Conversion from calcineurin inhibitors to sirolimus in transplant‐associated thrombotic microangiopathy
Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a specific complication of allogeneic hematopoietic cell transplantation with a multifactorial etiology. There is little evidence published regarding the efficacy and factors influencing the outcome of substitution of calcineurin inhibitor...
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| Veröffentlicht in: | Clinical transplantation 2021-02, Vol.35 (2), p.e14180-n/a |
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| creator | Kanunnikov, Mikhail M. Rakhmanova, Zhemal Z. Levkovsky, Nikita V. Vafina, Aliya I. Goloshapov, Oleg V. Shchegoleva, Tatiana S. Vlasova, Julia J. Paina, Olesya V. Morozova, Elena V. Zubarovskaya, Ludmilla Kulagin, Alexander D. Moiseev, Ivan |
| description | Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a specific complication of allogeneic hematopoietic cell transplantation with a multifactorial etiology. There is little evidence published regarding the efficacy and factors influencing the outcome of substitution of calcineurin inhibitors (CNIs) with other agentsas a widely accepted practice in this disorder; however, there are limited data on the options for immunosuppression manipulation (ISM). In our study, we retrospectively analyzed outcomes of 45 patients with TA‐TMA with ISM and substitution either with steroids (steroid group) or anmTOR inhibitor sirolimus (sirolimus group). In our study, sirolimus was associated with significantly better 1‐year overall survival (HR 0.3, 95% CI 0.13‐0.7, p = .004) and faster time to normalization of LDH (HR 2.2, 95% CI 0.99‐4.99, p = .044). Replacing CNIs with sirolimus could be an effective option in patients with TA‐TMA. A multicenter confirmatory study of CNIs replacement with sirolimus is justified. |
| doi_str_mv | 10.1111/ctr.14180 |
| format | Article |
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There is little evidence published regarding the efficacy and factors influencing the outcome of substitution of calcineurin inhibitors (CNIs) with other agentsas a widely accepted practice in this disorder; however, there are limited data on the options for immunosuppression manipulation (ISM). In our study, we retrospectively analyzed outcomes of 45 patients with TA‐TMA with ISM and substitution either with steroids (steroid group) or anmTOR inhibitor sirolimus (sirolimus group). In our study, sirolimus was associated with significantly better 1‐year overall survival (HR 0.3, 95% CI 0.13‐0.7, p = .004) and faster time to normalization of LDH (HR 2.2, 95% CI 0.99‐4.99, p = .044). Replacing CNIs with sirolimus could be an effective option in patients with TA‐TMA. A multicenter confirmatory study of CNIs replacement with sirolimus is justified.</description><identifier>ISSN: 0902-0063</identifier><identifier>EISSN: 1399-0012</identifier><identifier>DOI: 10.1111/ctr.14180</identifier><identifier>PMID: 33258122</identifier><language>eng</language><publisher>Denmark</publisher><subject>calcineurin inhibitors ; Calcineurin Inhibitors - therapeutic use ; Hematopoietic Stem Cell Transplantation - adverse effects ; Humans ; immunosuppression manipulation ; Retrospective Studies ; sirolimus ; Sirolimus - therapeutic use ; TA‐TMA ; Thrombotic Microangiopathies - drug therapy ; Thrombotic Microangiopathies - etiology ; thrombotic microangiopathy</subject><ispartof>Clinical transplantation, 2021-02, Vol.35 (2), p.e14180-n/a</ispartof><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3250-8317e334fcd0cdbec6585959e3068cac8a1439b0eedd35acccc13b941acefd0c3</citedby><cites>FETCH-LOGICAL-c3250-8317e334fcd0cdbec6585959e3068cac8a1439b0eedd35acccc13b941acefd0c3</cites><orcidid>0000-0002-1460-330X ; 0000-0002-4332-0114</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fctr.14180$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fctr.14180$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33258122$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kanunnikov, Mikhail M.</creatorcontrib><creatorcontrib>Rakhmanova, Zhemal Z.</creatorcontrib><creatorcontrib>Levkovsky, Nikita V.</creatorcontrib><creatorcontrib>Vafina, Aliya I.</creatorcontrib><creatorcontrib>Goloshapov, Oleg V.</creatorcontrib><creatorcontrib>Shchegoleva, Tatiana S.</creatorcontrib><creatorcontrib>Vlasova, Julia J.</creatorcontrib><creatorcontrib>Paina, Olesya V.</creatorcontrib><creatorcontrib>Morozova, Elena V.</creatorcontrib><creatorcontrib>Zubarovskaya, Ludmilla</creatorcontrib><creatorcontrib>Kulagin, Alexander D.</creatorcontrib><creatorcontrib>Moiseev, Ivan</creatorcontrib><title>Conversion from calcineurin inhibitors to sirolimus in transplant‐associated thrombotic microangiopathy</title><title>Clinical transplantation</title><addtitle>Clin Transplant</addtitle><description>Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a specific complication of allogeneic hematopoietic cell transplantation with a multifactorial etiology. There is little evidence published regarding the efficacy and factors influencing the outcome of substitution of calcineurin inhibitors (CNIs) with other agentsas a widely accepted practice in this disorder; however, there are limited data on the options for immunosuppression manipulation (ISM). In our study, we retrospectively analyzed outcomes of 45 patients with TA‐TMA with ISM and substitution either with steroids (steroid group) or anmTOR inhibitor sirolimus (sirolimus group). In our study, sirolimus was associated with significantly better 1‐year overall survival (HR 0.3, 95% CI 0.13‐0.7, p = .004) and faster time to normalization of LDH (HR 2.2, 95% CI 0.99‐4.99, p = .044). Replacing CNIs with sirolimus could be an effective option in patients with TA‐TMA. A multicenter confirmatory study of CNIs replacement with sirolimus is justified.</description><subject>calcineurin inhibitors</subject><subject>Calcineurin Inhibitors - therapeutic use</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Humans</subject><subject>immunosuppression manipulation</subject><subject>Retrospective Studies</subject><subject>sirolimus</subject><subject>Sirolimus - therapeutic use</subject><subject>TA‐TMA</subject><subject>Thrombotic Microangiopathies - drug therapy</subject><subject>Thrombotic Microangiopathies - etiology</subject><subject>thrombotic microangiopathy</subject><issn>0902-0063</issn><issn>1399-0012</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1KxDAURoMozji68AUkS110JmnaTruU4h8MCDKuQ5reOpE2qUmqzM5H8Bl9EqMd3Xk3N1xODh8fQqeUzGmYhfR2ThOakz00pawoIkJovI-mpCBxeGdsgo6cew7XjGbpIZowFqc5jeMpUqXRr2CdMho31nRYilYqDYNVGiu9UZXyxjrsDXbKmlZ1gwt37K3Qrm-F9p_vH8I5I5XwUGO_CZLKeCVxp6Q1Qj8p0wu_2R6jg0a0Dk52e4Yer6_W5W20ur-5Ky9XkQyhSJQzugTGkkbWRNYVyCzN0yItgJEsl0LmgiasqAhAXbNUyDCUVUVChYQmfGEzdD56e2teBnCed8pJaENWMIPjcZJlhKVLSgN6MaIhqHMWGt5b1Qm75ZTw72Z5aJb_NBvYs512qDqo_8jfKgOwGIE31cL2fxMv1w-j8guK8Idr</recordid><startdate>202102</startdate><enddate>202102</enddate><creator>Kanunnikov, Mikhail M.</creator><creator>Rakhmanova, Zhemal Z.</creator><creator>Levkovsky, Nikita V.</creator><creator>Vafina, Aliya I.</creator><creator>Goloshapov, Oleg V.</creator><creator>Shchegoleva, Tatiana S.</creator><creator>Vlasova, Julia J.</creator><creator>Paina, Olesya V.</creator><creator>Morozova, Elena V.</creator><creator>Zubarovskaya, Ludmilla</creator><creator>Kulagin, Alexander D.</creator><creator>Moiseev, Ivan</creator><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/0000-0002-1460-330X</orcidid><orcidid>https://orcid.org/0000-0002-4332-0114</orcidid></search><sort><creationdate>202102</creationdate><title>Conversion from calcineurin inhibitors to sirolimus in transplant‐associated thrombotic microangiopathy</title><author>Kanunnikov, Mikhail M. ; Rakhmanova, Zhemal Z. ; Levkovsky, Nikita V. ; Vafina, Aliya I. ; Goloshapov, Oleg V. ; Shchegoleva, Tatiana S. ; Vlasova, Julia J. ; Paina, Olesya V. ; Morozova, Elena V. ; Zubarovskaya, Ludmilla ; Kulagin, Alexander D. ; Moiseev, Ivan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3250-8317e334fcd0cdbec6585959e3068cac8a1439b0eedd35acccc13b941acefd0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>calcineurin inhibitors</topic><topic>Calcineurin Inhibitors - therapeutic use</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Humans</topic><topic>immunosuppression manipulation</topic><topic>Retrospective Studies</topic><topic>sirolimus</topic><topic>Sirolimus - therapeutic use</topic><topic>TA‐TMA</topic><topic>Thrombotic Microangiopathies - drug therapy</topic><topic>Thrombotic Microangiopathies - etiology</topic><topic>thrombotic microangiopathy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kanunnikov, Mikhail M.</creatorcontrib><creatorcontrib>Rakhmanova, Zhemal Z.</creatorcontrib><creatorcontrib>Levkovsky, Nikita V.</creatorcontrib><creatorcontrib>Vafina, Aliya I.</creatorcontrib><creatorcontrib>Goloshapov, Oleg V.</creatorcontrib><creatorcontrib>Shchegoleva, Tatiana S.</creatorcontrib><creatorcontrib>Vlasova, Julia J.</creatorcontrib><creatorcontrib>Paina, Olesya V.</creatorcontrib><creatorcontrib>Morozova, Elena V.</creatorcontrib><creatorcontrib>Zubarovskaya, Ludmilla</creatorcontrib><creatorcontrib>Kulagin, Alexander D.</creatorcontrib><creatorcontrib>Moiseev, Ivan</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>Clinical transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kanunnikov, Mikhail M.</au><au>Rakhmanova, Zhemal Z.</au><au>Levkovsky, Nikita V.</au><au>Vafina, Aliya I.</au><au>Goloshapov, Oleg V.</au><au>Shchegoleva, Tatiana S.</au><au>Vlasova, Julia J.</au><au>Paina, Olesya V.</au><au>Morozova, Elena V.</au><au>Zubarovskaya, Ludmilla</au><au>Kulagin, Alexander D.</au><au>Moiseev, Ivan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Conversion from calcineurin inhibitors to sirolimus in transplant‐associated thrombotic microangiopathy</atitle><jtitle>Clinical transplantation</jtitle><addtitle>Clin Transplant</addtitle><date>2021-02</date><risdate>2021</risdate><volume>35</volume><issue>2</issue><spage>e14180</spage><epage>n/a</epage><pages>e14180-n/a</pages><issn>0902-0063</issn><eissn>1399-0012</eissn><abstract>Transplant‐associated thrombotic microangiopathy (TA‐TMA) is a specific complication of allogeneic hematopoietic cell transplantation with a multifactorial etiology. There is little evidence published regarding the efficacy and factors influencing the outcome of substitution of calcineurin inhibitors (CNIs) with other agentsas a widely accepted practice in this disorder; however, there are limited data on the options for immunosuppression manipulation (ISM). In our study, we retrospectively analyzed outcomes of 45 patients with TA‐TMA with ISM and substitution either with steroids (steroid group) or anmTOR inhibitor sirolimus (sirolimus group). In our study, sirolimus was associated with significantly better 1‐year overall survival (HR 0.3, 95% CI 0.13‐0.7, p = .004) and faster time to normalization of LDH (HR 2.2, 95% CI 0.99‐4.99, p = .044). Replacing CNIs with sirolimus could be an effective option in patients with TA‐TMA. 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| subjects | calcineurin inhibitors Calcineurin Inhibitors - therapeutic use Hematopoietic Stem Cell Transplantation - adverse effects Humans immunosuppression manipulation Retrospective Studies sirolimus Sirolimus - therapeutic use TA‐TMA Thrombotic Microangiopathies - drug therapy Thrombotic Microangiopathies - etiology thrombotic microangiopathy |
| title | Conversion from calcineurin inhibitors to sirolimus in transplant‐associated thrombotic microangiopathy |
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