Variant Richter's syndrome: A rare case of classical Hodgkin's lymphoma developing in a patient with chronic lymphocytic leukemia treated with fludarabine

We report a case of a 52-year-old male who developed classical Hodgkin's lymphoma (HL) four years after diagnosis of stage Rai II (Binet B) chronic lymphocytic leukemia (CLL). The patient was treated with fludarabine and cyclophosphamide with partial response. Subsequently, he presented with a 6-month history of weight loss and fatigue, and 6 weeks of fever, a progressively enlarged liver and elevated serum LDH level. An inguinal lymph node biopsy revealed both classical Hodgkin's lymphoma, nodular sclerosing type grade 2 and CLL. A bone marrow biopsy showed no Reed-Sternberg cells and an infiltrate composed of only scattered small lymphocytes consistent with CLL. Immuno-histochemical studies of the lymph node were consistent with both CLL and HL phenotypes. A cytogenic examination of the bone marrow revealed an abnormal karyotype (Y-) in 15% of the cell population. Treatment with MOPP/ABVD was started and fever subsided within 3 days. Our case is one of the very few descriptions of a rare Richter's variant of CLL with progression to HL in a CLL patient treated with fludarabine. Since fludarabine has become standard therapy in CLL such Richter's variant could be the result of therapy, an induced prolonged and severe immunosuppression. Clinicians should be aware of such association, which could become more frequent among CLL patients treated with purine analogs.