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Hodgkin’s lymphoma (HL) is a hematological neoplasm generally related to a favorable prognosis, since approximately 80% of patients will be cured with actual regimen treatment. However, 10 to 30% o...

The aims of this study were to characterize the incidence and outcomes of severe toxicities following the administration of high-dose methotrexate (HD-MTX; ≥1 g/m2). Among the 468 patients included...

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy, for which conventional chemotherapy has poor outcomes. CD123, the α-subunit of interleukin (IL)-3 receptor, is constantly overexpressed at the surface of tumoral cells. Tagraxofusp (or SL-401) is a recombinant cytotoxin which consists of human interleukin-3 fused to a truncated diphtheria toxin. It is currently the only novel therapy with a prospective evaluation of efficacy and safety in the treatment of BPDCN and is also the only one to achieve FDA approval. In this short review, the results of tagraxofusp are summarized and perspectives of its use in BPDCN and in other malignancies are discussed. The safety profile is also summarized, since capillary leak syndrome is the main toxic effect of the drug, along with more common toxicities including an increase in transaminases and thrombocytopenia.

The introduction of purine nucleoside analogs, later in combination with alkylating moieties and anti-CD20 immunotherapy, has profoundly improved the response rate and response duration in patients with chronic lymphocytic leukemia (CLL). The quality of clinical response following treatment may be improved to a level where residual leukemic cells become undetectable. As patients with this type of response appear to have extended survival rates, minimal residual disease (MRD) eradication is considered a new objective in CLL treatment with the aim of improving progression-free survival (PFS) and potentially overall survival (OS). This review therefore aims to overview the prognostic value of MRD eradication in CLL, the role of post-remission intervention with "passive" immunotherapy (alemtuzumab or rituximab) so as to eliminate persistent MRD or prevent MRD relapse, the impact of these strategies on disease-free survival and their possible adverse consequences. The data indicate a potential for post-remission alemtuzumab or rituximab to prolong PFS in CLL, although more investigations and longer follow-up are required before MRD-guided strategies can be recommended outside of clinical trials.

Here, we examined both genetic and phenotypic determinants of nurse-like cells (NLCs) to better predict their putative functions in chronic lymphocytic leukemia (CLL). We showed that NLCs belong to the wound-healing macrophage subset (so-called 'M2 subset'), but most of all, unsupervised clustering analysis positions NLCs as CLL-specific tumor associated macrophages (TAMs). Chemokinome assays confirmed that NLCs secrete prototypical M2 cytokines and chemokines. Extending previous reports of fludarabine resistance, NLCs are able to promote multidrug resistance. Altogether, we propose that NLCs are not just nursing, but actively participate in the setting of an environment-mediated drug resistance (EM-DR) and immune escape for CLL cells.

Upregulation of T cell immunoglobulin-3 (TIM-3) has been associated with negative regulation of the immune response in chronic infection and cancer, including lymphoma. Here, we investigated the possible correlation between TIM-3 expression by ex vivo cytotoxic T cells (CTL) from follicular lymphoma (FL) biopsies and their functional unresponsiveness that could limit the favorable impact of CTL on disease progression. We report a high percentage of CD8+TIM-3+T cells in lymph nodes of FL patients. When compared to their CD8+TIM-3- counterparts, CD8+TIM-3+ T cells exhibited defective cytokine production following TCR engagement. Furthermore, CD8+TIM-3+ T cells display ex vivo markers of lytic granule release and remain unresponsive to further TCR-induced activation of the lytic machinery. Although confocal microscopy showed that TIM-3 expression on CD8+ T cells correlated with minor alterations of immunological synapse, a selective reduction of ERK signaling in CD8+TIM-3+T cells was observed by phospho-flow analysis. Finally, short relapse-free survival despite rituximab(R)-chemotherapy was observed in patients with high content of TIM-3+ cells and a poor infiltrate of granzyme B+ T cells in FL lymph nodes. Together, our data indicate that, besides selective TCR early signaling defects, TIM-3 expression correlates with unresponsiveness of ex vivo CD8+ T cells in FL. They show that scores based on the combination of exhaustion and cytolytic markers in FL microenvironment might be instrumental to identify patients at early risk of relapses following R-chemotherapy.