title: EBV negative Richter's syndrome from a coexistent clone after salvage treatment with alemtuzumab in a CLL patient.
abstract: Transformation of B cell chronic lymphocytic leukemia (B-CLL) to large cell lymphoma or Hodgkin's disease is known as a Richter's syndrome (RS). According to the literature, 1-10% of B-CLL patients develop this high-grade lymphoid malignancy. The relationship between the immunosuppressive effect of nucleoside analogues (NA) and monoclonal antibodies and the development of large cell transformation still remains a controversial issue. We describe a CLL patient who developed a large B cell lymphoma 94 months after diagnosis and 3 months after the start of alemtuzumab. The CLL immunophenotype was retained by the transforming cells although a different light chain was expressed. Molecular analysis of the immunoglobulin heavy chain confirmed that the CLL and the RS had a different clonal origin. Subsequent molecular analyses of stored samples showed that the clone with transforming capacity already appeared two years before the clinical appearance of the RS. We hypothesize that alemtuzumab promoted the uncontrolled growth of the latest clone by eradicating the initial B-CLL clone efficiently, and by inducing a strong T cell depletion with consequent impairment of the immunosurveillance. We also ruled out that the RS was EBV driven. In conclusion, we report a case of EBV negative RS after alemtuzumab as salvage therapy.
authors.affiliation: Department of Hematology, Ghent University Hospital, Ghent, Belgium. ann.janssens@uz.kuleuven.be
authors.forename: Ann
authors.initials: A
authors.lastname: Janssens
authors.forename: Mario
authors.initials: M
authors.lastname: Berth
authors.forename: Pascale
authors.initials: P
authors.lastname: De Paepe
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.forename: Lucien
authors.initials: L
authors.lastname: Noens
authors.forename: Jan
authors.initials: J
authors.lastname: Philippé
authors.forename: Fritz
authors.initials: F
authors.lastname: Offner
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000473:pathology; D002999:Clone Cells / Q000473:pathology; D020031:Epstein-Barr Virus Infections / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000139:chemically induced / Q000473:pathology* / Q000821:virology; D008875:Middle Aged; D013577:Syndrome; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab