Aberrant T-Cell Antigen Expression in Classical Hodgkin Lymphoma Is Associated with Decreased Event-Free Survival (EFS) and Overall Survival (OS).
Girish Venkataraman, Alexandra Traverse-Glehen, Joo Y Song, Franziska C Eberle, Jeffrey C Hanson, Stephan Dirnhofer, Alexander Tzankov, Georg Heinze, Mark A Raffeld, Stefania Pittaluga, Elaine S Jaffe. National Cancer Institute, Bethesda, MD; Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France; University Hospital, Basel, Switzerland; Medical University of Vienna, Austria
Background: The neoplastic Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) have been reported rarely to express T-cell associated antigens (TCA), but the clinical significance of this finding is uncertain.
Design: 51 cases of cHL expressing any TCA on the HRS cells (T-cHL) were identified in two cohorts (NCI, n=39; Basel n=12). The diagnostic immunomorphologic features were examined in all cases with additional PCR studies for T-cell clonality performed in a subset of cases (n=22, NCI; n=10, Basel). The outcome data were compared with a cohort of cHLs negative for TCA (n=272). Primary endpoints examined were event-free survival (EFS) and overall survival (OS). Data were examined using proportional hazards regression.
Results: The median age in the T-cHL group was 40 yrs (range: 10-85). Seventy percent (23/33) were in low stage (stage I/II) at presentation. In 41/51 cases (80%), the biopsy showed nodular sclerosis (NS) histology with NS2 predominating in 68%. The HRS cells expressed CD30 (100%), CD15 (76%) and PAX-5 (77%). Among TCA, CD4 and CD2 were most commonly expressed, seen in 37/47 (78%) and 25/32 (77%) cases respectively. ALK was negative in all 14 tested cases. In 21/22 NCI cases, PCR did not show a T-cell clone (including two wherein single HRS cell microdissection was additionally performed). However, 2/10 microdissected T-cHLs from the Basel cohort evidenced a T-cell clone. During a median follow up of 113 months, 11 deaths (0.08/patient-year) and 17 events (0.14/pt-yr) were observed in the T-cHL group vs. 0.02 deaths/pt-yr and 0.049 events/pt-yr in TCA-negative group. In the outcome analyses, TCA expression predicted shorter OS (HRadj=3.23[95%CI: 1.57, 6.62]; p=0.0015) and EFS (HRadj=2.37[95%CI: 1.33, 4.21]; p=0.0033). These outcome differences remained significant even when analysis was restricted to the NS subgroup.
Conclusions: T-cHL often display NS histology at presentation and lack a T-cell genotype in most instances. They are associated with significantly shorter OS and EFS compared to TCA-negative cHLs. These data support the inclusion of additional TCA staining at diagnosis in the NS subgroup of cHL to aid in better risk stratification.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 155, Tuesday Afternoon