Purpose Adult T-cell leukemia-lymphoma (ATL) is a distinct mature T-cell malignancy caused by chronic infection with human T-lymphotropic virus type 1 with diverse clinical features and prognosis. ATL remains a challenging disease as a result of its diverse clinical features, multidrug resistance of malignant cells, frequent large tumor burden, hypercalcemia, and/or frequent opportunistic infection. In 2009, we published a consensus report to define prognostic factors, clinical subclassifications, treatment strategies, and response criteria. The 2009 consensus report has become the standard reference for clinical trials in ATL and a guide for clinical management. Since the last consensus there has been progress in the understanding of the molecular pathophysiology of ATL and risk-adapted treatment approaches. Methods Reflecting these advances, ATL researchers and clinicians joined together at the 18th International Conference on Human Retrovirology—Human T-Lymphotropic Virus and Related Retroviruses—in Tokyo, Japan, March, 2017, to review evidence for current clinical practice and to update the consensus with a new focus on the subtype classification of cutaneous ATL, CNS lesions in aggressive ATL, management of elderly or transplantation-ineligible patients, and treatment strategies that incorporate up-front allogeneic hematopoietic stem-cell transplantation and novel agents. Results As a result of lower-quality clinical evidence, a best practice approach was adopted and consensus statements agreed on by coauthors (> 90% agreement). Conclusion This expert consensus highlights the need for additional clinical trials to develop novel standard therapies for the treatment of ATL

Among the 138 adult patients with ALCL, 64 (46%) were ALK positive, and 74 (54%) were ALK negative. Median follow-up was 8 years. At diagnosis, significantly more patients younger than 40 years old were ALK positive than ALK negative (66% v 23%, respectively; P < .001). Comparing patients with ALK-positive and ALK-negative ALCL, β(2)-microglobulin was ≥ 3 mg/L in 12% and 33% (P = .017); International Prognostic Index was high (score, 3 to 5) in 23% and 48% (P = .03); complete response rates to first-line treatment were 86% and 68% (P = .01); and 8-year overall survival (OS) rates were 82% (95% CI, 69% to 89%) and 49% (95% CI, 37% to 61%), respectively (P < .001). The survival difference mostly affected patients age ≥ 40 years. Multivariate analysis identified β(2)-microglobulin ≥ 3 mg/L (P < .001) and age ≥ 40 years (P = .029), but not ALK status, as prognostic for OS. These two variables distinguished four survival risk groups, with 8-year OS ranging from 84% to 22%. CONCLUSION Results of this long-term study enabled refinement of the prognosis of adult systemic ALCL, with ALK prognostic value dependent on age, and could provide guidance for eventual treatment adjustment.

Since its identification, 75 years ago, the monoamine serotonin (5-HT) has attracted considerable attention toward its role as a neurotransmitter in the central nervous system. Yet, increasing evidence, from a growing number of research groups, substantiates the fact that 5-HT regulates important nonneuronal functions. Peripheral 5-HT, synthesized by the enzyme tryptophan hydroxyase (Tph) in intestinal cells, was assumed to be distributed throughout the entire body by blood platelets and to behave as a pleiotropic hormone. A decade ago, generation of a mouse model devoid of peripheral 5-HT lead to the discovery of a second isoform of the enzyme Tph and also suggested that 5-HT might act as a local regulator in various organs. The objective of this review is to highlight the newly discovered functions played by the monoamine using the Tph1 KO murine model and to outline current findings that led to the discovery of complete serotonergic systems in unexpected organs. Within an organ, both the presence of local Tph enzymatic activity and serotonergic components are of particular importance as they support the view that 5-HT meets the criteria to be qualified as a monoamine with a paracrine/autocrine function.

on behalf of the ANRS HC-13 Lympho-C Study Group Hepatitis C virus (HCV) infection increases the risk of B-cell non-Hodgkin lymphomas (B-NHL). Antiviral treatment (AT) can induce hematological responses in patients with marginal zone lymphomas (MZL). The ANRS HC-13 Lympho-C study aimed at a better understanding of the impact of AT on HCV associated B-NHL. This multicentric study enrolled 116 HCV-positive patients with B-NHL between 2006 and 2012. Cytological and histological samples were collected for centralized review. At lymphoma diagnosis, median age was 61 years and gender ratio M/F was 1. Cytohistological distribution was marginal zone lymphoma (MZL) n 5 45 (39%), diffuse large B-cell lymphoma (DLBCL) n 5 45 (39%), and other types n 5 26 (22%). MZL patients had more frequent detection of rheumatoid factor (68% vs. 35%; P 5 0.001) and more frequently mixed cryoglobulinemia (74% vs. 44%; P 5 0.021) than patients with DLBCL. Among patients receiving AT, a sustained virologic response was achieved in 23 of 38 (61%) patients with MZL and in 9 of 17 (53%) with DLBCL (P 5 0.42). Three-year overall survival (OS) and progression-free survival were 78% 95%CI and 64% , respectively, without difference between cytohistological groups. Outcome analysis showed a favorable association between OS and AT in all patients (P 5 0.05) and in the subgroup of MZL patients only (P 5 0.04). Our data support that AT improves the outcomes of HCV-associated NHLs. The impact of new AT regimen with protease inhibitor needs to be investigated in this setting. [clinicalTrials.gov Identification number NCT01545544]Am.

Invariant natural killer T (iNKT) cells can experimentally dissociate GVL from graftversus-host-disease (GVHD). Their role in human conventional allogeneic hematopoietic stem cell transplantation (HSCT) is unknown. Here, we analyzed the post-HSCT recovery of iNKT cells in 71 adult allografted patients. Results were compared with conventional T-and NK-cell recovery and correlated to the occurrence of GVHD, relapse, and survival. We observed that posttransplantation iNKT cells, likely of donor origin, recovered independently of T and NK cells in the first 90 days after HSCT and reached greater levels in recipient younger than 45 years (P ‫؍‬ .003) and after a reducedintensity conditioning regimen (P ‫؍‬ .03). Low posttransplantation iNKT/T ratios (ie, < 10 ؊3 ) were an independent factor associated with the occurrence of acute GVHD (aGVHD; P ‫؍‬ .001). Inversely, reaching iNKT/T ratios > 10 ؊3 before day 90 was associated with reduced nonrelapse mortality (P ‫؍‬ .009) without increased risk of relapse and appeared as an independent predictive factor of an improved overall survival (P ‫؍‬ .028). Furthermore, an iNKT/T ratio on day 15 > 0.58 ؋ 10 ؊3 was associated with a 94% risk reduction of aGVHD. These findings provide a proof of concept that early postallogeneic HSCT iNKT cell recovery can predict the occurrence of aGVHD and an improved overall survival. (Blood. 2012;120(10):2144-2154)

ASCT is a feasible procedure in young patients with advanced WM. ASCT should not be offered to patients with chemoresistant disease and to those who received more than three lines of therapy.

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Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT.Methods: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed.Results: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. Conclusion(s):Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.