title: Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival.
abstract: OBJECTIVE
  To test whether eradication of minimal residual disease (MRD) in B-cell chronic lymphocytic leukemia (CLL) by alemtuzumab is associated with a prolongation of treatment-free and overall survival.
  
  
  METHODS
  Ninety-one previously treated patients with CLL (74 men and 17 women; median age, 58 years [range, 32 to 75 years]; 44 were refractory to purine analogs) received a median of 9 weeks of alemtuzumab treatment between 1996 and 2003. Regular bone marrow assessments by MRD flow cytometry were performed with the aim of eradicating detectable MRD (< 1 CLL cell in 10(5) normal cells).
  
  
  RESULTS
  Responses according to National Cancer Institute-sponsored working group response criteria were complete remission (CR) in 32 patients (36%), partial remission (PR) in 17 patients (19%), and no response (NR) in 42 patients (46%). Twenty-two (50%) of 44 purine analog-refractory patients responded to alemtuzumab. Detectable CLL was eradicated from the blood and marrow in 18 patients (20%). Median survival was significantly longer in MRD-negative patients compared with those achieving an MRD-positive CR, PR, or NR. Patients achieving an MRD-negative CR had a longer treatment-free survival than patients with MRD-positive CRs, PR, or NR: MRD-negative CRs, not reached; MRD-positive CRs, 20 months; PRs, 13 months; NR, 6 months (P < .0001). Overall survival for the 18 patients with MRD-negative remissions was 84% at 60 months. Eight (47%) of the MRD-negative patients converted to MRD positivity at a median of 28 months.
  
  
  CONCLUSIONS
  MRD-negative remission in CLL is achievable with alemtuzumab, leading to an improved overall and treatment-free survival.
authors.affiliation: Leeds Teaching Hospitals, NHS Trust, Great George St, Leeds, LS1 3EX United Kingdom. paul-moreton@ntlworld.com
authors.forename: Paul
authors.initials: P
authors.lastname: Moreton
authors.forename: Ben
authors.initials: B
authors.lastname: Kennedy
authors.forename: Guy
authors.initials: G
authors.lastname: Lucas
authors.forename: Michael
authors.initials: M
authors.lastname: Leach
authors.forename: Saad M B
authors.initials: SM
authors.lastname: Rassam
authors.forename: Andrew
authors.initials: A
authors.lastname: Haynes
authors.forename: Jane
authors.initials: J
authors.lastname: Tighe
authors.forename: David
authors.initials: D
authors.lastname: Oscier
authors.forename: Christopher
authors.initials: C
authors.lastname: Fegan
authors.forename: Andy
authors.initials: A
authors.lastname: Rawstron
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab