Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in which familial aggregation has been observed. The affected relative is usually a sibling and less frequently a child. In the present study we evaluated whether CLL affecting parents and their children was associated with different clinical features, survival, immunoglobulin (Ig) VH genes repertoire and mutation status. The family history of 2% of the CLL patients diagnosed at our institution was characterized by the presence of a parent or a child affected by CLL. Other lymphoproliferative diseases, such as non-Hodgkin lymphoma, Hodgkin disease and acute lymphoid leukemia, affecting parents or children were also recorded in 3% of cases. Among the 17 identified parent/child CLL pairs there was a higher, though not significant, rate of gender concordant pairs than expected. Children were significantly younger at diagnosis than their parents. No significant differences in stage distribution, clinical course, survival and proportion of unmutated cases emerged between the two generations. In no case the parent and the respective child shared an identical IgVH repertoire. However, a significantly higher than expected usage of VH3-23 (p<0.005), VH3-21 (p<0.005), VH5-51 (p=0.001), VH1-18 (p= .90E-04), VH3-30.3 (p<0.005) genes was recorded. Of interest, a VH5-51 gene usage has been also described by other authors in multiaffected families. By flow cytometry and PCR analysis, no clonal lymphocytes were found in the peripheral blood of 38 young healthy (median age: 37 years) relatives included in the third generation of these multiply affected families. This could be explained not only by the relatively small sample of subjects analyzed but also by their relatively younger age compared to that of the healthy individuals analyzed in other series. In conclusion, the coexistence of CLL in parents and offspring is a relatively uncommon event. The differences in the IgVH gene repertoire could reflect a different ontogeny of these cases. Affected children show a significantly earlier, but not a more aggressive clinical course. These data can be used to offer counselling to CLL patients.

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