{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:38:31Z","timestamp":1773286711714,"version":"3.50.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2002,3,12]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Background<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            The proportion of cardiac transplant recipients with preexisting sensitization to HLA alloantigens has been increasing. Sensitization prolongs duration to obtaining a donor and predicts poorer long-term allograft survival because of increased risk of cellular rejections. We investigated the effect of cyclophosphamide pulse therapy in sensitized cardiac allograft recipients.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Methods and Results<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Pretransplant and posttransplant outcomes were compared between 88 cardiac allograft recipients at risk for sensitization and 26 sensitized recipients treated with intravenous cyclophosphamide pulse therapy together with intravenous immune globulin before transplant and as part of a cyclosporine-based triple immunosuppressive regimen after transplant. Preformed IgG anti-HLA antibodies predicted longer duration to transplantation, earlier cellular rejection, and 2.7-fold higher cumulative rejection frequency (\n            <jats:italic>P<\/jats:italic>\n            =0.002). Before transplant, cyclophosphamide reduced waiting time and mortality to levels in nonsensitized patients. After transplant, cyclophosphamide prevented induction of IgG anti-HLA class II antibodies and interleukin-2 receptor\u2013positive T-cell outgrowth from biopsy sites (both\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01), prolonged the rejection-free interval (\n            <jats:italic>P<\/jats:italic>\n            =0.009), and reduced cumulative rejections to levels in nonsensitized patients (\n            <jats:italic>P<\/jats:italic>\n            =0.003). By multivariable analysis, the risk of rejection was 3.7-fold higher in patients treated with mycophenolate mofetil than patients treated with cyclophosphamide (\n            <jats:italic>P<\/jats:italic>\n            =0.019). There were no differences in infectious or other significant complications.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Conclusions<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Immunosuppression incorporating intravenous cyclophosphamide before and after transplantation is safe and highly effective in sensitized cardiac transplant recipients. When used after transplantation as part of triple immunosuppression, cyclophosphamide is superior to mycophenolate mofetil in reducing rejection. The mechanism may involve prevention of diversification of the recipient immune response to donor HLA class II molecules.\n          <\/jats:p>","DOI":"10.1161\/hc1002.105128","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:16:07Z","timestamp":1027898167000},"page":"1214-1219","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Intravenous Pulse Administration of Cyclophosphamide Is an Effective and Safe Treatment for Sensitized Cardiac Allograft Recipients"],"prefix":"10.1161","volume":"105","author":[{"given":"Silviu","family":"Itescu","sequence":"first","affiliation":[{"name":"From the College of Physicians and Surgeons of Columbia University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Burke","sequence":"additional","affiliation":[{"name":"From the College of Physicians and Surgeons of Columbia University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Lietz","sequence":"additional","affiliation":[{"name":"From the College of Physicians and Surgeons of Columbia University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranjit","family":"John","sequence":"additional","affiliation":[{"name":"From the College of Physicians and Surgeons of Columbia University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Mancini","sequence":"additional","affiliation":[{"name":"From the College of Physicians and Surgeons of Columbia University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Michler","sequence":"additional","affiliation":[{"name":"From the College of Physicians and Surgeons of Columbia University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Rose","sequence":"additional","affiliation":[{"name":"From the College of Physicians and Surgeons of Columbia University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"Oz","sequence":"additional","affiliation":[{"name":"From the College of Physicians and Surgeons of Columbia University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niloo","family":"Edwards","sequence":"additional","affiliation":[{"name":"From the College of Physicians and Surgeons of Columbia University, New York, NY."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","first-page":"272","volume":"50","year":"1993","unstructured":"Joysey VC, Tissue typing, heart and heart-lung transplantation. Br J Biomed Sci. 1993; 50: 272\u2013276.","journal-title":"Br J Biomed Sci"},{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199210000-00017"},{"key":"e_1_3_1_3_2","first-page":"921","volume":"10","year":"1991","unstructured":"Lavee J, Kormos RL, Duquesnoy RJ, et al. Influence of panel-reactive antibody and lymphocytotoxic cross-match on survival after heart transplantation. J Heart Lung Transplant. 1991; 10: 921\u2013930.","journal-title":"J Heart Lung Transplant"},{"key":"e_1_3_1_4_2","first-page":"203","volume":"106","year":"1989","unstructured":"Rose EA, Smith CR, Petrossian GA, et al. Humoral immune responses after cardiac transplantation: correlation with fatal rejection and graft atherosclerosis. Surgery. 1989; 106: 203\u2013208.","journal-title":"Surgery"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.98.8.786"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(97)00807-2"},{"key":"e_1_3_1_7_2","first-page":"876","volume":"17","year":"1998","unstructured":"Moazami N, Itescu S, Williams M, et al. Platelet transfusions are associated with the development of anti-major histocompatibility complex class I antibodies in patients with left ventricular assist support. J Heart Lung Transplant. 1998; 17: 876\u2013880.","journal-title":"J Heart Lung Transplant"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)10359-8"},{"key":"e_1_3_1_9_2","first-page":"2750","volume":"26","year":"1994","unstructured":"Hode EE, Klingman LL, Koo AP, et al. Pretransplant removal of anti-HLA antibodies by plasmapharesis and continued suppression on cyclosporine-based therapy after heart-kidney transplant. Transplant Proc. 1994; 26: 2750\u20132751.","journal-title":"Transplant Proc"},{"key":"e_1_3_1_10_2","first-page":"1366","volume":"107","year":"1994","unstructured":"Ruiz JC, de Francisco AL, Vazquez de Prada JA, et al. Successful heart transplantation after anti-HLA antibody removal with protein-A immunoadsorption in a hyperimmunized patient. J Thorac Cardiovasc Surg. 1994; 107: 1366\u20131367.","journal-title":"J Thorac Cardiovasc Surg"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199308000-00015"},{"key":"e_1_3_1_12_2","first-page":"553","volume":"57","year":"1995","unstructured":"Tyan DB, Li VA, Czer L, et al. Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. Transplantation. 1995; 57: 553\u2013562.","journal-title":"Transplantation"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112922"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780170404"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-116-6-488"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-91-2-221"},{"key":"e_1_3_1_17_2","first-page":"568","volume":"1","year":"1972","unstructured":"Fairley KF, Barrie JU, Johnson W. Sterility and testicular atrophy related to cyclophosphamide therapy. Lancet. 1972; 1: 568\u2013569.","journal-title":"Lancet"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198603063141004"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1177\/096120339500400205"},{"key":"e_1_3_1_20_2","first-page":"1835","volume":"4","year":"1998","unstructured":"Haubitz M, Schellong S, Gobel U, et al. Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective randomized study. Arthritis Rheum. 1998; 4: 1835\u20131844.","journal-title":"Arthritis Rheum"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)09475-6"},{"key":"e_1_3_1_22_2","first-page":"272","volume":"9","year":"1990","unstructured":"Billingham ME. Dilemma of variety of histopathologic grading systems for acute cardiac allograft rejection by endomyocardial biopsy. J Heart Transplant. 1990; 9: 272\u2013276.","journal-title":"J Heart Transplant"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1989.10478873"},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","volume":"34","year":"1972","unstructured":"Cox DR. Regression models and life tables. J R Stat Soc. 1972; 34: 187\u2013220.","journal-title":"J R Stat Soc"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)90563-V"},{"key":"e_1_3_1_27_2","first-page":"678.","volume":"342","year":"1993","unstructured":"Lam L, Whitsett CF, McNicholl JM, et al. Immunologically active proteins in intravenous immunoglobulin. Lancet. 1993; 342: 678.","journal-title":"Lancet"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118488"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.100.suppl_2.Ii-229"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.5.2013"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.6.1643"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118898"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(96)80012-4"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90274-O"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-2498(98)00062-X"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/hc1002.105128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T01:35:06Z","timestamp":1715650506000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/hc1002.105128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,3,12]]},"references-count":35,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2002,3,12]]}},"alternative-id":["10.1161\/hc1002.105128"],"URL":"https:\/\/doi.org\/10.1161\/hc1002.105128","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,3,12]]},"assertion":[{"value":"2002-02-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}