Patients with chronic lymphocytic leukemia (CLL) who progress with lymphadenopathy after frontline treatment may experience inferior clinical outcomes compared with patients who progress with increasing absolute lymphocyte count (ALC), according to recent analysis of data from the German CLL Study Group (GCLLSG) published in the American Journal of Hematology.

Progressive disease (PD) in CLL after remission from frontline therapy can be phenotypically heterogeneous. To assess whether mode of PD is associated with clinical outcomes, researchers examined data from 3 phase 3 clinical trials from the GCLLSG ( Identifiers: NCT00281918, NCT00769522, NCT01010061). The trials included 2159 patients who received chemotherapy or chemoimmunotherapy.

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In total, 241 patients experienced PD with increasing ALC, and 727 patients experienced PD with lymphadenopathy; 329 patients progressed with both increasing ALC and lymphadenopathy.

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In fit patients, median time to next treatment (TTNT) after PD with lymphadenopathy was 12.3 months compared with 17.0 months in the increasing ALC group (hazard ratio [HR], 1.299; 95% CI, 1.036-1.628; P =.024). Median overall survival (OS) after PD was not significantly different between the 2 groups; in patients with lymphadenopathy, median OS was 45.1 months compared with 42.4 months in patients with increasing ALC (HR, 1.023; 95% CI, 0.753-1.389; P =.885).

In unfit patients, median TTNT after PD with lymphadenopathy was 11.7 months and PD with increasing ALC was 21.4 months (HR, 1.357; 95% CI, 1.051-1.753; P =.019).

Median OS was significantly different between the 2 groups in unfit patients. In unfit patients with lymphadenopathy, median OS was 42.8 months, whereas in unfit patients with increasing ALC, median OS was not reached (HR, 1.851; 95% CI, 1.280-2.677; P =.001).

Of note, patients who progressed with both lymphadenopathy and increasing ALC experienced especially poor clinical outcomes, with median TTNT of 10.6 months in fit patients and 10.5 months in unfit patients. In this group of patients, median OS was 43.5 months in fit patients and 42.8 months in unfit patients.

The authors concluded that “the results suggest that progression by lymphadenopathy is associated with a less favorable clinical course, in particular in unfit patients with CLL. This might help physicians in managing their patients and researchers in designing future clinical trials.”


1. Al-Sawaf O, Bazeos A, Robrecht S, et al. Mode of progression after first line treatment correlates with outcome of chronic lymphocytic leukemia (CLL) [published online June 20, 2019]. Am J Hematol. doi:10.1002/ajh.25561