Plasmablastic lymphoma (PBL) is an aggressive lymphoma characterized by a terminally differentiated B-cell phenotype that usually occurs in the immunocompromised or elderly patients. Although the clinical and pathologic characteristics of these tumors have been defined, the genetic alterations involved in their pathogenesis are not well known. In this study, we have investigated the chromosomal alterations of MYC, BCL2, BCL6, MALT1, PAX5, and IGH loci using fluorescence in situ hybridization in 42 PBL and 3 extracavitary primary effusion lymphomas. MYC rearrangements were identified in 20 of 41 (49%) PBL and the immunoglobulin (IG) genes were the partners in most tumors. MYC rearrangements were more common in Epstein-Barr virus (EBV)-positive (14 of 19, 74%) than EBV-negative (9 of 21, 43%) tumors (P50 mo) had no or low number of gains (<3). No rearrangements of any of these loci were seen in the primary effusion lymphomas. In conclusion, PBL are genetically characterized by frequent IG/MYC translocations and gains in multiple chromosomal loci. The oncogenic activation of MYC in these lymphomas may be an important pathogenetic element associated with EBV infection.

Purpose: To define the clinical and pathologic characteristics of primary cutaneous small/medium CD4⁺ T-cell lymphoma (PCSM-TCL) and identify parameters of prognostic significance. Patients and Methods: We have investigated 24 patients with primary cutaneous lymphomas composed of small/medium mature T-cells with a βF1, CD3, CD4⁺ and/or noncytotoxic, CD8^– and CD30^– phenotype. The proliferation index and CD8⁺ infiltrating cells were quantified with an automated image analysis system. Results: Sixteen patients presenting with solitary or localized plaques or small nodules (< 3 cm) had an indolent course. Only three patients experienced repeated cutaneous relapses, and none of them died as a result of the disease after 1 to 168 months (median, 17 months) of follow-up. The tumors had a low proliferation (median Ki-67, 9% ± 5%) and an intense infiltrate of reactive CD8⁺ (median, 20% ± 11.7%). Five patients presenting with rapidly evolving large tumors or nodules (≥ 5 cm) had an aggressive disease and died with extracutaneous dissemination 18 to 36 months after diagnosis (median, 23 months). These tumors had a significantly higher proliferation (median Ki-67, 22% ± 11.3%; P < .05) and lower number of infiltrating CD8⁺ (median, 1% ± 3%; P < .05) than the previous group. A third group of three patients had a peculiar clinical presentation with multifocal relapsing lesions without extracutaneous dissemination after a long period of follow-up ranging from 41 to 92 months. Histologically, these cases had an intense infiltrate of eosinophils. Conclusion: PCSM-TCL is a heterogeneous group of tumors with differentiated clinical and pathological characteristics with impact in the outcome of the patients.

MicroRNAs (miRNAs) are negative regulators of gene expression that play an important role in hematopoiesis and tumorigenesis. We analyzed miRNA expression in classic Hodgkin lymphoma (cHL) and the influence of Epstein-Barr virus (EBV) infection on the miRNA expression profiles. The expression of 157 miRNAs in lymph nodes from 49 cHL patients and 10 reactive lymph nodes (RLNs) was analyzed by real-time polymerase chain reaction (PCR). Hierarchic clustering revealed 3 well-defined groups: nodular sclerosis cHL, mixed cellularity cHL, and RLNs. A distinctive signature of 25 miRNAs differentiated cHL from RLNs, and 36 miRNAs were differentially expressed in the nodular sclerosis and mixed cellularity subtypes. These results were validated in a set of 30 cHLs and 5 RLNs, and in 3 cHL cell lines. miR-96, miR-128a, and miR-128b were selectively down-regulated in cHL with EBV. Our findings suggest that miRNAs play an important role in the biology of cHL and may be useful in developing therapies targeting miRNAs.

Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this treatment available to our patients prompted us to develop a novel CART19 based on our own anti-CD19 antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- and CD3z-signaling domains. We show that A3B1 CAR T cells are highly cytotoxic and specific against CD19+ cells in vitro, inducing secretion of pro-inflammatory cytokines and CAR T cell proliferation. In vivo, A3B1 CAR T cells are able to fully control disease progression in an NOD.Cg-Prkdc scid Il2rd tm1Wjl /SzJ (NSG) xenograph B-ALL mouse model. Based on the pre-clinical data, we conclude that our CART19 is clearly functional against CD19+ cells, to a level similar to other CAR19s currently being used in the clinic. Concurrently, we describe the implementation of our CAR T cell production system, using lentiviral vector and CliniMACS Prodigy, within a medium-sized academic institution. The results of the validation phase show our system is robust and reproducible, while maintaining a low cost that is affordable for academic institutions. Our model can serve as a paradigm for similar institutions, and it may help to make CAR T cell treatment available to all patients.

Key Points: PTFL is a monoclonal B-cell neoplasia with low genomic complexity and recurrent TNFRSF14 mutations/deletions. The genetic profiles of conventional t(14;18)− and t(14;18)+ FL are similar but distinct from PTFL.