title: Hodgkin's disease variant of Richter's syndrome in chronic lymphocytic leukaemia patients previously treated with fludarabine.
abstract: The transformation of chronic lymphocytic leukaemia (CLL) into large-cell lymphoma (Richter's syndrome, RS) is a well-documented phenomenon. Only rarely does CLL transform into Hodgkin's lymphoma (HL). To further analyse the clinico-pathological and genetic findings in the HL variant of RS, we performed a single-institution study in four patients, who developed HL within a mean of 107 months after diagnosis of CLL. All were treated with fludarabine. Three cases were Epstein-Barr virus (EBV)-associated mixed cellularity (MC) HL, the fourth was nodular sclerosis (NS) HL without EBV association. The sites involved by HL included supra- and infradiaphragmal lymph nodes and the tonsils; stage IV disease was also documented. All patients presented with CLL treatment-resistant lymphadenopathies and B-symptoms. In two of the MC cases, molecular analysis performed on CLL samples and microdissected Hodgkin and Reed-Sternberg cells (HRSC) suggested a clonal relationship, while in NS no indication of a clonal relationship was detected. In summary, HL can occur in CLL patients at any site, up to 17 years after initial diagnosis, especially after treatment with fludarabine. The majority present with B-symptoms and CLL treatment-resistant lymphadenopathy, are of the MC type, clonally related to CLL and might be triggered by an EBV infection.
authors.affiliation: Division of Haematology and Oncology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Dominic
authors.initials: D
authors.lastname: Fong
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaiser
authors.forename: Gilbert
authors.initials: G
authors.lastname: Spizzo
authors.forename: Guenther
authors.initials: G
authors.lastname: Gastl
authors.forename: Alexandar
authors.initials: A
authors.lastname: Tzankov
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002472:Cell Transformation, Viral; D002999:Clone Cells; D019008:Drug Resistance, Neoplasm; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D008297:Male; D008846:Micromanipulation; D008875:Middle Aged; D016539:Reed-Sternberg Cells / Q000648:ultrastructure / Q000821:virology; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D007143:Immunoglobulin Heavy Chains; D014740:Vidarabine; C024352:fludarabine