Originally published as JCO Early Release 10.1200/JCO.2005.04.6037 on April 17 2006

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Alemtuzumab As Consolidation After a Response to Fludarabine Is Effective in Purging Residual Disease in Patients With Chronic Lymphocytic Leukemia

Marco Montillo, Alessandra Tedeschi, Sara Miqueleiz, Silvio Veronese, Roberto Cairoli, Liliana Intropido, Francesca Ricci, Anna Colosimo, Barbara Scarpati, Michela Montagna, Michele Nichelatti, Mario Regazzi, Enrica Morra

From the Department of Hematology, Department of Pathology, Laboratory of Flow Cytometry, Transfusion Medicine Service, Niguarda Ca'Granda Hospital, Milano; and the Department of Pharmacology IRCCS, Istituto di Ricovero e Cura a Carattere Scientifico-Policlinico S. Matteo, Pavia, Italy

Address reprint requests to Marco Montillo, MD, Dipartimento di On cologia Ematologia, Divisione di Ematologia, Ospedale Niguarda Ca'Granda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy; e-mail: marco.montillo{at}ospedaleniguarda.it

Purpose 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.

Patients and 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.

Conclusion 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' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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