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: 10.43). 10/2009; 115(2):187-97. DOI: 10.1182/blood-2009-08-207126
Source: PubMed

ABSTRACT 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, Jul 28, 2015
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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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    • "CLL is the most common leukemia in western countries, occurring predominantly in patients older than 65 years of age [1]. Still the case we report is rare, concerning an older patient compared to previous published clinical cases. "
    European geriatric medicine 11/2012; 3(6):374–375. DOI:10.1016/j.eurger.2012.08.005 · 0.55 Impact Factor
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    • "fludarabine , cyclophosphamide, rituximab) do not provoke an excess of AIHA, and patients with a previous history of non-fludarabine related AIHA or a positive DAT can be safely treated with such regimens (Borthakur et al, 2007; Dearden et al, 2008; Hallek et al, 2010). Indeed, the optimal therapy for the autoimmune cytopenia can be the best possible treatment for CLL (Gribben, 2010). However, in patients with active CLL and immune cytopenia, particularly AIHA, it makes sense to try to control the autoimmune process before giving antileukaemic therapy that will impair the function of a bone marrow whose function is already weakened by the disease infiltration and the autoimmune cytopenia (Zent & Shanafelt, 2009). "
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    ABSTRACT: Autoimmune cytopenia, especially autoimmune haemolytic anaemia (AIHA), appears in 5-10% of patients with chronic lymphocytic leukaemia (CLL). In these patients, the prognosis is not as poor as in those cases in which the cytopenia is due to a massive bone marrow infiltration by the disease, and their treatment requires special considerations. For these reasons, the diagnosis of autoimmune cytopenia should be entertained in any patient with CLL presenting with cytopenia. In patients with autoimmune cytopenia and CLL, treatment is as for idiopathic autoimmune cytopenia, with most patients responding to corticosteroids. For patients not responding to corticosteroids, splenectomy is a reasonable treatment choice. Monoclonal antibodies and thrombopoietin analogues have shown enough activity to support their use, especially within clinical studies, in selected cases not responding to corticosteroids and before splenectomy. In patients with resistant immune cytopenia, the most effective treatment is that of the underlying CLL. Fear of fludarabine-associated AIHA is no longer appropriate in the age of chemo-immunotherapy. Finally, prospective studies are required to better identify the optimal therapy for these patients.
    British Journal of Haematology 07/2011; 154(1):14-22. DOI:10.1111/j.1365-2141.2011.08707.x · 4.96 Impact Factor
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