Hodgkin lymphoma as Richter transformation in chronic lymphocytic leukaemia: a retrospective analysis of world literature

Abstract

Summary Richter transformation in chronic lymphocytic leukaemia (CLL) represents an entity of considerable genetic, molecular, immunological and clinical heterogeneity. A rare occurrence, Hodgkin variant of Richter syndrome, has not been comprehensively characterized or systematized to date. We conducted a retrospective analysis of the existing cases of Hodgkin lymphoma as Richter syndrome reported in the medical literature in the previous three and a half decades. Our search identified 86 such patients; this entity affects predominantly older men and the most common histological subtype is mixed cellularity. Interval between the diagnosis of CLL and subsequent development of Hodgkin lymphoma is circa 4·3 years. The overall survival of patients was approximately 1·7 years in our analysed cohort. However, our pooled data showed that patients in whom CLL had been treated with fludarabine had a shorter survival after transformation compared to the ones not treated with this agent. The role of immunosuppression and Epstein–Barr virus infection in the aetiopathogenesis of this entity remains to be clarified.

Systemic eosinophilia with skin and pulmonary infiltrates in a patient with chronic lymphocytic leukemia: A case report

“…2% to 8% of patients with B-CLL show progression to a clinical entity known as Richter syndrome/Richter transformation (RS/RT). [20,21] RS/RT most commonly represents progression of CLL into diffuse large B-cell lymphoma (DL-BCL), [22,23] and should be suspected when rapid clinical deterioration, fever in absence of infection, and rapidly enlarging lymphadenopathy appear in a patient with CLL. [20] In a cohort study of newly diagnosed patients with CLL between 2000 and 2011 at Mayo Clinic, the incidence of RS/RT was 2.3%.…”

“…[20,21] RS/RT most commonly represents progression of CLL into diffuse large B-cell lymphoma (DL-BCL), [22,23] and should be suspected when rapid clinical deterioration, fever in absence of infection, and rapidly enlarging lymphadenopathy appear in a patient with CLL. [20] In a cohort study of newly diagnosed patients with CLL between 2000 and 2011 at Mayo Clinic, the incidence of RS/RT was 2.3%. [24] According to retrospective data, development of CLL into HL (termed Hodgkin variant of Richter transformation, HvRT) occurs in 0.4% of patients with CLL with a male predominance.…”

“…[19,25] Two types of HvRT have been postulated: [26] In type 1 transformation, HRS-like cells are interspersed with CLL lymphocytes without the typical inflammatory background of HL. [20,[25][26][27][28] Clonality studies demonstrate heterogeneous results showing clonal relationship in some of the cases. [6,29] In contrast, type 2 transformation is characterized by the occurrence of classical HL with HRS cells intermingled in the characteristic inflammatory background infiltrate separately from the CLL cells.…”

“…Molecular analyses provide evidence in many cases for separate clonal origins of both tumors supporting development of HL as a distinct second malignancy. [20,26,30,31] While different pathogenetic mechanisms are discussed in both types of transformation, only type 2 is considered as true Hodgkin transformation irrespective of clonal relationship with the underlying CLL cells. [6,20,[29][30][31][32] In our patient, morphological and immunohistochemical findings at autopsy showed classical HL, namely type 2 transformation.…”

“…[46] When multiagent chemotherapy is administered, overall response rates of around 50% and short progression-free intervals have been reported. [20,25] Generally, clinical outcomes are worse than in de novo HL. [20,25,32] A retrospective analysis demonstrated that patients previously treated for CLL with fludarabine displayed a more aggressive course of HL and a shorter mean survival of 0.7 years compared to 2.1 years in the non-fludarabine group.…”