{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T13:03:39Z","timestamp":1769000619994,"version":"3.49.0"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,3,7]],"date-time":"2002-03-07T00:00:00Z","timestamp":1015459200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2002,3]]},"abstract":"<jats:p><jats:bold>Summary.<\/jats:bold> Chlorambucil has been used for many years for the treatment of low\u2010grade B\u2010cell lymphoproliferative disorders, including chronic lymphocytic leukaemia and low\u2010grade non\u2010Hodgkin's lymphoma. There is evidence in the literature that increasing the dose of chlorambucil produces better results than \u2018standard\u2019 doses in terms of response rates and overall survival. There is also evidence that this approach may be at least as effective as the use of fludarabine, as well as being very much less expensive. We describe a high\u2010dose chlorambucil (HDC) regimen, which involves a sustained but intermittent dose of chlorambucil, i.e. 30\u2003mg\/d for 4\u2003d per week for 4\u2003weeks, followed by a further four courses at fortnightly intervals for 8\u2003weeks (a total of eight 4\u2010d courses) given as a single drug over an initial 12\u2010week period. The outcome of treatment in previously treated and untreated patients was excellent, with a median time to treatment failure of 33\u2003months for the patient cohort overall and for previously treated and chemotherapy\u2010naive patients of 13 and 104\u2003months respectively. In patients previously treated with fludarabine, 78% had a response. Autoimmune haemolytic anaemia was reversed in one patient. Toxicity, both haematological and other, was minimal. We propose that escalated\u2010dose chlorambucil regimens should be compared with fludarabine in randomized controlled trials, rather than \u2018standard\u2019 lower dose protocols.<\/jats:p>","DOI":"10.1046\/j.0007-1048.2002.03362.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T06:43:05Z","timestamp":1047364985000},"page":"781-786","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["High\u2010dose chlorambucil for the treatment of chronic lymphocytic leukaemia and low\u2010grade non\u2010Hodgkin's lymphoma"],"prefix":"10.1111","volume":"116","author":[{"given":"Geoffrey P.","family":"Summerfield","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penelope R. A.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip J.","family":"Mounter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Proctor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,3,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"4990","DOI":"10.1182\/blood.V87.12.4990.bloodjournal87124990","article-title":"National Cancer Institute \u2013 Sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment","volume":"87","author":"Cheson B.D.","year":"1996","journal-title":"Blood"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1965.03080060018003"},{"key":"e_1_2_8_4_1","first-page":"843a","article-title":"High dose chemotherapy with autologous stem cell rescue for patients with CLL is an effective and safe means of inducing molecular responses: an MRC pilot study","volume":"96","author":"Forsyth P.D.","year":"2000","journal-title":"Blood"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1961.tb00321.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197303)31:3<502::AID-CNCR2820310303>3.0.CO;2-7"},{"key":"e_1_2_8_7_1","first-page":"437","article-title":"High dose chlorambucil vs intermittent chlorambucil plus prednisone for treatment of B\u2010CLL: IGCI CLL\u201001 trial","volume":"30","author":"Jaksic B.","year":"1988","journal-title":"Nouvelle Revue Francaise d'Hematologie"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19970601)79:11<2107::AID-CNCR7>3.0.CO;2-L"},{"key":"e_1_2_8_9_1","first-page":"758a","article-title":"Fludarabine vs. high dose chlorambucil in advanced B\u2010cell chronic lymphocytic leukaemia (B\u2010CLL): results of EORTC phase\u2010II randomised trial after 4 years of median follow\u2010up","volume":"96","author":"Jaksic B.","year":"2000","journal-title":"Blood"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197402)33:2<555::AID-CNCR2820330234>3.0.CO;2-I"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02897235"},{"key":"e_1_2_8_12_1","volume-title":"Chronic Lymphocytic Leukaemia Trial 4 (CLL4). 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