title: Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia.
abstract: Little information is available on long-term immune reconstitution after therapy with alemtuzumab in B-CLL patients. We present long-term follow-up data for blood lymphocyte subsets analysed by flow cytometry in previously untreated B-CLL patients who received alemtuzumab subcutaneously as first-line therapy. All lymphoid subsets were significantly (P<0.001) and profoundly reduced; the median end-of-treatment counts for CD4(+), CD8(+), CD3(-)56(+) (natural killer (NK)), CD3(+)56(+) (NK-T) and CD19(+)5(-) (normal B) cells were 43, 20, 4, 1 and 8 cells/microl, respectively. The median cell count of all subsets remained at <25% of the baseline values for >9 months post-treatment. CD4(+) and CD8(+) levels in blood had reached >100 cells/microl in >50% of the patients at 4 months after the end of treatment. One patient had a cytomegalovirus reactivation and one patient developed Pneumocystis carinii pneumonia during therapy. No opportunistic or other major infections were recorded during unmaintained, long-term follow-up. There was no correlation between the cumulative dose of alemtuzumab and the severity or length of immunosuppression. CD52(-) T-cell subsets occurred during the treatment and comprised >80% of all CD4(+) and CD8(+) cells in the blood at the end of therapy. These subpopulations declined gradually during unmaintained follow-up. The relationship between these observations and the safety/antitumour effects of alemtuzumab is discussed.
authors.affiliation: 1Department of Haematology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Lundin
authors.forename: A
authors.initials: A
authors.lastname: Porwit-MacDonald
authors.forename: E D
authors.initials: ED
authors.lastname: Rossmann
authors.forename: C
authors.initials: C
authors.lastname: Karlsson
authors.forename: P
authors.initials: P
authors.lastname: Edman
authors.forename: M R
authors.initials: MR
authors.lastname: Rezvany
authors.forename: E
authors.initials: E
authors.lastname: Kimby
authors.forename: A
authors.initials: A
authors.lastname: Osterborg
authors.forename: H
authors.initials: H
authors.lastname: Mellstedt
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D015703:Antigens, CD / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016022:Case-Control Studies; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D007694:Killer Cells, Natural / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology*; D008875:Middle Aged; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000970:Antineoplastic Agents; D000074323:Alemtuzumab