Transformation of Chronic Lymphocytic Leukemia into Hodgkin’s Disease The M D Anderson Cancer Center Experience.

Introduction: Hodgkin’s disease (HD) is a rare complication of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Outcome in patients with HD following CLL/SLL is thought to be inferior to that of patients with de novo HD and superior to that of patients with Richter’s syndrome (RS), but data are lacking. The purpose of this study was to assess the incidence, presenting characteristics, and clinical outcomes of HD.

Methods: An electronic database search of patients with CLL/SLL who presented at U.T. M. D. Anderson Cancer Center Department of Leukemia between 1975 and 2005 was performed, and patients who developed HD were identified.

Results: Among 3986 patients with CLL/SLL, 13 patients (0.3%) developed HD. Patients with HD presented with B symptoms (62%), lymph node enlargement (46%), splenomegaly (15%), hepatomegaly (8%), hypercalcemia (8%), thrombocytopenia (8%), and infection (8%). The median age was 72 years (range, 49–81 years). There were 11 men (85%). The median time from CLL/SLL to HD was 5.0 years (range, 1.8–12.9 years). HD was confirmed by biopsy of involved lymph nodes (46%), bone marrow (38%), spleen (8%), or buccal mucosa (8%). All patients were previously treated for CLL/SLL. Nine patients had received >1 prior therapies. Prior therapies included fludarabine +/− cyclophosphamide +/− rituximab (85%), chlorambucil (31%), rituximab (23%), alemtuzumab (15%), platinum-based combination regimens (15%), or other therapies (38%). At presentation of HD, the median β₂-microglobulin levels were 4 mg/dL (range, 2.2–11.5 mg/dL) and the median lactate dehydrogenase levels were 717 IU/L (range, 336–1883 IU/L). Cytogenetics were as follows: normal, 4 (44%) of 9 patients; -Y, 3 patients; 11q-, 1 patient; and complex including del(13)(q14q22) and trisomy 12, 1 patient. Epstein-Barr virus (EBV) was positive by in situ hybridization in 3 (75%) of 4 tested patients. Ten (77%) of 13 patients were treated with chemotherapy for HD. Five patients were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), 2 patients were treated with cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP), 1 patient with CVPP/ABVD, 1 patient with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and 1 patient with fludarabine, cytarabine, cyclophosphamide, and cisplatin (FACP). One patient was treated with cidofovir, and the other 2 patients received no therapy. The overall response rate was 60%. Responses were noted in patients treated with ABVD (complete remission [CR], 1; partial remission [PR], 2), CVPP (CR, 1), CVPP/ABVD (PR, 1), and CHOP (PR, 1). The median overall survival duration was 0.8 years (95% C.I., 0.4 – 6.7⁺ years). The median failure-free survival (FFS) duration was 0.4 years (95% C.I., 0.2 – 6.7⁺ years).

Conclusions: These data suggest that the response to treatment, survival, and FFS of patients with HD following CLL are inferior to that reported in patients with de novo HD. These outcomes, as well as the presenting characteristics of HD following CLL/SLL, are similar to those reported for patients with RS.