Reversible lymph node follicular hyperplasia associated with dasatinib treatment of chronic myeloid leukemia in chronic phase.

Dasatinib is a tyrosine kinase inhibitor licensed in the treatment of chronic myeloid leukemia (CML) known to exert immunomodulatory effects in vitro and in vivo.We report on 9 chronic phaseCMLpatients who developed follicular lymphoid hyperplasia (FLH) apparently caused by dasatinib, an unreported adverse event related to this drug. Patients received dasatinib at 100 mg (n5 7), at 80 mg (n5 1), or at 50 mg (n5 1) daily for chronic phase CML, either frontline as part of the Optimized Tyrosine kinase Inhibitors Monotherapy (OPTIM) dasatinib trial (EudraCT number 2008-006854-17) (n5 2) or after intolerance (n5 2), or suboptimal response/resistance (n 5 5) to imatinib. From our first line patients included in the prospective academic OPTIM dasatinib trial, the estimated order of frequency of FLH might be 0.7% (2 of 291). Sex ratio of female to male was 3:6. Sokal scores were low (n5 2), intermediate (n5 1), and high (n5 6). Median age at FLH diagnosis was 52 years (range, 24-69 years). All patients presented with progressive cervical lymph node enlargement after median treatment duration of 20 months (range, 9 to 35 months). One patient presented additionally inguinal lymph node enlargement. At the time of discovery, 8 patients were in complete cytogenetic response associated with a major molecular response (n 5 3) or with a complete molecular response (n 5 3). Clinical examination revealed no local or systemic infectious disease. Toxoplasmosis, viral and autoimmune disorders assessments failed to show any active disease. Tomodensitometry confirmed absence of additional localization. In 1 patient, nodes enlargement was associated with peripheral lymphocytosis related to an increase of natural killer cells and CD8 T-cells, but not to B-cells, as previously described. All patients underwent a lymph node biopsy that revealed an FLH (Figure 1A), and an extramedullary blastic transformation of CML was ruled out. Lymph node immunostaining showed a follicular reactive phenotype CD10 Bcl2 (see Figure 1B). Cytogenetic analysis of lymph node revealed in 1 patient as clonal abnormality (Figure 1C) without IGH/BCL2 rearrangement detected by standard fluorescence in situ hybridization (data not shown) and clonality assessment showed a DJ-JH rearrangement (Figure 1D). However, the frequency of rearrangement could be underestimated because clonality was searched only in some patients, but not all,