The prognostic significance of lymphocyte doubling time (LDT) in chronic lymphocytic leukemia (CLL) was identified when the biology of the disease was poorly understood and therapy was not effective. We assessed the clinical and biological significance of LDT in 848 CLL patients in a real-life setting and the context of new biomarkers and effective therapy. A short LDT (≤12 months) was enriched for adverse biomarkers. Patients with a rapid LDT did need therapy shortly after diagnosis (median 23 months vs. not reached; p < 0.001) and had a poorer overall survival (median 95 months vs. not reached p < 0.001). LDT, IGHV mutational status, Beta-2 microglobulin, and Rai clinical stage were independent predictors for time to first treatment in the whole series and in Binet stage A patients. No correlation was observed between LDT and response to chemoimmunotherapy. However, a short LDT along with age ≥65 years, high-risk FISH (del(17p), del(11q)), unmutated IGHV, increased Beta-2 microglobulin, and TP53 mutations predicted short survival. Moreover, the prognostic significance of LDT was independent of the CLL-IPI and the Barcelona/Brno prognostic model. LDT remains an important outcome marker in the modern CLL era and should be incorporated into the clinical assessment and stratification of CLL patients.
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This study was supported by Janssen research grant; Swiss Cancer League, ID 3746, 4395 4660, and 4705, Bern, Switzerland; European Research Council (ERC) Consolidator Grant CLLCLONE, ID: 772051; Swiss National Science Foundation, ID 320030_169670/1 and 310030_192439, Berne, Switzerland; The Leukemia & Lymphoma Society, Translational Research Program, ID 6594-20, New York. AIRC 5 × 1000 No. 21198, Associazione Italiana per la Ricerca sul Cancro Foundation Milan, Italy; the AGING Project—Department of Excellence—DIMET, Università del Piemonte Orientale, Novara, Italy; Ricerca Finalizzata 2018 (project RF-2018-12365790), MoH, Rome, Italy.
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Baumann, T., Moia, R., Gaidano, G. et al. Lymphocyte doubling time in chronic lymphocytic leukemia modern era: a real-life study in 848 unselected patients. Leukemia 35, 2325–2331 (2021). https://doi.org/10.1038/s41375-021-01149-w