The prevalence, clinical characteristics, and prognostic significance of immune thrombocytopenia (IT) in patients with chronic lymphocytic leukemia (CLL) have not been clearly determined. To clarify this, we retrospectively analyzed 1278 consecutive newly diagnosed patients with CLL. Criteria for IT diagnosis included the following: rapid (< 2 weeks) and severe fall (half of the initial level and below 100 ؋ 10 9 /L) in platelet count; normal or augmented megakaryocytes in bone marrow; no or limited (not palpable) splenomegaly; no cytotoxic treatment in the preceding month. Sixty-four patients (5%) were diagnosed with IT. The median time to IT from CLL diagnosis was 13 months (range, 0-81 months), and median platelet count at IT diagnosis was 14 ؋ 10 9 /L (range, 1-71 ؋ 10 9 /L). Fifty-six of the 64 patients (87%) received treatment for IT. The probability of responding to treatment for IT was significantly higher for patients receiving chemotherapy with or without steroids than for patients treated with intravenous immunoglobulins with or without steroids (P ‫؍‬ .01). The development of IT was significantly associated with unmutated IgVh, a positive direct antiglobulin test, and the occurrence of autoimmune hemolytic anemia. Patients with CLL and IT had poorer survival than other patients with CLL (5-year overall survival 64% vs 82%, P < .001), and this effect was independent from common clinical prognostic variables.

The online version of this article has a Supplementary Appendix. BackgroundB-cell chronic lymphocytic leukemia is a clinically heterogeneous disease; some patients rapidly progress and die within a few years of diagnosis, whereas others have a long life expectancy with minimal or no treatment. Telomere length and telomerase levels have been proposed as prognostic factors; however, very few cases have been characterized for both parameters and no study has analyzed the prognostic value of the telomere/telomerase profile. Design and MethodsOne hundred and seventy-three cases of chronic lymphocytic leukemia were characterized for telomere lengths and telomerase levels by real-time polymerase chain reaction. Data were correlated with established prognostic markers, IGVH mutational status and chromosomal aberrations, and clinical outcome. ResultsTelomere lengths were inversely correlated with telomerase levels (rs= -0.213; P=0.012), and most of the cases of chronic lymphocytic leukemia with high levels (above median) of telomerase had short (below median) telomeres (P=0.0001). Telomerase levels were higher and telomeres were shorter in unmutated IGVH cases than in mutated IGVH ones (P<0.0001). Chronic lymphocytic leukemias with 11q, 17p deletion or 12 trisomy had significantly higher levels of telomerase and shorter telomeres than those with no chromosomal aberration or the sole 13q deletion (P<0.001). Telomere length/telomerase level profiles identified subgroups of patients with different clinical outcomes (P<0.0001), even within the subsets of chronic lymphocytic leukemia defined by IGVH mutational status or chromosomal aberrations. Short telomere/high telomerase profile was independently associated with more rapid disease progression. ConclusionsComprehensive analyses of telomeres, telomerase, chromosomal aberrations, and IGVH mutational status delineate groups of chronic lymphocytic leukemias with distinct biological characteristics and clinical outcomes. The telomere/telomerase profile may be particularly useful in refining the prognosis of chronic lymphocytic leukemia patients with mutated IGVH and no high-risk chromosomal aberrations.Key words: B-CLL, telomere, telomerase, chromosomal aberrations. Bonaldi L, Trentin L, Visco C, Keppel S, Giunco S, Frezzato F, Facco M, Novella E, Giaretta I, Del Bianco P, Semenzato G, and De Rossi A. Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes. Haematologica 2012;97(1):56-63. doi:10.3324/haematol.2011 Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes

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ABSTRACTexpressed in early stages of CLL than in advanced CLL 17 and that its expression is lower in patients with high-risk CLL. 16