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Gray-zone lymphoma (GZL) reflects an aggressive B-cell neoplasm with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). The International Prognostic Index (IPI) and its derivatives (R-IPI, NCCN-IPI, and the Hasenclever IPS) have been established for DLBCL or cHL while the most suitable scoring system for GZL remains undetermined. In an exploratory multi-centric cohort of GZL (n = 61), we performed a comparative analysis of prognostic indices with regard to model fit and mutual concordance. The calculation of the corrected Akaike's information criterion (cAIC) and Harrel's concordance index (c-index) for each scoring system identified the NCCN-IPI to harbor the most convincing prognostic capabilities regarding both overall survival (OS) and progression-free survival (PFS) compared to its enhanced derivatives. The current results affirm the clinical utility of the NCCN-IPI and suggest its preferential use in clinical practice in GZL-patients. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to exploring whether single nucleotide polymorphism (SNP) will be clinical outcome predictive in multiple myeloma (MM) or not, using autologous stem cell support and high-dose melphalan. Topics discussed include assumption of polygenic phenomenon for MM risk; treatment of patients with thalidomide monotherapy; and use of SNP in TP53 is predictive of clinical outcome in MM.

A letter to the editor is presented regarding the study on the prognostic impact of RAS mutations on clinical outcome of patients with multiple myeloma who were treated with high-dose melphalan and autologous stem cell transplantation.

Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma (DLBCL) of the elderly constitutes a provisional clinicopathological entity in the current World Health Organization (WHO) classification and its genomic features remain sparsely characterized. We investigated a cohort of 26 cases of untreated de novo EBV-positive DLBCL of the elderly by high-resolution array-based comparative genomic profiling and fluorescence in situ hybridization (FISH). Moreover, we screened for activating mutations affecting nuclear factor (NF)-κB pathway signaling and chromatin remodeling (EZH2, CD79B, CARD11 and MYD88) due to their impact of gene expression signatures and postulated upcoming therapeutic targetability. We identified an overlap between genomic aberrations previously described to be exclusive features of plasmablastic lymphoma (PL), post-transplant lymphoproliferative disorder (PTLD) and DLBCL, respectively, indicating a close cytogenetic relationship between these entities. Few mutations affecting CD79B and CARD11 and no MYD88 mutations were detectable, hinting at EBV-mediated activation of NF-κB as an alternative to pathologically enforced B-cell receptor signaling in this rare entity. [ABSTRACT FROM AUTHOR]

Double-hit lymphomas (DHL) with MYC and either BCL2 or BCL6 rearrangements are rare neoplasms with an aggressive clinical presentation and grim prognosis. Moreover, molecular characterization of DHL remains insufficient, and especially the role of TP53 pathway disruption is unknown. We employed a next-generation sequencing approach to investigate the mutational status of TP53 in DHL and correlated genomic data with immunohistochemical reactivity for p53. We identified TP53 mutations in MYC+/BCL2+ lymphomas at a frequency intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Remarkably, TP53 mutations were particularly scarce in MYC+/BCL6+ lymphomas. Our findings indicate a significant difference between these two types of DHL at a molecular level with pathogenetic implications, as arguably, TP53 mutations inhibiting p53 mediated promotion of apoptosis pose a synergistic advantage in clonal evolution of cells with malignantly enforced overexpression of BCL2. Immunohistochemical staining appears to be a sensitive surrogate of TP53 mutation status with moderate specificity. [ABSTRACT FROM AUTHOR]