Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis
•In a Center for International Blood and Marrow Transplant Research registry study, the rates of fungal infections (FI) and the impact of FI on mortality after haploidentical (Haplo) or matched sibling (Sib) donor hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (C...
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| creator | Papanicolaou, Genovefa A. Chen, Min He, Naya Martens, Michael J. Kim, Soyoung Batista, Marjorie V. Bhatt, Neel S. Hematti, Peiman Hill, Joshua A. Liu, Hongtao Nathan, Sunita Seftel, Matthew D. Sharma, Akshay Waller, Edmund K. Wingard, John R. Young, Jo-Anne H. Dandoy, Christopher E. Perales, Miguel-Angel Chemaly, Roy F. Riches, Marcie Ustun, Celalettin |
| description | •In a Center for International Blood and Marrow Transplant Research registry study, the rates of fungal infections (FI) and the impact of FI on mortality after haploidentical (Haplo) or matched sibling (Sib) donor hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (Cy) were compared with Sib donor HCT using calcineurin inhibitor (CNI)-based GVHD prophylaxis.•Overall, rates of FI by day 180 post-HCT in HaploCy, SibCy, and SibCNI ranged from 1.9% to 5.2% for FI caused by yeast and from 1.7% to 3.7% for FI caused by mold.•Compared with SibCNI, rates of FI from yeast were higher for HaploCy but not for SibCy, and rates of FI from mold were higher in both HaploCy and SibCy.•In multivariable analyses, the presence of FI was associated with increased risk of mortality at 2 years post-HCT in all 3 cohorts.
Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes.
Patients who underwent their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome and received a related haploidentical transplant with PTCy (HaploCy; n = 757) or a Sib transplant with PTCy (SibCy; n = 403) or CNI (SibCNI; n = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as cumulative incidence with death as the competing risk. The associations of FI with overall survival, transplant-related mortality, chronic GVHD, and relapse at 2 years post-HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model.
By day 180 post-HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI recipients developed ≥1 FI (P < .001). The cumulative incidence of yeast FI was 5.2% (99% confidence interval [CI], 3.3% to 7.3%) for HaploCy, 2.2% (99% CI, .7% to 4 |
| doi_str_mv | 10.1016/j.jtct.2023.09.017 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2870992184</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2666636723015567</els_id><sourcerecordid>2870992184</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3157-92a24e08362c3fdeb50127b812bb581ad7e8b5103c0d2584b7b390e56919205a3</originalsourceid><addsrcrecordid>eNp9kUFv1DAQhSMEolXpH-CAfOSS7djexAnist3S7kpFVKicLceZsF4ldrC9hf3zqM5uQRUHTh573nsz1pdlbynMKNDyYjvbRh1nDBifQT0DKl5kp6wsy7zkpXj5rD7JzkPYAgCbc6AcXmcnXAhRgIDT7PfaatOi1UiUbcl6GJWOxHXkeme_q56sbYc6GmcDMZbcuRDze69sGHtlo5oaZLnXvRs3LowbNaSs_FIFbMmNV13MH9CHXchXyUiuTMDUInc-yfe9-mXCYehKjb2blohGp5ErHFR0ozOY7mSJfU_-GfmBLNK7jehJ53zaMVX20En2y9659pD7WXnvfj4zk6-YNvB6QxZJuQ8mvMledaoPeP50nmXfrj_dL1f57Zeb9XJxm2tOC5HXTLE5QsVLpnnXYlMAZaKpKGuaoqKqFVg1BQWuoWVFNW9Ew2vAoqxpzaBQ_Cx7f8wdvfuxwxDlYIJOX1MW3S5IVgmoa0areZKyo1R7F4LHTo7eDMrvJQU5oZdbOaGXE3oJtUzok-ndU_6uGbD9a_kDOgk-HgWYfvlg0MugzYS9NT4Blq0z_8t_BNE3xcc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2870992184</pqid></control><display><type>article</type><title>Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Papanicolaou, Genovefa A. ; Chen, Min ; He, Naya ; Martens, Michael J. ; Kim, Soyoung ; Batista, Marjorie V. ; Bhatt, Neel S. ; Hematti, Peiman ; Hill, Joshua A. ; Liu, Hongtao ; Nathan, Sunita ; Seftel, Matthew D. ; Sharma, Akshay ; Waller, Edmund K. ; Wingard, John R. ; Young, Jo-Anne H. ; Dandoy, Christopher E. ; Perales, Miguel-Angel ; Chemaly, Roy F. ; Riches, Marcie ; Ustun, Celalettin</creator><creatorcontrib>Papanicolaou, Genovefa A. ; Chen, Min ; He, Naya ; Martens, Michael J. ; Kim, Soyoung ; Batista, Marjorie V. ; Bhatt, Neel S. ; Hematti, Peiman ; Hill, Joshua A. ; Liu, Hongtao ; Nathan, Sunita ; Seftel, Matthew D. ; Sharma, Akshay ; Waller, Edmund K. ; Wingard, John R. ; Young, Jo-Anne H. ; Dandoy, Christopher E. ; Perales, Miguel-Angel ; Chemaly, Roy F. ; Riches, Marcie ; Ustun, Celalettin</creatorcontrib><description>•In a Center for International Blood and Marrow Transplant Research registry study, the rates of fungal infections (FI) and the impact of FI on mortality after haploidentical (Haplo) or matched sibling (Sib) donor hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (Cy) were compared with Sib donor HCT using calcineurin inhibitor (CNI)-based GVHD prophylaxis.•Overall, rates of FI by day 180 post-HCT in HaploCy, SibCy, and SibCNI ranged from 1.9% to 5.2% for FI caused by yeast and from 1.7% to 3.7% for FI caused by mold.•Compared with SibCNI, rates of FI from yeast were higher for HaploCy but not for SibCy, and rates of FI from mold were higher in both HaploCy and SibCy.•In multivariable analyses, the presence of FI was associated with increased risk of mortality at 2 years post-HCT in all 3 cohorts.
Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes.
Patients who underwent their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome and received a related haploidentical transplant with PTCy (HaploCy; n = 757) or a Sib transplant with PTCy (SibCy; n = 403) or CNI (SibCNI; n = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as cumulative incidence with death as the competing risk. The associations of FI with overall survival, transplant-related mortality, chronic GVHD, and relapse at 2 years post-HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model.
By day 180 post-HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI recipients developed ≥1 FI (P < .001). The cumulative incidence of yeast FI was 5.2% (99% confidence interval [CI], 3.3% to 7.3%) for HaploCy, 2.2% (99% CI, .7% to 4.5%) for SibCy, and 1.9% (99% CI, 1.1% to 2.9%) for SibCNI (P = .001), and that of mold FI was 2.9% (99% CI, 1.5% to 4.7%), 3.7% (99% CI, 91.7% to 6.6%), and 1.7% (99% CI, 1.0% to 2.6%), respectively (P = .040). FI was associated with an increased risk of death, with an adjusted hazard ratio (HR) of 4.06 (99% CI, 2.2 to 7.6) for HaploCy, 4.7 (99% CI, 2.0 to 11.0) for SibCy, and 3.4 (99% CI, 1.8 to 6.4) for SibCNI compared with SibCNI without FI (P < .0001 for all). Similar associations were noted for transplantation-related mortality. FI did not impact rates of relapse or chronic GVHD.
Rates of FI by day 180 ranged between 1.9% and 5.2% for yeast FI and from 1.7% to 3.7% for mold FI across the 3 cohorts. The use of PTCy was associated with higher rates of yeast FI only in HaploHCT and with mold FI in both HaploHCT and SibHCT. The presence of FI by day 180 was associated with increased risk for overall mortality and transplant-related mortality at 2 years regardless of donor type or PTCy use. Although rates of FI were low with PTCy, FI is associated with an increased risk of death, underscoring the need for improved management strategies.</description><identifier>ISSN: 2666-6367</identifier><identifier>EISSN: 2666-6367</identifier><identifier>DOI: 10.1016/j.jtct.2023.09.017</identifier><identifier>PMID: 37775070</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Calcineurin Inhibitors - therapeutic use ; Cyclophosphamide - therapeutic use ; Fungal infection ; Graft versus host disease ; Graft vs Host Disease - drug therapy ; Graft vs Host Disease - epidemiology ; Graft vs Host Disease - prevention & control ; Haploidentical hematopoietic cell transplantation ; Hematopoietic Stem Cell Transplantation - adverse effects ; Humans ; Incidence ; Mortality ; Mycoses - drug therapy ; Mycoses - epidemiology ; Mycoses - prevention & control ; Post-transplantation cyclophosphamide ; Recurrence ; Saccharomyces cerevisiae</subject><ispartof>Transplantation and cellular therapy, 2024-01, Vol.30 (1), p.114.e1-114.e16</ispartof><rights>2023 The American Society for Transplantation and Cellular Therapy</rights><rights>Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3157-92a24e08362c3fdeb50127b812bb581ad7e8b5103c0d2584b7b390e56919205a3</citedby><cites>FETCH-LOGICAL-c3157-92a24e08362c3fdeb50127b812bb581ad7e8b5103c0d2584b7b390e56919205a3</cites><orcidid>0000-0003-1404-0575 ; 0000-0002-0277-3088 ; 0000-0001-7920-4265 ; 0000-0003-3281-2081 ; 0000-0003-4182-341X ; 0000-0001-7478-5398 ; 0000-0003-0816-6729 ; 0000-0003-0717-0873 ; 0000-0002-2891-079X ; 0000-0001-5836-4497 ; 0000-0003-2033-1125 ; 0000-0002-3190-7807 ; 0000-0002-5910-4571 ; 0000-0003-3799-681X ; 0000-0001-6896-6213</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37775070$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Papanicolaou, Genovefa A.</creatorcontrib><creatorcontrib>Chen, Min</creatorcontrib><creatorcontrib>He, Naya</creatorcontrib><creatorcontrib>Martens, Michael J.</creatorcontrib><creatorcontrib>Kim, Soyoung</creatorcontrib><creatorcontrib>Batista, Marjorie V.</creatorcontrib><creatorcontrib>Bhatt, Neel S.</creatorcontrib><creatorcontrib>Hematti, Peiman</creatorcontrib><creatorcontrib>Hill, Joshua A.</creatorcontrib><creatorcontrib>Liu, Hongtao</creatorcontrib><creatorcontrib>Nathan, Sunita</creatorcontrib><creatorcontrib>Seftel, Matthew D.</creatorcontrib><creatorcontrib>Sharma, Akshay</creatorcontrib><creatorcontrib>Waller, Edmund K.</creatorcontrib><creatorcontrib>Wingard, John R.</creatorcontrib><creatorcontrib>Young, Jo-Anne H.</creatorcontrib><creatorcontrib>Dandoy, Christopher E.</creatorcontrib><creatorcontrib>Perales, Miguel-Angel</creatorcontrib><creatorcontrib>Chemaly, Roy F.</creatorcontrib><creatorcontrib>Riches, Marcie</creatorcontrib><creatorcontrib>Ustun, Celalettin</creatorcontrib><title>Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis</title><title>Transplantation and cellular therapy</title><addtitle>Transplant Cell Ther</addtitle><description>•In a Center for International Blood and Marrow Transplant Research registry study, the rates of fungal infections (FI) and the impact of FI on mortality after haploidentical (Haplo) or matched sibling (Sib) donor hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (Cy) were compared with Sib donor HCT using calcineurin inhibitor (CNI)-based GVHD prophylaxis.•Overall, rates of FI by day 180 post-HCT in HaploCy, SibCy, and SibCNI ranged from 1.9% to 5.2% for FI caused by yeast and from 1.7% to 3.7% for FI caused by mold.•Compared with SibCNI, rates of FI from yeast were higher for HaploCy but not for SibCy, and rates of FI from mold were higher in both HaploCy and SibCy.•In multivariable analyses, the presence of FI was associated with increased risk of mortality at 2 years post-HCT in all 3 cohorts.
Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes.
Patients who underwent their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome and received a related haploidentical transplant with PTCy (HaploCy; n = 757) or a Sib transplant with PTCy (SibCy; n = 403) or CNI (SibCNI; n = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as cumulative incidence with death as the competing risk. The associations of FI with overall survival, transplant-related mortality, chronic GVHD, and relapse at 2 years post-HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model.
By day 180 post-HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI recipients developed ≥1 FI (P < .001). The cumulative incidence of yeast FI was 5.2% (99% confidence interval [CI], 3.3% to 7.3%) for HaploCy, 2.2% (99% CI, .7% to 4.5%) for SibCy, and 1.9% (99% CI, 1.1% to 2.9%) for SibCNI (P = .001), and that of mold FI was 2.9% (99% CI, 1.5% to 4.7%), 3.7% (99% CI, 91.7% to 6.6%), and 1.7% (99% CI, 1.0% to 2.6%), respectively (P = .040). FI was associated with an increased risk of death, with an adjusted hazard ratio (HR) of 4.06 (99% CI, 2.2 to 7.6) for HaploCy, 4.7 (99% CI, 2.0 to 11.0) for SibCy, and 3.4 (99% CI, 1.8 to 6.4) for SibCNI compared with SibCNI without FI (P < .0001 for all). Similar associations were noted for transplantation-related mortality. FI did not impact rates of relapse or chronic GVHD.
Rates of FI by day 180 ranged between 1.9% and 5.2% for yeast FI and from 1.7% to 3.7% for mold FI across the 3 cohorts. The use of PTCy was associated with higher rates of yeast FI only in HaploHCT and with mold FI in both HaploHCT and SibHCT. The presence of FI by day 180 was associated with increased risk for overall mortality and transplant-related mortality at 2 years regardless of donor type or PTCy use. Although rates of FI were low with PTCy, FI is associated with an increased risk of death, underscoring the need for improved management strategies.</description><subject>Calcineurin Inhibitors - therapeutic use</subject><subject>Cyclophosphamide - therapeutic use</subject><subject>Fungal infection</subject><subject>Graft versus host disease</subject><subject>Graft vs Host Disease - drug therapy</subject><subject>Graft vs Host Disease - epidemiology</subject><subject>Graft vs Host Disease - prevention & control</subject><subject>Haploidentical hematopoietic cell transplantation</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Humans</subject><subject>Incidence</subject><subject>Mortality</subject><subject>Mycoses - drug therapy</subject><subject>Mycoses - epidemiology</subject><subject>Mycoses - prevention & control</subject><subject>Post-transplantation cyclophosphamide</subject><subject>Recurrence</subject><subject>Saccharomyces cerevisiae</subject><issn>2666-6367</issn><issn>2666-6367</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFv1DAQhSMEolXpH-CAfOSS7djexAnist3S7kpFVKicLceZsF4ldrC9hf3zqM5uQRUHTh573nsz1pdlbynMKNDyYjvbRh1nDBifQT0DKl5kp6wsy7zkpXj5rD7JzkPYAgCbc6AcXmcnXAhRgIDT7PfaatOi1UiUbcl6GJWOxHXkeme_q56sbYc6GmcDMZbcuRDze69sGHtlo5oaZLnXvRs3LowbNaSs_FIFbMmNV13MH9CHXchXyUiuTMDUInc-yfe9-mXCYehKjb2blohGp5ErHFR0ozOY7mSJfU_-GfmBLNK7jehJ53zaMVX20En2y9659pD7WXnvfj4zk6-YNvB6QxZJuQ8mvMledaoPeP50nmXfrj_dL1f57Zeb9XJxm2tOC5HXTLE5QsVLpnnXYlMAZaKpKGuaoqKqFVg1BQWuoWVFNW9Ew2vAoqxpzaBQ_Cx7f8wdvfuxwxDlYIJOX1MW3S5IVgmoa0areZKyo1R7F4LHTo7eDMrvJQU5oZdbOaGXE3oJtUzok-ndU_6uGbD9a_kDOgk-HgWYfvlg0MugzYS9NT4Blq0z_8t_BNE3xcc</recordid><startdate>202401</startdate><enddate>202401</enddate><creator>Papanicolaou, Genovefa A.</creator><creator>Chen, Min</creator><creator>He, Naya</creator><creator>Martens, Michael J.</creator><creator>Kim, Soyoung</creator><creator>Batista, Marjorie V.</creator><creator>Bhatt, Neel S.</creator><creator>Hematti, Peiman</creator><creator>Hill, Joshua A.</creator><creator>Liu, Hongtao</creator><creator>Nathan, Sunita</creator><creator>Seftel, Matthew D.</creator><creator>Sharma, Akshay</creator><creator>Waller, Edmund K.</creator><creator>Wingard, John R.</creator><creator>Young, Jo-Anne H.</creator><creator>Dandoy, Christopher E.</creator><creator>Perales, Miguel-Angel</creator><creator>Chemaly, Roy F.</creator><creator>Riches, Marcie</creator><creator>Ustun, Celalettin</creator><general>Elsevier Inc</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>7X8</scope><orcidid>https://orcid.org/0000-0003-1404-0575</orcidid><orcidid>https://orcid.org/0000-0002-0277-3088</orcidid><orcidid>https://orcid.org/0000-0001-7920-4265</orcidid><orcidid>https://orcid.org/0000-0003-3281-2081</orcidid><orcidid>https://orcid.org/0000-0003-4182-341X</orcidid><orcidid>https://orcid.org/0000-0001-7478-5398</orcidid><orcidid>https://orcid.org/0000-0003-0816-6729</orcidid><orcidid>https://orcid.org/0000-0003-0717-0873</orcidid><orcidid>https://orcid.org/0000-0002-2891-079X</orcidid><orcidid>https://orcid.org/0000-0001-5836-4497</orcidid><orcidid>https://orcid.org/0000-0003-2033-1125</orcidid><orcidid>https://orcid.org/0000-0002-3190-7807</orcidid><orcidid>https://orcid.org/0000-0002-5910-4571</orcidid><orcidid>https://orcid.org/0000-0003-3799-681X</orcidid><orcidid>https://orcid.org/0000-0001-6896-6213</orcidid></search><sort><creationdate>202401</creationdate><title>Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis</title><author>Papanicolaou, Genovefa A. ; Chen, Min ; He, Naya ; Martens, Michael J. ; Kim, Soyoung ; Batista, Marjorie V. ; Bhatt, Neel S. ; Hematti, Peiman ; Hill, Joshua A. ; Liu, Hongtao ; Nathan, Sunita ; Seftel, Matthew D. ; Sharma, Akshay ; Waller, Edmund K. ; Wingard, John R. ; Young, Jo-Anne H. ; Dandoy, Christopher E. ; Perales, Miguel-Angel ; Chemaly, Roy F. ; Riches, Marcie ; Ustun, Celalettin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3157-92a24e08362c3fdeb50127b812bb581ad7e8b5103c0d2584b7b390e56919205a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Calcineurin Inhibitors - therapeutic use</topic><topic>Cyclophosphamide - therapeutic use</topic><topic>Fungal infection</topic><topic>Graft versus host disease</topic><topic>Graft vs Host Disease - drug therapy</topic><topic>Graft vs Host Disease - epidemiology</topic><topic>Graft vs Host Disease - prevention & control</topic><topic>Haploidentical hematopoietic cell transplantation</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Humans</topic><topic>Incidence</topic><topic>Mortality</topic><topic>Mycoses - drug therapy</topic><topic>Mycoses - epidemiology</topic><topic>Mycoses - prevention & control</topic><topic>Post-transplantation cyclophosphamide</topic><topic>Recurrence</topic><topic>Saccharomyces cerevisiae</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Papanicolaou, Genovefa A.</creatorcontrib><creatorcontrib>Chen, Min</creatorcontrib><creatorcontrib>He, Naya</creatorcontrib><creatorcontrib>Martens, Michael J.</creatorcontrib><creatorcontrib>Kim, Soyoung</creatorcontrib><creatorcontrib>Batista, Marjorie V.</creatorcontrib><creatorcontrib>Bhatt, Neel S.</creatorcontrib><creatorcontrib>Hematti, Peiman</creatorcontrib><creatorcontrib>Hill, Joshua A.</creatorcontrib><creatorcontrib>Liu, Hongtao</creatorcontrib><creatorcontrib>Nathan, Sunita</creatorcontrib><creatorcontrib>Seftel, Matthew D.</creatorcontrib><creatorcontrib>Sharma, Akshay</creatorcontrib><creatorcontrib>Waller, Edmund K.</creatorcontrib><creatorcontrib>Wingard, John R.</creatorcontrib><creatorcontrib>Young, Jo-Anne H.</creatorcontrib><creatorcontrib>Dandoy, Christopher E.</creatorcontrib><creatorcontrib>Perales, Miguel-Angel</creatorcontrib><creatorcontrib>Chemaly, Roy F.</creatorcontrib><creatorcontrib>Riches, Marcie</creatorcontrib><creatorcontrib>Ustun, Celalettin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation and cellular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Papanicolaou, Genovefa A.</au><au>Chen, Min</au><au>He, Naya</au><au>Martens, Michael J.</au><au>Kim, Soyoung</au><au>Batista, Marjorie V.</au><au>Bhatt, Neel S.</au><au>Hematti, Peiman</au><au>Hill, Joshua A.</au><au>Liu, Hongtao</au><au>Nathan, Sunita</au><au>Seftel, Matthew D.</au><au>Sharma, Akshay</au><au>Waller, Edmund K.</au><au>Wingard, John R.</au><au>Young, Jo-Anne H.</au><au>Dandoy, Christopher E.</au><au>Perales, Miguel-Angel</au><au>Chemaly, Roy F.</au><au>Riches, Marcie</au><au>Ustun, Celalettin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis</atitle><jtitle>Transplantation and cellular therapy</jtitle><addtitle>Transplant Cell Ther</addtitle><date>2024-01</date><risdate>2024</risdate><volume>30</volume><issue>1</issue><spage>114.e1</spage><epage>114.e16</epage><pages>114.e1-114.e16</pages><issn>2666-6367</issn><eissn>2666-6367</eissn><abstract>•In a Center for International Blood and Marrow Transplant Research registry study, the rates of fungal infections (FI) and the impact of FI on mortality after haploidentical (Haplo) or matched sibling (Sib) donor hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (Cy) were compared with Sib donor HCT using calcineurin inhibitor (CNI)-based GVHD prophylaxis.•Overall, rates of FI by day 180 post-HCT in HaploCy, SibCy, and SibCNI ranged from 1.9% to 5.2% for FI caused by yeast and from 1.7% to 3.7% for FI caused by mold.•Compared with SibCNI, rates of FI from yeast were higher for HaploCy but not for SibCy, and rates of FI from mold were higher in both HaploCy and SibCy.•In multivariable analyses, the presence of FI was associated with increased risk of mortality at 2 years post-HCT in all 3 cohorts.
Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes.
Patients who underwent their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome and received a related haploidentical transplant with PTCy (HaploCy; n = 757) or a Sib transplant with PTCy (SibCy; n = 403) or CNI (SibCNI; n = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as cumulative incidence with death as the competing risk. The associations of FI with overall survival, transplant-related mortality, chronic GVHD, and relapse at 2 years post-HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model.
By day 180 post-HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI recipients developed ≥1 FI (P < .001). The cumulative incidence of yeast FI was 5.2% (99% confidence interval [CI], 3.3% to 7.3%) for HaploCy, 2.2% (99% CI, .7% to 4.5%) for SibCy, and 1.9% (99% CI, 1.1% to 2.9%) for SibCNI (P = .001), and that of mold FI was 2.9% (99% CI, 1.5% to 4.7%), 3.7% (99% CI, 91.7% to 6.6%), and 1.7% (99% CI, 1.0% to 2.6%), respectively (P = .040). FI was associated with an increased risk of death, with an adjusted hazard ratio (HR) of 4.06 (99% CI, 2.2 to 7.6) for HaploCy, 4.7 (99% CI, 2.0 to 11.0) for SibCy, and 3.4 (99% CI, 1.8 to 6.4) for SibCNI compared with SibCNI without FI (P < .0001 for all). Similar associations were noted for transplantation-related mortality. FI did not impact rates of relapse or chronic GVHD.
Rates of FI by day 180 ranged between 1.9% and 5.2% for yeast FI and from 1.7% to 3.7% for mold FI across the 3 cohorts. The use of PTCy was associated with higher rates of yeast FI only in HaploHCT and with mold FI in both HaploHCT and SibHCT. The presence of FI by day 180 was associated with increased risk for overall mortality and transplant-related mortality at 2 years regardless of donor type or PTCy use. Although rates of FI were low with PTCy, FI is associated with an increased risk of death, underscoring the need for improved management strategies.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37775070</pmid><doi>10.1016/j.jtct.2023.09.017</doi><orcidid>https://orcid.org/0000-0003-1404-0575</orcidid><orcidid>https://orcid.org/0000-0002-0277-3088</orcidid><orcidid>https://orcid.org/0000-0001-7920-4265</orcidid><orcidid>https://orcid.org/0000-0003-3281-2081</orcidid><orcidid>https://orcid.org/0000-0003-4182-341X</orcidid><orcidid>https://orcid.org/0000-0001-7478-5398</orcidid><orcidid>https://orcid.org/0000-0003-0816-6729</orcidid><orcidid>https://orcid.org/0000-0003-0717-0873</orcidid><orcidid>https://orcid.org/0000-0002-2891-079X</orcidid><orcidid>https://orcid.org/0000-0001-5836-4497</orcidid><orcidid>https://orcid.org/0000-0003-2033-1125</orcidid><orcidid>https://orcid.org/0000-0002-3190-7807</orcidid><orcidid>https://orcid.org/0000-0002-5910-4571</orcidid><orcidid>https://orcid.org/0000-0003-3799-681X</orcidid><orcidid>https://orcid.org/0000-0001-6896-6213</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2666-6367 |
| ispartof | Transplantation and cellular therapy, 2024-01, Vol.30 (1), p.114.e1-114.e16 |
| issn | 2666-6367 2666-6367 |
| language | eng |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Calcineurin Inhibitors - therapeutic use Cyclophosphamide - therapeutic use Fungal infection Graft versus host disease Graft vs Host Disease - drug therapy Graft vs Host Disease - epidemiology Graft vs Host Disease - prevention & control Haploidentical hematopoietic cell transplantation Hematopoietic Stem Cell Transplantation - adverse effects Humans Incidence Mortality Mycoses - drug therapy Mycoses - epidemiology Mycoses - prevention & control Post-transplantation cyclophosphamide Recurrence Saccharomyces cerevisiae |
| title | Incidence and Impact of Fungal Infections in Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis and Haploidentical Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Analysis |
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