title: High-risk fludarabine-pretreated B-cell chronic lymphocytic leukemia's high response rate following sequential DHAP and alemtuzumab administration though in absence of molecular remission.
abstract: B-CLL patients with resistant/relapsed disease or adverse prognostic factors at presentation are suitable for alternative treatments. In the present pilot study we investigated a novel intensive chemo-immunotherapy approach for high-risk, fludarabine pretreated patients. Ten patients with resistant/relapsed, advanced stage BCLL were included. Age was 37-60 yr (median 53). All but one had an unmutated IgVH status. The treatment schedule included debulking with two DHAP courses followed by alemtuzumab (30 mg, eight doses), followed by peripheral blood progenitor cell (PBPC) mobilization with intermediate/high-dose cyclophosphamide and by autografting after high-dose mitoxantrone+L-Pam. The DHAP-alemtuzumab combination was highly effective. Eight patients out of 10 responded to DHAP, with a single complete remission. Following alemtuzumab, the number of overall responses increased to nine, and the complete remissions to five. After alemtuzumab PB double-positive clonal CD5+/CD19+ lymphocytes dropped, with median purification rate 99.95%. Owing to poor PBPC mobilization, only five patients underwent autografting, and three of these experienced post-graft recurrence. The six patients entering complete remission were free of disease 3-23 mo after study entry, and three of them were still in remission at 3, 7, and 22 mo. However, molecular evaluation regularly revealed persistence of minimal residual disease, both in all PBPC collections tested and in post-treatment follow-up samples. The use of DHAP/alemtuzumab appears useful to re-induce disease remission in relapsed/refractory, high-risk B-CLL patients. However, the addition of autograft was not usually feasible and of questionable clinical use. Other strategies should thus be considered for remission maintenance.
authors.affiliation: UO Ematologia e TMO, Azienda Ospedaliera S. Camillo-Forlanini, Roma, Italy. imajolino@scamilloforlanini.rm.it
authors.forename: Ignazio
authors.initials: I
authors.lastname: Majolino
authors.forename: Marco
authors.initials: M
authors.lastname: Ladetto
authors.forename: Anna
authors.initials: A
authors.lastname: Locasciulli
authors.forename: Daniela
authors.initials: D
authors.lastname: Drandi
authors.forename: Fabio
authors.initials: F
authors.lastname: Benedetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallamini
authors.forename: Teodoro
authors.initials: T
authors.lastname: Chisesi
authors.forename: Angelo
authors.initials: A
authors.lastname: De Blasio
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence; D012074:Remission Induction; D013234:Stem Cells / Q000166:cytology*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D003561:Cytarabine; D000074323:Alemtuzumab; D003907:Dexamethasone; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D002945:Cisplatin