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.
- SourceAvailable from: Jeremy L Warner
[Show abstract] [Hide abstract]
- "Subsequent to the initial seminal phase II trials, we identified 12 further published trials examining the efficacy of single-agent intravenous alemtuzumab in the relapsed setting [Ferrajoli et al. 2003; Lozanski et al. 2004; Rawstron et al. 2004; Rieger et al. 2004; Thieblemont et al. 2004; Laurenti et al. 2005; Lin et al. 2005; Moreton et al. 2005; Majolino et al. 2006; Ionita et al. 2009; Kataeva et al. 2009; Zagoskina et al. 2011]. Five of these trials had at least 20 patients enrolled (Table 1). "
ABSTRACT: In this review, we outline the clinical experience with single-agent alemtuzumab as a treatment for relapsed and refractory chronic lymphocytic leukemia (CLL) in both prospective and retrospective trials and describe the multiagent use of the drug with the goal of updating clinicians on recent developments and possible future rational combinations. Alemtuzumab, an antibody targeting the lymphocyte-specific surface marker CD52, is an approved agent for the treatment of CLL. Despite its demonstrated efficacy, likely secondary to concerns regarding infectious complications, it is most commonly used in the relapsed and refractory setting. Given alemtuzumab's unique mechanism of action it has been demonstrated to have activity in disease that is refractory to both alkylating agents and purine analogs. Furthermore, it has activity in TP53-mutated disease, which has the worst prognosis of any subset of CLL. Alemtuzumab has greater efficacy on circulating disease relative to nodal disease. Rational combinations are attempting to use these attributes to increase response rates in patients with relapsed and refractory disease.12/2012; 3(6):375-89. DOI:10.1177/2040620712458949
- [Show abstract] [Hide abstract]
ABSTRACT: Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2009; 24(3):652-4. DOI:10.1038/leu.2009.240 · 9.38 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The choice of salvage therapy for patients presenting relapsed chronic lymphocytic leukemia (CLL) has to take into account some factors influencing tumor resistance and comorbidities. Since 2010, new drugs targeting the tumor cells' signaling have been proposed for CLL patients. Waiting the results of various clinical trials evaluating these treatments, there is a need to describe the state-of-the-art concerning approved treatments such as chemotherapy and monoclonal antibodies.Bulletin du cancer 12/2012; 99(12). DOI:10.1684/bdc.2012.1673 · 0.64 Impact Factor