Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans
The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliter...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2006-12, Vol.114 (24), p.2679-2684 |
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| creator | MIYAMOTO, Koji NISHIGAMI, Kazuhiro NAKATANI, Takeshi NONOGI, Hiroshi TAKESHITA, Satoshi NAGAYA, Noritoshi AKUTSU, Koichi CHIKU, Masaaki KAMEI, Masataka SOMA, Toshihiro MIYATA, Shigeki HIGASHI, Masahiro TANAKA, Ryoichi |
| description | The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans.
Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684+/-549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1+/-0.7 to 1.5+/-1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year.
In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment. |
| doi_str_mv | 10.1161/CIRCULATIONAHA.106.644203 |
| format | Article |
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Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684+/-549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1+/-0.7 to 1.5+/-1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year.
In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.106.644203</identifier><identifier>PMID: 17145986</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adult ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood vessels and receptors ; Bone Marrow Transplantation - adverse effects ; Cardiology. Vascular system ; Cardiovascular system ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Female ; Follow-Up Studies ; Fundamental and applied biological sciences. Psychology ; Humans ; Leukocytes, Mononuclear - transplantation ; Male ; Medical sciences ; Middle Aged ; Neovascularization, Physiologic ; Pharmacology. Drug treatments ; Pilot Projects ; Thromboangiitis Obliterans - diagnosis ; Thromboangiitis Obliterans - mortality ; Thromboangiitis Obliterans - physiopathology ; Thromboangiitis Obliterans - surgery ; Transplantation, Autologous ; Vasodilator agents. Cerebral vasodilators ; Vertebrates: cardiovascular system</subject><ispartof>Circulation (New York, N.Y.), 2006-12, Vol.114 (24), p.2679-2684</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-f83eca9f0d89ab3fb5392bfb9bc59addeaa184251b20ef533180cd1e2b9c32683</citedby><cites>FETCH-LOGICAL-c439t-f83eca9f0d89ab3fb5392bfb9bc59addeaa184251b20ef533180cd1e2b9c32683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18360739$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17145986$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MIYAMOTO, Koji</creatorcontrib><creatorcontrib>NISHIGAMI, Kazuhiro</creatorcontrib><creatorcontrib>NAKATANI, Takeshi</creatorcontrib><creatorcontrib>NONOGI, Hiroshi</creatorcontrib><creatorcontrib>TAKESHITA, Satoshi</creatorcontrib><creatorcontrib>NAGAYA, Noritoshi</creatorcontrib><creatorcontrib>AKUTSU, Koichi</creatorcontrib><creatorcontrib>CHIKU, Masaaki</creatorcontrib><creatorcontrib>KAMEI, Masataka</creatorcontrib><creatorcontrib>SOMA, Toshihiro</creatorcontrib><creatorcontrib>MIYATA, Shigeki</creatorcontrib><creatorcontrib>HIGASHI, Masahiro</creatorcontrib><creatorcontrib>TANAKA, Ryoichi</creatorcontrib><title>Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans.
Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684+/-549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1+/-0.7 to 1.5+/-1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year.
In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood vessels and receptors</subject><subject>Bone Marrow Transplantation - adverse effects</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Leukocytes, Mononuclear - transplantation</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neovascularization, Physiologic</subject><subject>Pharmacology. Drug treatments</subject><subject>Pilot Projects</subject><subject>Thromboangiitis Obliterans - diagnosis</subject><subject>Thromboangiitis Obliterans - mortality</subject><subject>Thromboangiitis Obliterans - physiopathology</subject><subject>Thromboangiitis Obliterans - surgery</subject><subject>Transplantation, Autologous</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><subject>Vertebrates: cardiovascular system</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1P5CAch4lxo6O7X2GDB7115KWl5TiZ7OokE002zrkBCsqGQgUa482PLpOZxHgiwPN_-T0AXGG0xJjh2_Xm33q3XT1tHh9W96slRmzJ6pogegIWuCF1VTeUn4IFQohXLSXkHFyk9L9cGW2bM3COW1w3vGML8LHz0lk_6AFO1oUMU56HdxgMFHMOLjyHOcEchU-TEz6LbIPf_8rgNRxFjOENjsEHPyunRYRKO5eg9XAqqPY5wTebX2B-iWGUQfhna7NNMJShWe_b_gQ_jHBJ_zqel2D398_T-r7aPt5t1qttpWrKc2U6qpXgBg0dF5IaWRISaSSXquFiGLQQuKtJgyVB2jSU4g6pAWsiuaKEdfQS3Bz6TjG8zjrlfrRpv63wumTsWUdoy5q2gPwAqhhSitr0U7Ql6XuPUb_X33_XX55Zf9Bfan8fh8xy1MNX5dF3Aa6PgEhKOFMMKJu-uI4y1FJOPwE6zJRr</recordid><startdate>20061212</startdate><enddate>20061212</enddate><creator>MIYAMOTO, Koji</creator><creator>NISHIGAMI, Kazuhiro</creator><creator>NAKATANI, Takeshi</creator><creator>NONOGI, Hiroshi</creator><creator>TAKESHITA, Satoshi</creator><creator>NAGAYA, Noritoshi</creator><creator>AKUTSU, Koichi</creator><creator>CHIKU, Masaaki</creator><creator>KAMEI, Masataka</creator><creator>SOMA, Toshihiro</creator><creator>MIYATA, Shigeki</creator><creator>HIGASHI, Masahiro</creator><creator>TANAKA, Ryoichi</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>20061212</creationdate><title>Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans</title><author>MIYAMOTO, Koji ; NISHIGAMI, Kazuhiro ; NAKATANI, Takeshi ; NONOGI, Hiroshi ; TAKESHITA, Satoshi ; NAGAYA, Noritoshi ; AKUTSU, Koichi ; CHIKU, Masaaki ; KAMEI, Masataka ; SOMA, Toshihiro ; MIYATA, Shigeki ; HIGASHI, Masahiro ; TANAKA, Ryoichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-f83eca9f0d89ab3fb5392bfb9bc59addeaa184251b20ef533180cd1e2b9c32683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood vessels and receptors</topic><topic>Bone Marrow Transplantation - adverse effects</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular system</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Leukocytes, Mononuclear - transplantation</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neovascularization, Physiologic</topic><topic>Pharmacology. Drug treatments</topic><topic>Pilot Projects</topic><topic>Thromboangiitis Obliterans - diagnosis</topic><topic>Thromboangiitis Obliterans - mortality</topic><topic>Thromboangiitis Obliterans - physiopathology</topic><topic>Thromboangiitis Obliterans - surgery</topic><topic>Transplantation, Autologous</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MIYAMOTO, Koji</creatorcontrib><creatorcontrib>NISHIGAMI, Kazuhiro</creatorcontrib><creatorcontrib>NAKATANI, Takeshi</creatorcontrib><creatorcontrib>NONOGI, Hiroshi</creatorcontrib><creatorcontrib>TAKESHITA, Satoshi</creatorcontrib><creatorcontrib>NAGAYA, Noritoshi</creatorcontrib><creatorcontrib>AKUTSU, Koichi</creatorcontrib><creatorcontrib>CHIKU, Masaaki</creatorcontrib><creatorcontrib>KAMEI, Masataka</creatorcontrib><creatorcontrib>SOMA, Toshihiro</creatorcontrib><creatorcontrib>MIYATA, Shigeki</creatorcontrib><creatorcontrib>HIGASHI, Masahiro</creatorcontrib><creatorcontrib>TANAKA, Ryoichi</creatorcontrib><collection>Pascal-Francis</collection><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>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MIYAMOTO, Koji</au><au>NISHIGAMI, Kazuhiro</au><au>NAKATANI, Takeshi</au><au>NONOGI, Hiroshi</au><au>TAKESHITA, Satoshi</au><au>NAGAYA, Noritoshi</au><au>AKUTSU, Koichi</au><au>CHIKU, Masaaki</au><au>KAMEI, Masataka</au><au>SOMA, Toshihiro</au><au>MIYATA, Shigeki</au><au>HIGASHI, Masahiro</au><au>TANAKA, Ryoichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2006-12-12</date><risdate>2006</risdate><volume>114</volume><issue>24</issue><spage>2679</spage><epage>2684</epage><pages>2679-2684</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans.
Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684+/-549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1+/-0.7 to 1.5+/-1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year.
In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>17145986</pmid><doi>10.1161/CIRCULATIONAHA.106.644203</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2006-12, Vol.114 (24), p.2679-2684 |
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| source | MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | Adult Biological and medical sciences Blood and lymphatic vessels Blood vessels and receptors Bone Marrow Transplantation - adverse effects Cardiology. Vascular system Cardiovascular system Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Female Follow-Up Studies Fundamental and applied biological sciences. Psychology Humans Leukocytes, Mononuclear - transplantation Male Medical sciences Middle Aged Neovascularization, Physiologic Pharmacology. Drug treatments Pilot Projects Thromboangiitis Obliterans - diagnosis Thromboangiitis Obliterans - mortality Thromboangiitis Obliterans - physiopathology Thromboangiitis Obliterans - surgery Transplantation, Autologous Vasodilator agents. Cerebral vasodilators Vertebrates: cardiovascular system |
| title | Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans |
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