Clonal relationship of classical hodgkin lymphoma and its recurrences

We investigated whether the first and all subsequent manifestations of Hodgkin lymphoma (HL) in a patient are clonally related.

We identified a collective of 20 patients with sometimes multiple HL recurrences. Relapses were classified as early, that is, within twelve months (eight events in seven patients) or as late, that is, later than one year after the previous neoplasm (24 events in 17 patients). Hodgkin and Reed-Sternberg cells were microdissected after CD30 staining using laser capture technique. Immunoglobulin heavy chain (IgH) gene fragment lengths were analyzed after DNA preamplification, applying consensus FR3 and J primers by ABI 310 Genetic Analyzer. Sequencing of the amplified IgH products was carried out by ABI 3130 and 3730XL Genetic Analyzer. Epstein-Barr virus (EBV) association was assessed by EBV early RNA and LMP1.

Three cases with early relapses after a first HL diagnosis were clonally related to the initial tumor, whereas three of four patients with early relapses after a first or second relapse were not, which was accompanied by change of EBV association in one case. Six patients presenting with late relapses were clonally unrelated, which was accompanied by change of phenotype in two cases and change of EBV association in one case. Two samples from recurrent tumors of the same patient could be successfully sequenced. These two late relapses were clonally unrelated by IgH fragment length and sequencing analysis.

Recurrent HL, especially those accompanied by an EBV-association switch or after a relapse, can represent an unrelated novel neoplasm. Our finding might play a role in clinical decision making.