title: Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine.
abstract: OBJECTIVE
  This phase II pilot study determined the efficacy and safety of alemtuzumab (Campath-1H; Burroughs Wellcome, United Kingdom) in patients with chronic lymphocytic leukemia (CLL), all of whom had previously received fludarabine and other chemotherapy regimens.
  
  
  METHODS
  Twenty-four patients were treated with intravenous alemtuzumab at six centers in the United States. The target dose of 30 mg over 2 hours, three times weekly, was administered for up to 16 weeks. Responses were evaluated by an independent panel of experts using 1996 National Cancer Institute-sponsored Working Group criteria. Safety assessments included analysis of lymphocyte subpopulations. Antimicrobial prophylaxis was not mandatory.
  
  
  RESULTS
  Eight patients (33%) achieved a major response (all partial remissions), with a median time to response of 3.9 months (range, 1.6 to 5.3 months). The median duration of response was 15.4 months (range, 4.6 to >or= 38.0 months), the median time to disease progression was 19.6 months (range, 7.7 to >or= 42.0 months), and the median survival time was 35.8 months (range, 8.8 to >or= 47.1 months). Acute infusion-related events, mainly grades 1 and 2, were most common and most severe in the first week. Ten patients (eight nonresponders and two responders) experienced major infections on-study. Pneumocystis carinii pneumonia was reported in two patients on-study; neither had received prophylaxis. Median CD4+ and CD8+ counts decreased and then began to increase by the end of the study, with further recovery by 1-month follow-up. One of 53 samples obtained from 10 patients had a low titer of alemtuzumab antibodies.
  
  
  CONCLUSIONS
  Alemtuzumab has significant activity in poor-prognosis, fludarabine-treated CLL patients. However, because of a relatively high incidence of opportunistic infections accompanying profound lymphopenia, future protocols should include mandatory prophylaxis.
authors.affiliation: Long Island Jewish Medical Center, New Hyde Park, NY 11040, USA. rai@lij.edu
authors.forename: K R
authors.initials: KR
authors.lastname: Rai
authors.forename: C E
authors.initials: CE
authors.lastname: Freter
authors.forename: R J
authors.initials: RJ
authors.lastname: Mercier
authors.forename: M R
authors.initials: MR
authors.lastname: Cooper
authors.forename: B S
authors.initials: BS
authors.lastname: Mitchell
authors.forename: E A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: P
authors.initials: P
authors.lastname: Santábarbara
authors.forename: B
authors.initials: B
authors.lastname: Wacker
authors.forename: L
authors.initials: L
authors.lastname: Brettman
mesh_terms: D000293:Adolescent; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D015461:Leukemia, Prolymphocytic, T-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D009894:Opportunistic Infections; D010865:Pilot Projects; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D017211:Treatment Failure; D016896:Treatment Outcome; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000074323:Alemtuzumab; D004248:DNA (Cytosine-5-)-Methyltransferases; D014740:Vidarabine; C024352:fludarabine