RESUMO
This prospective, single-arm study utilized alemtuzumab as a single agent in a novel maintenance schedule in previously treated chronic lymphocytic leukemia patients with the goal of delaying progression of disease and requirement for chemotherapy. In previously treated CLL patients who had achieved stable disease or better, the following schedule of subcutaneous alemtuzumab was administered: a dose escalation in the first week (3, 10 and 30 mg), followed by 7 weeks of 30 mg alemtuzumab once weekly, 16 weeks of 30 mg once every 2 weeks, followed by once every 3 weeks for 24 weeks. Thus, the entire duration of the planned treatment was 48 weeks. A total of 12 patients were enrolled 11 of which had at least one marker of poor prognosis (unmutated, Zap 70+, CD38+, del11q and del17p). The median chemotherapy-free interval was 13 months, and the median time to disease progression was 10 months. Three patients achieved a CR, one achieved nPR, one had a PR, five failed and two had shown a beneficial response but because of recurrent ITP had to stop alemtuzumab. In six of the 10 patients with previously relapsed disease, the chemotherapy-free interval was longer than their prior chemotherapy-free period. One patient had a reactivation of CMV antigenemia, and another had a bacterial pneumonia. There were no grade 3 or 4 toxicities. Alemtuzumab used in a maintenance schedule is a potentially safe and useful tool in delaying disease progression and chemotherapy-free intervals in previously treated CLL patients.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/efeitos adversos , Antineoplásicos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Auto-immune hemolytic anemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) are known complications of chronic lymphocytic leukemia (CLL). Rituximab, cyclophosphamide and dexamethasone (RCD) effectively target lymphocytes and inhibit autoimmune processes. We reviewed 21 patients with CLL treated for AIHA alone (n = 18), ITP alone (n = 1) or both (n = 2) with the following RCD regimen: rituximab 375 mg/m(2) i.v. infusion given on day 1, cyclophosphamide 750-1000 mg/m(2) i.v. on day 2 and dexamethasone 12 mg day 1-7 given every 3 weeks. Response to treatment was seen in all 20 patients with CLL with AIHA. Median hemoglobin pre-treatment was 8 g/dL. The median change in hemoglobin was 5.2 g/dL and the median post-treatment hemoglobin level was noted to be 13.1 g/dL. Median duration of response was 22 months. Nine relapsed patients responded as well. Fifty percent of evaluable patients converted to Coombs negative with median duration of response of 41 months vs. 10 months for those who did not convert. This difference was not statistically significant (p = 0.0674). Steroid-refractory immune thrombocytopenia was present in three patients and all responded to RCD. There were no hospitalisations or infections directly related to RCD. RCD is a safe and effective regimen in the treatment of immune cytopenias associated with CLL.