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Related Experiment Video

Updated: Oct 23, 2025

From a 2DE-Gel Spot to Protein Function: Lesson Learned From HS1 in Chronic Lymphocytic Leukemia
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Lymphocyte Doubling Time As A Key Prognostic Factor To Predict Time To First Treatment In Early-Stage Chronic

Fortunato Morabito1,2, Giovanni Tripepi3, Riccardo Moia4

  • 1Department of Onco-Hematology Azienda Ospedaliera (AO) Cosenza, Biotechnology Research Unit, Cosenza, Italy.

Frontiers in Oncology
|August 19, 2021
PubMed
Summary

Lymphocyte doubling time (LDT) predicts treatment needs in chronic lymphocytic leukemia (CLL). A shorter LDT indicates a faster disease progression, aiding in personalized follow-up plans for early-stage CLL patients.

Keywords:
CLLTTFTearly stagelymphocyte doubling timeprognosis

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Area of Science:

  • Hematology
  • Oncology
  • Clinical Prognostics

Background:

  • Lymphocyte doubling time (LDT) has been a recognized prognostic factor in chronic lymphocytic leukemia (CLL) for over 30 years.
  • LDT measures the time for peripheral blood lymphocyte counts to double from an initial value.
  • The prognostic significance of LDT in relation to time to first treatment (TTFT) requires contemporary validation.

Purpose of the Study:

  • To explore and validate the prognostic value of LDT for TTFT in newly diagnosed Binet stage A CLL patients.
  • To assess the added value of LDT when combined with other established prognostic markers.
  • To refine follow-up strategies for early-stage CLL patients using LDT.

Main Methods:

  • Prospective enrollment of newly diagnosed Binet stage A CLL patients into the O-CLL1-GISL protocol (Italy).
  • Validation using two independent cohorts of newly diagnosed CLL patients from Novara (Italy) and Barcelona (Spain).
  • Cox multivariate regression analysis incorporating LDT, IGHV mutational status, genetic markers (11q, 17p deletions), beta2-microglobulin, Rai stage, and NOTCH1 mutations.

Main Results:

  • A shorter LDT (≤ 12 months) was significantly associated with a shorter TTFT in the training cohort.
  • LDT ≤ 12 months independently predicted shorter TTFT alongside IGHV unmutated status, 11q/17p deletions, elevated β2M, Rai stage I-II, and NOTCH1 mutations.
  • Regression models incorporating LDT demonstrated significantly better data fitting and prognostic accuracy compared to models without LDT.

Conclusions:

  • Lymphocyte doubling time (LDT) remains a valuable prognostic factor for predicting time to first treatment in early-stage CLL.
  • LDT can be effectively integrated with other sophisticated prognostic markers to enhance risk prediction and personalize patient management.
  • Utilizing LDT can aid in optimizing follow-up schedules for Binet stage A CLL patients.