title: Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia.
abstract: Alemtuzumab therapy is effective for some refractory chronic lymphocytic leukemia (CLL), but identifying responders requires at least 8 weeks of therapy. Early identification of nonresponders would minimize toxicity and/or facilitate more effective strategies. The aim of this study was to identify a minimally invasive method for early prediction of response and relapse. Flow cytometric monitoring was performed in 887 blood samples and 201 marrow samples from 43 patients undergoing intravenous alemtuzumab therapy. Although the absolute lymphocytosis was resolved in all patients by week 4, significant depletion of bone marrow tumor only occurred if circulating B-lymphocyte counts were persistently less than 0.001 x 10(9)/L, which was rare in nonresponders. The majority of patients (16/28) who did not benefit from a full course of therapy were identified with 100% positive predictive value using the following algorithm: peripheral B-cell count greater than 0.001 x 10(9)/L at week 2 with less than 1 log depletion of circulating B cells between weeks 2 and 4. Monitoring CLL levels after treatment identified patients at risk of early disease progression and could potentially improve patient management. During alemtuzumab therapy, bone marrow CLL depletion only occurs after abrogation of circulating tumor, requiring close monitoring of circulating B-cell levels. If validated in prospective studies, blood monitoring at 2 and 4 weeks may be used to optimize therapy.
authors: Academic Unit of Haematology and Oncology, Haematological Malignancy Diagnostic Service, Leeds General Infirmary, United Kingdom. andy.rawstone@hmds.org.uk
authors: Andy C
authors: AC
authors: Rawstron
authors: Ben
authors: B
authors: Kennedy
authors: Paul
authors: P
authors: Moreton
authors: Anita J
authors: AJ
authors: Dickinson
authors: Matthew J
authors: MJ
authors: Cullen
authors: Stephen J
authors: SJ
authors: Richards
authors: Andrew S
authors: AS
authors: Jack
authors: Peter
authors: P
authors: Hillmen
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000166:cytology; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000473:pathology; D011237:Predictive Value of Tests; D012008:Recurrence; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab