Anti-CD52 monoclonal antibody

Antithymocyte globulin (ATG)-based immunosuppression remains the standard immunosuppressive therapy (IST) for aplastic anemia (AA) patients lacking a sibling donor; however, treatment failures are relatively frequent, including about one-quarter to one-third of patients who do not show any response to initial IST, and about half of the initial responders who may experience subsequent relapses or require continuous maintenance IST. For these patients, there is the option of further IST, which may include additional courses of ATG-based IST, or attempts with alternative IST regimens. Alemtuzumab is a monoclonal anti-CD52 Ab, which has been recently investigated as novel IS agent for the treatment of AA patients. Recent data from different groups have clearly demonstrated the biological efficacy of Alemtuzumab in AA patients, ruling out the initial concerns about possible unacceptable infectious risks secondary to its extremely powerful lympholytic effect. Preliminary data demonstrate a remarkable efficacy, especially in the context of relapsed and, to less extent, refractory patients, whereas data in naive patients are still limited. On the basis of these results, Alemtuzumab-based immunosuppression is a worthy option for AA and other marrow failure patients requiring a second-line IST. Here we describe, a consensus regimen that the European Group for Blood and Marrow Transplantation Severe Aplastic Anemia Working Party suggests for AA patients failing initial IST who are not indicated for SCT. Bone Marrow Transplantation (2013) 48, 186-190; doi:10.1038/bmt.2012.245; published online 10 December 2012

CTCL follows different courses depending on the clinical stage at the time of diagnosis. Patients with early stage Mycosis Fungoides (MF) variant of CTCL may experience an indolent course over decades, whereas patients with advanced MF and Sezary Syndrome (SS) disease at diagnosis, often succumb within 5years. Even within early stage CTCL/MF, a minority of patients will progress to more advanced stages. We recently generated RNA sequencing data on 284 CTCL-relevant genes for 157 patients and identified differentially expressed genes across stages I-IV. In this study, we aim to validate robust molecular markers linked to disease progression and survival. We performed multiple hypothesis testing-corrected analysis of variance (ANOVA) on the expression of individual genes across all CTCL samples and early stage (<= IIA) CTCL/MF patients. We used in silico immune cell-type deconvolution from gene expression data to estimate immune cell populations. Based on the analysis of all CTCL samples, we identified TOX, FYB, and CD52 as predictors of disease progression and poor survival. Among early stage (<= IIA) CTCL/MF patients, these 3 genes, along with CCR4, were valuable to predict disease progression. We validated these 4 genes in 3 independent, external Sezary Syndrome patient cohorts with RNA-Sequencing data. In silico immune cell-type deconvolution revealed that neutrophil infiltration in early stage MF conveyed a higher risk for disease progression. Also, NK cell infiltration in late stage MF/SS correlated with improved survival. TOX, FYB, CCR4 and CD52 are robust disease progression and decreased survival biomarkers in CTCL.