How I treat CLL up front

Institute of Cancer, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, United Kingdom.
Blood (Impact Factor: 10.45). 10/2009; 115(2):187-97. DOI: 10.1182/blood-2009-08-207126
Source: PubMed


Although chronic lymphocytic leukemia (CLL) remains incurable, over the past decade there have been major advances in understanding the pathophysiology of CLL and in the treatment of this disease. This has led to greatly increased response rates and durations of response but not yet improved survival. Advances in the use of prognostic factors that identify patients at high risk for progression have led us to the question whether there is still a role for a "watch and wait" approach in asymptomatic high-risk patients or whether they should be treated earlier in their disease course. Questions remain, including, what is the optimal first-line treatment and its timing and is there any role of maintenance therapy or stem cell transplantation in this disease? CLL is a disease of the elderly and not all patients are eligible for aggressive up-front chemoimmunotherapy regimens, so what is the optimal treatment approach for more frail elderly patients? It is highly likely that our treatment approaches will continue to evolve as the results of ongoing clinical trials are released and that further improvements in the outcome of this disease will result from identification of therapies that target the underlying pathophysiology of CLL.

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Available from: John G Gribben,
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    • "Discussion CLL is predominantly a disease of older people , with a median age at diagnosis of 72 years [ Gribben , 2010 ] . Given the advanced age of affected individuals , management must often be tailored to accommodate specific patient character - istics , such as physical fitness , comorbidities , and degree of tolerability for treatment [ Hallek , 2009 ] . "
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    ABSTRACT: Bendamustine is a unique cytotoxic agent active against various human malignancies, including chronic lymphocytic leukemia (CLL). In vitro studies suggest that cytotoxic activity of bendamustine on CLL-derived cells is synergized by rituximab. A retrospective chart review was conducted to characterize treatment-naïve outpatients and those with relapsed disease aged 70 years and over with CLL receiving bendamustine (with or without rituximab) and to evaluate real-world patterns of care, safety, and effectiveness. Using McKesson Specialty Care/US Oncology Network iKnowMed databases, 91 outpatients with at least two recorded visits and at least two cycles of bendamustine monotherapy or bendamustine-rituximab combination therapy were identified and included. Mean age at diagnosis and start of first therapy was 70.3 and 77.4 years respectively, and 63.7% of patients were men. Observed overall response rate was 56.3% in pooled treatment-naïve patients [n = 9; complete response (CR) 18.8%; partial response (PR) 37.5%; nodular partial response (nPR) 0%] and 58.7% in pooled patients with relapsed disease (n = 44; CR 13.3%; PR 44.0%; nPR 1.3%). Median time to progressive disease has not been reached for the 16 treatment-naïve patients (median follow up 15.1 months), and was 18.4 months for those with relapsed disease (n = 73). No unexpected toxicities were observed. Overall rate of blood/bone marrow toxicities (all grades) was 40.7%; grade 3/4 rates were 18.8% in treatment-naïve patients and 25.3% in those with relapsed disease. Most frequent nonhematologic adverse events were fatigue and rash. In this retrospective chart review of 91 outpatients with CLL aged 70 years and over, bendamustine (with or without rituximab) was an effective therapeutic option with manageable toxicity.
    06/2013; 4(3):157-71. DOI:10.1177/2040620713478629
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    • "Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries [1, 2], with very heterogeneous clinical course of CLL from indolent to aggressive [3]. Prognostic factors used currently in practice, such as mutational status of immunoglobulin heavy chain coding genes (IgVH), and expression of CD38 or ZAP70 (zeta-associated protein), have shown their significance in CLL, but are time-consuming and require standardization of laboratory protocol [4, 5]. "
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    ABSTRACT: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Western countries. It is characterized by heterogeneous clinical course of the disease and new prognostic factors are still needed. CD74 plays an important role in signal transduction in B cell proliferation and survival pathway. CD74 expression has been shown in solid tumors and has been connected with poor prognosis and tumor progression. The aim of the study was to evaluate the expression of CD74 in chronic lymphocytic leukemia patients with combination with other known prognostic factors. Expression of CD74 was determined in 90 patients and 28 healthy controls. CD74 expression was significantly higher in CLL group than in controls. There was positive correlation between CD74 and ZAP70 expression (p = 0.008). High expression of CD74 was positively correlated with more advanced stage of the disease (p = 0.02). No correlation was shown between CD74 and sex, mutational status IgVH and time to first treatment.
    Medical Oncology 06/2013; 30(2):560. DOI:10.1007/s12032-013-0560-5 · 2.63 Impact Factor
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    • "The choice of treatment for autoimmune cytopenias in patients with CLL depends on whether the underlying disease also requires treatment.32 Patients with not-progressive CLL and autoimmune cytopenia not requiring treatment for the malignant disease are usually managed in the same manner as patients with a primary autoimmune cytopenia. "
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    ABSTRACT: Autoimmune cytopenias are a frequent complication in CLL, occurring in approximately 5–10% of the patients. The most common manifestation is autoimmune haemolytic anaemia, followed by immune thrombocytopenia and only rarely pure red blood cell aplasia or autoimmune granulocytopenia. Initial treatment is as for the idiopathic autoimmune cytopenias, with most patients responding to conventional corticosteroid therapy. Patients, who do not respond to conventional therapy after 4–6 weeks, should be considered for alternative immunosuppression, monoclonal antibody therapy or splenectomy. While randomized trials demonstrating the benefit of rituximab in CLL-related autoimmune diseases are still lacking, there are considerable data in the literature that provide evidence for its effectiveness. The monoclonal antibody alemtuzumab also displays considerable activity against both the malignant disease and the autoimmune complication in patients with CLL, although at the expense of greater toxicity. A number of new monoclonal antibodies, such as ofatumumab, GA-101, lumiliximab, TRU-016, epratuzumab, and galiximab, are currently investigated in CLL and their activity in CLL-related autoimmune cytopenias should be evaluated in future studies.
    Mediterranean Journal of Hematology and Infectious Diseases 04/2013; 5(1):e2013027. DOI:10.4084/MJHID.2013.027
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