasing in the era of immunotherapy for progressive diseases.</description><subject>Acute lymphoblastic leukemia</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Bone marrow transplantation</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Childhood</subject><subject>Children</subject><subject>cytokine release syndrome</subject><subject>defibrotide</subject><subject>Disease</subject><subject>Female</subject><subject>Fibrinolytic Agents - adverse effects</subject><subject>Fibrinolytic Agents - therapeutic use</subject><subject>Follow-Up Studies</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hematopoietic stem cells</subject><subject>Hepatic Veno-Occlusive Disease - etiology</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Infant</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Male</subject><subject>Malignancy</subject><subject>Multivariate analysis</subject><subject>Myelomonocytic leukemia</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Polydeoxyribonucleotides - therapeutic use</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Risk Factors</subject><subject>Stem cell transplantation</subject><subject>Survival Rate</subject><subject>Transplants & implants</subject><subject>VOD/SOS</subject><subject>Young Adult</subject><issn>1545-5009</issn><issn>1545-5017</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp10btuFDEUBmALgUgIFLwAskQDxWZ9GY9nSrIKFykSFFCPfDmjdZi1Bx9P0HRU1DwjT4JhQwokKh9Zn36do5-Qp5ydc8bEdrbuXHIp-T1yylWjNopxff9uZv0JeYR4XWnLVPeQnMhedH3X6VPy_dLkaaUexmBzKsEDLXvIZl6piZ7mgJ_paFxJGemYMp0Tlp_ffpRsIs6TiYXeQEz1Jzk3LRhugPqAYBC2GOKCKXgz0WSx5MWVkCLFNfqcDkBDpG4fJr9PyT8mD0YzITy5fc_Ip9eXH3dvN1fv37zbvbraOKE7vlFC8bHT0nWNd0xqAdoxr1urm0ZqaL3trBAtqNEzgMa2VkptNSjdK9XoXp6RF8fcOacvC2AZDgEdTPUSSAsOkrO2aaUUotLn_9DrtORYt6uK1zzedqyql0flckLMMA5zDgeT14Gz4Xc5Qy1n-FNOtc9uExd7AH8n_7ZRwfYIvoYJ1v8nDR8udsfIXzxZnNM</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Goto, Hironori</creator><creator>Oba, Utako</creator><creator>Ueda, Tamaki</creator><creator>Yamamoto, Shunsuke</creator><creator>Inoue, Masataka</creator><creator>Shimo, Yu</creator><creator>Yokoyama, Satomi</creator><creator>Takase, Yusuke</creator><creator>Kato, Wakako</creator><creator>Suenobu, Souichi</creator><creator>Ihara, Kenji</creator><creator>Koga, Yuhki</creator><creator>Ohga, Shouichi</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><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>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2912-1335</orcidid><orcidid>https://orcid.org/0000-0003-2120-3440</orcidid><orcidid>https://orcid.org/0000-0002-6266-1088</orcidid><orcidid>https://orcid.org/0000-0002-8831-1991</orcidid><orcidid>https://orcid.org/0009-0008-9409-2802</orcidid><orcidid>https://orcid.org/0000-0003-2216-8368</orcidid><orcidid>https://orcid.org/0000-0002-5313-7161</orcidid></search><sort><creationdate>202412</creationdate><title>Early defibrotide therapy and risk factors for post‐transplant veno‐occlusive disease/sinusoidal obstruction syndrome in childhood</title><author>Goto, Hironori ; Oba, Utako ; Ueda, Tamaki ; Yamamoto, Shunsuke ; Inoue, Masataka ; Shimo, Yu ; Yokoyama, Satomi ; Takase, Yusuke ; Kato, Wakako ; Suenobu, Souichi ; Ihara, Kenji ; Koga, Yuhki ; Ohga, Shouichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2781-5251f873c84dc0372e7c0d76b74437e6db8b226e5fd0ee4b6b337b7e579554793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Bone marrow transplantation</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Childhood</topic><topic>Children</topic><topic>cytokine release syndrome</topic><topic>defibrotide</topic><topic>Disease</topic><topic>Female</topic><topic>Fibrinolytic Agents - adverse effects</topic><topic>Fibrinolytic Agents - therapeutic use</topic><topic>Follow-Up Studies</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Hematopoietic stem cells</topic><topic>Hepatic Veno-Occlusive Disease - etiology</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Infant</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Male</topic><topic>Malignancy</topic><topic>Multivariate analysis</topic><topic>Myelomonocytic leukemia</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Polydeoxyribonucleotides - therapeutic use</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Risk Factors</topic><topic>Stem cell transplantation</topic><topic>Survival Rate</topic><topic>Transplants & implants</topic><topic>VOD/SOS</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goto, Hironori</creatorcontrib><creatorcontrib>Oba, Utako</creatorcontrib><creatorcontrib>Ueda, Tamaki</creatorcontrib><creatorcontrib>Yamamoto, Shunsuke</creatorcontrib><creatorcontrib>Inoue, Masataka</creatorcontrib><creatorcontrib>Shimo, Yu</creatorcontrib><creatorcontrib>Yokoyama, Satomi</creatorcontrib><creatorcontrib>Takase, Yusuke</creatorcontrib><creatorcontrib>Kato, Wakako</creatorcontrib><creatorcontrib>Suenobu, Souichi</creatorcontrib><creatorcontrib>Ihara, Kenji</creatorcontrib><creatorcontrib>Koga, Yuhki</creatorcontrib><creatorcontrib>Ohga, Shouichi</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goto, Hironori</au><au>Oba, Utako</au><au>Ueda, Tamaki</au><au>Yamamoto, Shunsuke</au><au>Inoue, Masataka</au><au>Shimo, Yu</au><au>Yokoyama, Satomi</au><au>Takase, Yusuke</au><au>Kato, Wakako</au><au>Suenobu, Souichi</au><au>Ihara, Kenji</au><au>Koga, Yuhki</au><au>Ohga, Shouichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early defibrotide therapy and risk factors for post‐transplant veno‐occlusive disease/sinusoidal obstruction syndrome in childhood</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2024-12</date><risdate>2024</risdate><volume>71</volume><issue>12</issue><spage>e31331</spage><epage>n/a</epage><pages>e31331-n/a</pages><issn>1545-5009</issn><issn>1545-5017</issn><eissn>1545-5017</eissn><abstract>Background
Veno‐occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a life‐threatening complications of hematopoietic cell transplantation (HCT).
Methods
We studied the impact of early defibrotide (DF) therapy on the outcomes of pediatric patients with VOD/SOS after transplantation, focusing on recent immunotherapies. A total of 111 pediatric patients who underwent HCT for malignant disease between February 2017 and March 2023 at Kyushu University Hospital were included.
Results
Among 111 patients of less than 20 years of age who underwent HCT for malignancy at a single institution between 2017 and 2023, VOD/SOS occurred in 25 (23%) patients. VOD/SOS developed more frequently in the post‐DF era (2020–2023, n = 58) than in the pre‐DF era (31% vs. 13%, p = .04). The proportion of patients with relapsed/refractory acute lymphoblastic leukemia (ALL) was higher in the post‐DF era than in the pre‐DF era (44% vs. 8%, p = .04). Early DF therapy that was started at two European Society for Blood and Marrow Transplantation diagnostic criteria reduced the severity of VOD/SOS (p < .01) in comparison to non‐early therapy started at less than two criteria. A multivariate analysis indicated that a history of cytokine release syndrome (odds ratio [OR] = 10.4, p = .01) and juvenile myelomonocytic leukemia (OR = 8.98, p = .04), but not an endothelial activation and stress index (EASIX) score of greater than 0.85, were independent risk factors for VOD/SOS.
Conclusions
Early DF therapy improves the severity and survival outcomes of post‐transplant VOD/SOS in children. However, its incidence is increasing in the era of immunotherapy for progressive diseases.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>39289887</pmid><doi>10.1002/pbc.31331</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-2912-1335</orcidid><orcidid>https://orcid.org/0000-0003-2120-3440</orcidid><orcidid>https://orcid.org/0000-0002-6266-1088</orcidid><orcidid>https://orcid.org/0000-0002-8831-1991</orcidid><orcidid>https://orcid.org/0009-0008-9409-2802</orcidid><orcidid>https://orcid.org/0000-0003-2216-8368</orcidid><orcidid>https://orcid.org/0000-0002-5313-7161</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acute lymphoblastic leukemia Adolescent Adult Bone marrow transplantation Child Child, Preschool Childhood Children cytokine release syndrome defibrotide Disease Female Fibrinolytic Agents - adverse effects Fibrinolytic Agents - therapeutic use Follow-Up Studies Hematopoietic Stem Cell Transplantation - adverse effects Hematopoietic stem cells Hepatic Veno-Occlusive Disease - etiology Humans Immunotherapy Infant Leukemia Lymphatic leukemia Male Malignancy Multivariate analysis Myelomonocytic leukemia Patients Pediatrics Polydeoxyribonucleotides - therapeutic use Prognosis Retrospective Studies Risk Factors Stem cell transplantation Survival Rate Transplants & implants VOD/SOS Young Adult |
| title | Early defibrotide therapy and risk factors for post‐transplant veno‐occlusive disease/sinusoidal obstruction syndrome in childhood |
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