{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T21:39:40Z","timestamp":1774042780566,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,19]],"date-time":"2006-07-19T00:00:00Z","timestamp":1153267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> The treatment of relapsed adult acute lymphoblastic leukaemia (ALL) is frequently unsuccessful with current chemotherapy regimens, and often there is an overexpression of multidrug resistance (MDR)\u2010related proteins. Liposomal encapsulation makes daunorubicin (DNR) less sensitive to the efflux effect of P\u2010glycoprotein (PGP), and <jats:italic>in vitro<\/jats:italic> data indicate that liposomal\u2010encapsulated DNR (Daunoxome\u2010DNX) is more toxic than DNR against ALL cell lines. In this study, we assessed the <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> efficacy and toxicity of DNX plus cytarabine (Ara\u2010C) as reinduction chemotherapy in 25 relapsed ALL patients (pts). The expression of MDR\u2010related proteins (PGP, MRP1 and LRP) was also analysed. Of the 25 pts, 12 were males and 13 females; median age was 32\u2003yr (range 18\u201358). Six cases were ALL T and 19 ALL B; eight pts were Ph+ (32%), and nine Bcr\u2010Abl+ (36%). The expression of MDR\u2010related proteins, and DNR and DNX retention and induction of apoptosis in leukaemic cells were evaluated in all cases. Seventeen of 25 (68%) pts were at first relapse and eight (32%) at second or subsequent relapse. The DNX was given in a dose of 80\u2003mg\/m<jats:sup>2<\/jats:sup>\/d (days 1\u20133) in 11\/25 pts (44%) and in a dose of 100\u2003mg\/m<jats:sup>2<\/jats:sup>\/d (days 1\u20133) in 14\/25 pts (66%). In all pts, Ara\u2010C was administered in a dose of 2\u2003g\/m<jats:sup>2<\/jats:sup> (days 1\u20135). Twenty pts (80%) achieved a complete remission (CR) and two (8%) entered a partial remission (PR) for an overall response (OR) rate of 88% (22\/25), with a tolerable toxicity and without significant cardiotoxicity. Before the start of DNX therapy, 18\/25 (72%) cases overexpressed at least one MDR\u2010related protein compared with 9\/25 (36%) cases with MDR overexpression at diagnosis (<jats:italic>P<\/jats:italic>\u2003=\u20030.01). Taking into account the small number of cases, the response rate was not affected by MDR expression and the <jats:italic>in vitro<\/jats:italic> results also showed a higher uptake and apoptotic cell death by DNX compared with DNR. Twelve pts subsequently underwent allogeneic bone marrow transplantation (11 unrelated donor BMT, and one sibling BMT). The overall survival was 39% after 12\u2003months. These data show the efficacy (OR rate 88% and CR rate 80%) of DNX plus Ara\u2010C as reinduction therapy in very poor\u2010risk ALL pts and the response rate seems not to be affected by MDR overexpression. Moreover, the high rate of remissions and the good clinical tolerance in heavily pretreated pts suggest a promising role of DNX in ALL chemotherapy regimens.<\/jats:p>","DOI":"10.1111\/j.1600-0609.2006.00708.x","type":"journal-article","created":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T15:13:05Z","timestamp":1153408385000},"page":"293-299","source":"Crossref","is-referenced-by-count":19,"title":["Efficacy of liposomal daunorubicin and cytarabine as reinduction chemotherapy in relapsed acute lymphoblastic leukaemia despite expression of multidrug resistance\u2010related proteins"],"prefix":"10.1111","volume":"77","author":[{"given":"Anna","family":"Candoni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Michelutti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Simeone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Damiani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Baccarani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renato","family":"Fanin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,19]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11664"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2002.1.162"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19991001)86:7<1216::AID-CNCR17>3.0.CO;2-O"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-03-0704"},{"key":"e_1_2_5_6_2","first-page":"3135","article-title":"Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings and outcome. 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