title: Alemtuzumab as consolidation after a response to fludarabine is effective in purging residual disease in patients with chronic lymphocytic leukemia.
abstract: OBJECTIVE
  Treatment with alemtuzumab has resulted in negative responses for minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL). In a prior analysis we demonstrated that it is possible to achieved MRD negativity, as assessed by polyclonality of immunoglobulin heavy chain after consolidation with alemtuzumab. This phase II study evaluated 34 patients with CLL who received alemtuzumab consolidation in an effort to improve the quality of their response to fludarabine-based induction. Subsequent peripheral blood stem-cell (PBSC) collection and transplantation, tolerability, and pharmacokinetics also were assessed.
  
  
  METHODS
  Thirty-four patients younger than 65 years who had a clinical response to fludarabine-based induction therapy received alemtuzumab 10 mg subcutaneously three times per week for 6 weeks. PBSCs were collected after mobilization with cytarabine and granulocyte colony-stimulating factor. Blood samples for pharmacokinetics study were taken between days 1 and 31.
  
  
  RESULTS
  The complete response rate improved from 35% after fludarabine induction to 79.4% after alemtuzumab consolidation, including 19 patients (56%) who achieved MRD negativity. The most common adverse events were injection-site reactions and fever. Cytomegalovirus reactivation occurred in 18 patients, all of whom were successfully treated with oral ganciclovir. PBSC collection was successful in 24 (92%) of 26 patients, and 18 patients underwent autologous PBSC transplantation. Alemtuzumab plasma concentrations increased gradually during the first 2 weeks and accumulated more rapidly thereafter.
  
  
  CONCLUSIONS
  Subcutaneously administered alemtuzumab was effective, safe, and well tolerated as consolidation therapy in patients with CLL who responded to fludarabine induction therapy. Subsequent PBSCT was feasible thereafter.
authors.affiliation: Department of Hematology, Laboratory of Flow Cytometry, Transfusion Medicine Service, Niguarda Ca'Granda Hospital, Milano, Milan, Italy. marco.montillo@ospedaleniguarda.it
authors.forename: Marco
authors.initials: M
authors.lastname: Montillo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
authors.forename: Sara
authors.initials: S
authors.lastname: Miqueleiz
authors.forename: Silvio
authors.initials: S
authors.lastname: Veronese
authors.forename: Roberto
authors.initials: R
authors.lastname: Cairoli
authors.forename: Liliana
authors.initials: L
authors.lastname: Intropido
authors.forename: Francesca
authors.initials: F
authors.lastname: Ricci
authors.forename: Anna
authors.initials: A
authors.lastname: Colosimo
authors.forename: Barbara
authors.initials: B
authors.lastname: Scarpati
authors.forename: Michela
authors.initials: M
authors.lastname: Montagna
authors.forename: Michele
authors.initials: M
authors.lastname: Nichelatti
authors.forename: Mario
authors.initials: M
authors.lastname: Regazzi
authors.forename: Enrica
authors.initials: E
authors.lastname: Morra
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000627:therapeutic use*; D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000150:complications / Q000188:drug therapy; D005240:Feasibility Studies; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells; D006801:Humans; D007279:Injections, Subcutaneous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D015774:Ganciclovir