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Predicting Which Patients with Chronic Lymphocytic Leukemia Might Need Early Treatment

A new laboratory-based scoring system may allow physicians to better predict which patients with early-stage CLL are most likely to require early treatment.
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Knowing which patients are most likely to benefit from treatment is a crucial part of medicine. That is especially true for patients with chronic lymphocytic leukemia (CLL), a hematologic cancer that can often go years or even decades without progressing to a state that requires medical treatment.1

Clinical staging allows physicians to predict how a cancer might progress, and identify which patients might need immediate treatment. For patients with CLL, the most commonly used staging systems include the Rai (which stages from a low of stage 0 to a high of stage IV) and the Binet (which stages from a low of stage A to a high of stage C) classifications. Both the 40-year-old Rai and Binet systems provide physicians with a simple and inexpensive way to assess a patient’s CLL.2 However, because patients today are generally diagnosed at earlier stages of disease than those in the past, the predictive powers of the Rai and Binet systems are proving to be more and more limited.2

In a recent study, investigators sought to improve the current CLL staging systems by integrating traditional clinical factors, such as age, gender, and white blood cell count, with modern molecular biomarkers that include genetic and chemical signatures associated with CLL.2 More specifically, the researchers wanted to identify those characteristics that would allow them to predict how long patients with Rai stage 0 CLL were likely to remain treatment-free.2

After evaluating 1201 cases of CLL in a single center, including 478 cases that were Rai stage 0, the investigators confirmed that patients with Rai stage 0 CLL were much more likely to have a long treatment-free period compared with those with Rai stage I-IV cancers.2 In fact, patients with early-stage Rai 0 cancers generally went about twice as long without treatment as those with later stage cancers (10 years vs 5 years).2 Looking more closely at the characteristics of the patients and their cancers, 5 variables were found to be likely predictors of a patient having a short treatment-free period:

  • White blood cell count >32,000 cells/µL
  • Deletion in the small arm of chromosome 17 (medically known as del17p)
  • Deletion in the long arm of chromosome 11 (del11q)
  • Extra copy of chromosome 12 (trisomy 12)
  • Unmutated copy of the gene IGHV2

Using these parameters, the investigators developed a scoring system that they termed the CRO score.2 To confirm that the CRO score worked in identifying patients with early-stage CLL who were likely to have a short treatment-free period, the investigators applied the scoring to real-world patient populations from 4 other hospitals around the world.2 In each case, and despite substantial differences among the types of patients in these populations, CRO scoring allowed the researchers to predict which patients were likely to require earlier treatment.2 Additionally, the researchers were able to show that the predictive power of CRO scoring could extend to patients with Rai stage I CLL.2

Results of this study suggest that CRO scoring could be a valuable new tool to aid clinical decision-making in cases of early-stage CLL. Further research is needed to definitively validate its use in this setting.


  1. Davis LE. Watchful Waiting Approaches for CLL Patients. Patient Power. Published July 21, 2020. Accessed March 1, 2021.
  2. Cohen JA, Rossi FM, Zucchetto A, et al. A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia. Haematologica. 2020;105:1613-1620.

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Last modified: April 19, 2021

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