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Poor prognosis of Hodgkin variant of Richter transformation in chronic lymphocytic leukaemia treated with cladribine ‐ Response to Jamroziak et al

We appreciate the thoughtful comments of Jamroziak and colleagues regarding our study of Hodgkin lymphoma as Richter transformation (Hodgkin-RT) in patients with chronic lymphocytic leukaemia (CLL) (Bockorny et al, 2012). Mirroring our pooled analysis that showed a decreased survival in Hodgkin-RT patients previously treated with fludarabine (0.7 ± 0.2 years), their retrospective analysis demonstrated similarly unsatisfactory outcomes in Hodgkin-RT patients treated with cladribine-based regimens for CLL. Of note, they showed a survival of only 0.34 years (95% confidence interval 0–1.08) in a small cohort of Hodgkin-RT patients whose CLL had previously been treated with cladribine (n = 6). A plausible explanation for this dismal outcome is the marked and prolonged T-lymphocyte depletion caused by the purine nucleoside analogues (PNAs), which amplifies the intrinsic immunosuppression of CLL and possibly leads to reactivation of a latent Epstein-Barr virus infection (Cheson et al, 1999; Dasanu, 2008). In addition, Jamroziak et al hypothesized that the first-line chemotherapy commonly used to treat Hodgkin transformation in CLL might be suboptimal against the PNA-exposed clones. In our cohort, the most commonly employed regimens for Hodgkin-RT therapy were ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), with no statistical difference in overall survival between the two groups. As of today, the best therapeutic approach for Hodgkin-RT remains to be clarified (Tsimberidou et al, 2006). Rituximab with or without chemotherapy remains an attractive option for Hodgkin-RT cases with CD20 Reed-Sternberg cells or marrow/ nodal histologies composed of a mix of Hodgkin lymphoma and CLL. In conclusion, the outcome of the Hodgkin variant of Richter syndrome in CLL, especially when previously exposed to PNAs, should not be viewed as favourable when compared to the classic RT (as diffuse large B-cell lymphoma). Selection of a more intense first-line chemotherapy regimen, with or without targeted antibody therapy may improve the general outcome. Studies aiming to clarify the molecular basis of Hodgkin-RT along with the discovery of innovative therapeutic approaches for this rare variant of RT are awaited.