Bioethical considerations of monoclonal B-cell lymphocytosis: donor transfer after haematopoietic stem cell transplantation.

Monoclonal B-cell lymphocytosis (MBL) is a recently described laboratory finding in otherwise healthy individuals. In MBL, a light chain-restricted, clonal B-cell population, often with a chronic lymphocytic leukaemia (CLL) phenotype, is identified by flow cytometry. Although the prognostic significance remains unclear, there is an increased incidence in ageing populations and those with a family history of CLL. During the past decade of MBL study, three families have come to our attention in which prospective sibling haematopoietic stem cell donors were found to have an MBL. These families raise complex bioethical issues with regard to disclosure of research data, eligibility for clinical trials and potential donor transfer of MBL. These issues are explored in this report. Identification of MBL among prospective sibling transplant donors will become a common occurrence in transplant practice as transplantation is increasingly offered to older individuals and those with CLL.

A natural history of melanomas and dysplastic nevi: an atlas of lesions in melanoma-prone families.

BACKGROUND: Few long-term clinical and histologic data for melanocytic lesions have been available based on the mutation status of families at an increased risk of melanoma. In the current study, the authors describe the clinical and histologic features of dysplastic nevi and melanoma over time in families at an increased risk of melanoma with differing germline mutations in CDKN2A, CDK4, or not yet identified genes. METHODS: Thirty-three families with > 2 living members with invasive melanoma were evaluated clinically and followed prospectively for up to 25 years. All the participants were evaluated by the same study team at the Clinical Center of the National Institutes of Health or in local clinics. After informed consent was obtained, family members (n = 844) were examined and photographed. Blood was obtained for genetic studies; genotyping for CDKN2A and CDK4 was performed. Sequential photographs of melanocytic lesions were taken as part of the clinical evaluations. When melanocytic lesions were removed, the histology was reviewed. Representative photographs and photomicrographs were selected for six classes of lesions and three mutation groups. RESULTS: All the families were found to have members with dysplastic nevi and melanoma; 17 had mutations in CDKN2A, 2 had mutations in CDK4, and 14 had no mutations in either gene identified. The majority of dysplastic nevi either remain stable or regress; few change in a manner that should cause concern for melanoma. With careful surveillance, melanomas can be found early. CONCLUSIONS: The melanomas and dysplastic nevi that were found to occur in the study families did not appear to vary by the type of mutation identified in the families.