Hodgkin's lymphoma as a unique variant of Richter syndrome.

progression in lymphadenopathy, the appearance/worsening of “B” symptoms, and elevated levels of lactate dehydrogenase, as well as histological features requiring a new tissue biopsy. The incidence of Richter syndrome in patients with CLL is 2% to 9%. Most frequently, CLL transforms into diffuse large B cell lymphoma, while in only 0.4% of patients will CLL transform to Hodgkin’s lymphoma [4]. In the current issue of IMAJ, Zavdy et al. [5] describe a 53 year old CLL patient who was diagnosed with Hodgkin’s lymphoma as a rare variant of Richter syndrome. In the classic Richter syndrome, the large B cells of the lymphoma are usually clonally related to the CLL, representing a true transformation of the indolent disease into an aggressive phase [6]. The Hodgkin variant of Richter syndrome, in contrast, is almost always unrelated to the CLL clone. Nevertheless, since the incidence of Hodgkin’s lymphoma among patients with CLL is approximately eight times higher than in the general population [7], this suggests a causal relationship between the two diseases. The case described by Zavdy et al. raises another interesting question: the role of fludarabine in the course and development of Richter syndrome. CLL has an inherent immune-suppressive nature, which can be further augmented by chemotherapy. This immune suppressive state is considered a plausible pathobiological explanation for the increased risk of Hodgkin’s lymphoma among CLL patients. Studies that evaluated Epstein-Barr virus status in Hodgkin’s transformation of CLL, either by staining for latent membrane protein 1 (LMP1) on immunohistochemistry or by in situ c hronic lymphocytic leukemia is the most common type of adult leukemia in western countries. The clinical course of CLL1 patients is heterogenic. While some patients enjoy an almost normal life expectancy, others will suffer from a steep downhill course [1]. In the past, patient prognosis was based on clinical staging, but today the ability to predict the clinical outcome of patients with CLL has improved with the use of novel prognostic factors such as specific cytogenetic abnormalities, serum beta-2 microglobulin levels, immunoglobulin variable heavy chain mutation status, CD38 positivity and ZAP 70 positivity [2]. A fludarabine-containing chemoimmunotherapy regimen was shown to improve progression-free survival and overall survival in CLL and became the standard frontline therapy for physically fit patients [3]. Since CLL patients live longer, there is growing interest in the long-term adverse outcome of the disease and in the possible role that specific chemotherapy agents may have in promoting them. This includes Richter transformation. The transformation of CLL into an aggressive lymphoma was first described by M.N. Richter in 1928. Richter syndrome involves an aggressive clinical course that consists of sudden