“Double Hit”High-Grade B-Cell Lymphomas: An Aggressive Disease with Heterogeneous Histologic Features and Clinical Outcome.
Shaoying Li, L Jeffrey Medeiros, Luis E Fayad, Patrick A Lennon, C Cameron Yin, Pei Lin. The University of Texas MD Anderson Cancer Center, Houston
Background: B-cell lymphomas with concurrent IGH-BCL2/t(14;18)(q32;q21) and MYC/8q24 rearrangement, also known as “double hit” B-cell lymphomas, are rare tumors. Here we review our experience with these tumors.
Design: The study group represents all cases of "double hit" B-cell lymphoma from 1995 to 2010 confirmed by fluorescence in situ hybridization (n=25) and/or conventional cytogenetic analysis (n=19). Patient survival was analyzed using the Kaplan-Meier method and compared using the log-rank test.
Results: The study group included 36 patients, 26 men and 10 women, with a median age of 55 years (range, 18 to 76 years). Twenty-nine (81%) patients presented de novo and 7 (19%) patients had a history or concurrent low-grade follicular lymphoma (FL). Twenty (62%) patients had two or more extranodal sites of disease. Bone marrow and central nervous system (CNS) involvement were observed in 20/35 (57%) and 7/19 (37%) cases, respectively. At diagnosis, 27/34 (79%) patients with available data had an elevated serum LDH level. According to the WHO classification, mophologically there were 19 high-grade B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL), 12 DLBCL, 3 BL, 1 B-lymphoblastic lymphoma, and one high-grade FL with focal DLBCL. CD10 and BCL2 were expressed in 33/34 (97%) and 30/35 (86%) cases, respectively. Cytogenetic analysis showed a complex karyotype in all 19 cases analyzed. Each patient was treated with combination chemotherapy including R-CHOP (n=19) and more aggressive regimens (n=23). After a median follow up of 48.7 months (range, 1.4 – 82.1 months), 21 patients died and 11 remained in remission. The median overall survival (OS) was 13.7 months and the 1 year survival rate was 53%. Univariate analysis showed that de novo disease, normal serum LDH, < 2 extranodal sites of involvement, absence of bone marrow disease, absence of CNS involvement, and stage I/II disease were associated with a better prognosis (P<0.05). The median OS of patients with a previous or concurrent FL was 7.4 months compared with 48 months for patients with de novo presentation.
Conclusions: “Double hit” high-grade B-cell lymphomas are clinically highly aggressive tumors that exhibit a spectrum of morphologic findings. Extranodal spread including bone marrow and CNS involvement is frequent. There were a number of poor prognostic factors in this patient cohort, however, a history of or concurrent FL appears to identify a subset of patients with a particularly poor prognosis.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 217, Wednesday Afternoon