Large B-cell transformation in nodular lymphocyte-predominant Hodgkin lymphoma: 40-year experience from a single institution.

A number of reports have shown a propensity of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) to transform into diffuse large B-cell lymphoma (DLBCL). Long-term data on the incidence and outcomes of transformed NLPHL are lacking. A comprehensive analysis of the actively maintained Mayo Clinic Lymphoma Database was performed. Between 1970 and 2011, 222 consecutive adult patients with new untreated NLPHL were identified. Median age at diagnosis was 40 years, and 146 (66%) were males. The median follow-up was 16 years. Seventeen patients (7.6%) developed a transformation to DLBCL. The median time to transformation was 35 months (range, 6-268 months). Based on the observed 17 transformations during 2304 patient-years of follow-up, the rate of transformation was 0.74 per 100 patient-years. In a multivariate analysis, use of any prior chemotherapy ( ITALIC! P= .04) and splenic involvement ( ITALIC! P= .03) were significantly associated with increased risk of transformation. The 5-year overall survival (OS) in those with transformed disease was 76.4%, and transformation did not adversely affect OS when compared with patients who did not experience transformation. In this large single-institution cohort with long-term follow-up, the risk of transformation was lower than that observed in other low-grade lymphomas.

Chimeric antigen receptor T-cell therapy to target hematologic malignancies.

Several decades of humoral immunotherapy using monoclonal antibodies and cellular immunotherapy using hematopoietic cell transplantation have recently culminated in a successful merger: the development and clinical application of genetically engineered antibody-T cell chimeras. Also known as chimeric antigen receptor T cells (CAR T cells), these entities combine the exquisite antigen specificity of antibodies with the polyfunctionality and potency of cellular immunity and are a prime example of the potential for synthetic biology to treat disease. CAR T cells overcome several of the biologic obstacles that have historically hampered immunotherapy while providing fundamental mechanistic insights into cellular immunology and revealing new challenges in genetic engineering and target selection. Results from early-phase CAR T-cell-based clinical trials demonstrate the significant potential for this approach to affect dramatic and complete clinical responses while revealing novel toxicities associated with activation of potent and specific antitumor immunity.