High frequency of unrecognized indolent hematological disorders among HLA-matched siblings of patients with lymphoproliferative malignancies eligible for allo-SCT

摘要

Since 2004, 19 patients with relapsed CLL and non-Hodgkin's lymphoma have been included in a phase II trial of allo-SCT from HLA-matched sibling donors. The donor screening includes all HLA-matched siblings in the sibship with a full-scale search by means of BM morphology, flow cytometry and clonality (Ig and TCR) testing to exclude subclinical malignant hematological diseases.An unexpectedly high frequency of malignant hematological diseases was detected: An otherwise healthy sibling was found to have a hematological disorder in 5 of the 19 families (26%; Figure 1). There were four cases of concordant lymphoproliferative disease (two large granular T-lymphocytic leukemia and two marginal zone lymphoma) and one case of myeloproliferative disease (JAK2 + essential thrombocytosis). This remarkably high frequency is in accordance with the concept of clustered familiallymphoproliferative disease (LPD), and in keeping with a recent survey, which placed the myeloproliferative disease within this pleiotypic entity.5 There was a male-male sex concordance in three of the families (Figure 1; families 2, 3 and 4) and a sister-brother concordance in two families (Figure 1; families 1 and 5), but a marked male excess of affected siblings (eight males and two females).