{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:21:34Z","timestamp":1788142894650,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,10,24]],"date-time":"2004-10-24T00:00:00Z","timestamp":1098576000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>6\u2010Thioguanine (TG) was recently studied to determine whether TG in maintenance therapy achieves better event free survival than 6\u2010mercaptopurine (MP) for standard risk acute lymphoblastic leukemia (ALL) on the clinical trial, CCG\u20101952 (5\/1996\u20131\/2000). Veno\u2010occlusive disease was previously recognized as a complication of TG on CCG\u20101952. We report a newly recognized pediatric complication of TG: splenomegaly and portal hypertension (PH) developing during maintenance or after completion of therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Twelve patients (3\u201310 years) had been randomized to receive a targeted dose of 50 mg\/m<jats:sup>2<\/jats:sup>\/day of TG during maintenance phases. Actual TG dose ranged from 25 to 77 mg\/m<jats:sup>2<\/jats:sup>\/day (median 34 mg\/m<jats:sup>2<\/jats:sup>\/day).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The initial patient, a boy who had marked thrombocytopenia and intermittent splenomegaly during maintenance therapy, was evaluated for persistent pancytopenia and progressive splenomegaly 3 months after completion of therapy. Dilated splenic vein and collaterals consistent with PH were documented by MRI\/MRA. Esophagogastroduodenoscopy found esophageal varices. Liver biopsy showed periportal fibrosis and marked dilatation of veins and venules. Of the other 12 patients, 9 patients studied had abnormal MRI\/MRAs with evidence of varices in 4. Eight patients had splenomegaly on physical examination. Liver biopsies in a girl after 3.3 courses of TG and a boy after 4.6 courses of TG showed periportal fibrosis and dilatation of venules and sinusoids and minimal focal fatty changes. Subsequent MRI\/MRAs have been stable or improved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The evaluations of these 12 patients suggest that treatment with TG causes injury to the liver leading to PH and that thrombocytopenia and splenomegaly are clinical hallmarks of this toxicity. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.20202","type":"journal-article","created":{"date-parts":[[2004,11,12]],"date-time":"2004-11-12T20:49:50Z","timestamp":1100292590000},"page":"226-231","source":"Crossref","is-referenced-by-count":46,"title":["Portal hypertension develops in a subset of children with standard risk acute lymphoblastic leukemia treated with oral 6\u2010thioguanine during maintenance therapy"],"prefix":"10.1002","volume":"44","author":[{"given":"Emmett H.","family":"Broxson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukund","family":"Dole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard F.","family":"Laya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Stork","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,24]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(94)90159-7"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1983.tb04255.x"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1993.311"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.00812.x"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1983.tb02178.x"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)92400-7"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-199302000-00010"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-85-5-578"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-96-1-58"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-96-6-788_1"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(08)80659-7"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91478-4"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.43.3.206"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1991.tb04520.x"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-199807000-00109"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04578.x"},{"key":"e_1_2_5_18_2","first-page":"36a","article-title":"Comparison of mercaptopurine with thioguanine and IT methotrexate with IT \u201cTriples\u201d in children with standard risk (SR) ALL: Results of CCG\u20101952","volume":"100","author":"Stork LC","year":"2002","journal-title":"Blood"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1993.311"},{"key":"e_1_2_5_20_2","first-page":"58","article-title":"for the COALL Study Group. Randomized comparison of 6 MP vs. 6TG in maintenance treatment of childhood ALL: Preliminary clinical results","volume":"93","author":"Harm D","year":"1996","journal-title":"Br J Hem"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5170.393"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-911X(199602)26:2<85::AID-MPO3>3.0.CO;2-Q"},{"key":"e_1_2_5_23_2","first-page":"256","article-title":"Role of endothelial cell injury in the spectrum of azathioprine\u2010induced liver disease after renal transplant: Light microscopy and ultrastructural observations","volume":"83","author":"Haboubi NY","year":"1888","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.171.2.2704798"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.176.4.1760891"},{"key":"e_1_2_5_26_2","first-page":"36a","article-title":"TG\u2010related VOD of liver in children with ALL: Report from UK Medical Research Council Trial ALL 97","volume":"100","author":"Vora AJ","year":"2002","journal-title":"Blood"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-23204"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpbc.20202","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.20202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:30:00Z","timestamp":1696897800000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.20202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10,24]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,3]]}},"alternative-id":["10.1002\/pbc.20202"],"URL":"https:\/\/doi.org\/10.1002\/pbc.20202","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10,24]]}}}