Chronic Lymphocytic Leukemia Coverage from Every Angle

Exposure to Chemotherapy and Risk of New Malignancies in Patients With CLL

By: Cordi Craig, MS
Posted: Wednesday, March 17, 2021

Previous studies have reported that patients with chronic lymphocytic leukemia (CLL) are at an increased risk of many new malignancies than the general population. However, the mechanisms underlying the risk are unclear. Consistent with previous findings, Henrik Hjalgrim, MD, PhD, of the University of Copenhagen, and colleagues reported that exposure to chemotherapy appeared to be associated with a greater risk of second malignancies. In particular, fludarabine may be associated with an increased risk of myelodysplastic syndrome. The results of the Danish population–based study were published in the British Journal of Haematology.

The researchers identified treated and untreated patients with CLL (n = 4,286) from the Danish National Patient Registry and the Danish National CLL Registry between 2008 and 2017. For each patient with CLL, up to 50 comparators were randomly selected from the general population for 214,150 individuals. Chemotherapy was assigned to about 25% of patients (n = 1,064). Patients were treated with bendamustine-based (n = 210), chlorambucil-based (n = 352), fludarabine-based (n = 310), or other drug regimens (n = 183).

Overall, 594 new malignancies were reported in the patient population, including hematologic (n = 85) and nonhematologic (n = 509) cancers. The most common new malignancies were skin cancer (n = 310), gastrointestinal cancer (n = 88), lower respiratory cancer (n = 85), genital cancer (n = 79), acute leukemia (n = 40), and myelodysplastic syndrome.

The study team found an increased risk of new malignancies among patients with CLL, regardless of the type of treatment. Patients who received chemotherapy tended to be at a higher risk of developing nonhematologic cancers than untreated patients (hazard ratio = 1.29). Of note, patients treated with fludarabine had a significantly higher risk of myelodysplastic syndrome (hazard ratio = 4.93).

Disclosure: For full disclosures of the study authors, visit

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