title: Early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab.
abstract: BACKGROUND
  Patients with chronic lymphocytic leukemia (CLL) usually are treated only for progressive disease. However, the discovery of biologic predictors of a high risk of disease progression, together with the development of newer, more targeted therapies, could change this paradigm. In this phase 2 study, the authors tested the safety and efficacy of early treatment for patients with high-risk CLL using alemtuzumab and rituximab.
  
  
  METHODS
  Patients were eligible for treatment if they were 1) previously untreated, 2) had no National Cancer Institute-Working Group 1996 criteria for treatment, and 3) had at least 1 marker of high-risk disease 17p13-, 11q22-, or a combination of unmutated IgVH and CD38+/ZAP70+). Treatment consisted of subcutaneous alemtuzumab (initial dose escalation followed by 30 mg on Monday, Wednesday, and Friday for 4 weeks) and intravenous rituximab (375 mg/m(2) per week x4 doses). All patients received Pneumocystis pneumonia and herpes virus prophylaxis and were monitored for cytomegalovirus reactivation.
  
  
  RESULTS
  Twenty-seven of 30 patients (90%) responded to therapy with 11 (37%) complete responses (CRs). Five patients (17%) patients who had a CR had no detectable minimal residual disease. The median response duration was 14.4 months, and only 9 patients required retreatment for progressive disease at the time of the current report (median follow-up, 17.6 months). Study patients had a significantly longer time from diagnosis to first treatment for CLL according to conventional indications than a comparison cohort with similar biologic risk profiles.
  
  
  CONCLUSIONS
  The therapy regimen used was safe and effective for early treatment of patients with high-risk CLL. Further studies will be required to determine whether this early treatment strategy decreases morbidity and mortality for high-risk CLL.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota 55905, USA. zent.clive@mayo.edu
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
authors.forename: Renee C
authors.initials: RC
authors.lastname: Tschumper
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Bowen
authors.forename: Charla R
authors.initials: CR
authors.lastname: Secreto
authors.forename: Betsy R
authors.initials: BR
authors.lastname: Laplant
authors.forename: Brian F
authors.initials: BF
authors.lastname: Kabat
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay