title: Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemia.
abstract: BACKGROUND
  The objective of this study was to investigate the efficacy and safety of alemtuzumab, the humanized anti-CD52 monoclonal antibody, in patients with B-cell chronic lymphocytic leukemia and residual disease after chemotherapy.
  
  
  METHODS
  Forty-one patients received alemtuzumab 3 times weekly for 4 weeks. The first 24 patients received 10 mg per dose, and the next 17 patients received 30 mg. All patients received infection prophylaxis during therapy and for 2 months after treatment.
  
  
  RESULTS
  The overall response rate was 46%, including 39% of patients who received the 10 mg dose and responded versus 56% of the patients who received the 30 mg dose. The major reason for failure to respond was the presence of adenopathy. Residual bone marrow disease cleared in most patients, and 11 of 29 patients (38%) achieved a molecular disease remission. The median time to disease progression had not been reached in responders with a median follow-up of 18 months. Six patients remained in disease remission between 24-38 months after therapy. Infusion-related events were common with the initial doses, but all such events were NCI Common Toxicity Criteria Grade 1-2. Infections were reported to occur in 15 patients (37%), and 9 of these infections were reactivation of cytomegalovirus. Three patients developed Epstein-Barr virus positive, large cell lymphoma. Two patients had spontaneous resolution of the lymphoma and, in one patient, the lymphoma resolved after treatment with cidofovir and immunoglobulin.
  
  
  CONCLUSIONS
  Alemtuzumab produced significant responses in patients with residual disease after chemotherapy. Bone marrow disease was eradicated more frequently than lymph node disease, and molecular disease remissions were achieved. A randomized trial comparing alemtuzumab with observation after chemotherapy is indicated.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. sobrien@mdanderson.org
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Thomas
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
authors.forename: Charles A
authors.initials: CA
authors.lastname: Koller
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Mary
authors.initials: M
authors.lastname: Browning
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000074301:CD52 Antigen; D020031:Epstein-Barr Virus Infections / Q000821:virology; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000821:virology; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000821:virology; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab