Painful ophthalmoplegia in a patient with a history of marginal zone lymphoma.

A 73-year-old man with a history of marginal zone lymphoma was admitted to the emergency room for diplopia and ipsilateral headache. The Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) demonstrated intense and symmetrical hypermetabolism of the cavernous sinuses, and hypermetabolic lesions diffusely in the lymph nodes and bones. The diagnosis of high-grade relapse of lymphomatous disease was made. In this context, the homogenous and symmetric lesion of the cavernous sinuses, without any other encephalic or meningeal lesions, raised the hypothesis of a paraneoplastic origin. A plausible paraneoplastic link between the neuro-ophthalmological lesion and the malignant disorder is IgG4-related disease, a condition that may be associated with lymphoma. As in our case, this diagnosis is often presumptive because histopathological confirmation is difficult to obtain.

[Management of thrombocytopenia]. / Mise au point d'une thrombopénie.

Thrombocytopenia is defined by a platelet level below 150 G/l. However, the limit of 100 G/l seems more appropriate to determine which thrombocytopenia will require further investigation. Initially, a thorough medical history should be performed as well as screening for any signs of bleeding. After having excluded the presence of platelet aggregates, it should be determined whether thrombocytopenia is isolated or associated with other abnormalities (cytopenias, coagulation disorder, abnormal renal or liver tests). Causes of thrombocytopenia along with the biological tests to achieve diagnosis, will be detailed in this article. We will then determine the medical emergencies that will need to be addressed to a reference center : active bleeding, biological signs of disseminated intravascular coagulation, acute renal failure, platelet count < 30 G/l (or < 50 G/l if the patient is on anticoagulation or antiplatelet therapy), significant and/or brutal onset pancytopenia. Outside these situations where vital prognosis is engaged, the patient should be rapidly addressed in case of platelet count between 30 and 50 G/l without any concomitant anticoagulation or antiplatelet therapy. Platelet levels between 50 and 100 G/l will require investigation, without any urgency, in outpatient haematology clinic.

La thrombopénie est définie par un taux de plaquettes inférieur à 150 G/l. Néanmoins, la limite de 100 G/l est plus appropriée pour déterminer les thrombopénies qui nécessitent une mise au point. Dans un premier temps, une anamnèse méticuleuse ainsi que la recherche de tout signe hémorragique devront être effectuées. Après avoir exclu la présence d'agrégats plaquettaires, il conviendra de déterminer si la thrombopénie est isolée ou associée à d'autres anomalies (cytopénies, troubles de la coagulation, altération des tests hépatiques ou de la fonction rénale). Les causes de thrombopénie, ainsi que les examens biologiques à réaliser afin de parvenir au diagnostic, seront détaillées dans notre article. Ensuite, nous déterminerons les situations d'urgences thérapeutiques, nécessitant d'adresser le patient en urgence dans un centre de référence: la présence de saignements actifs, de signes biologiques de coagulation intravasculaire disséminée, une insuffisance rénale aiguë, un taux de plaquettes < 30 G/l (ou < 50 G/l si le patient est traité par anticoagulant ou antiagrégant), une pancytopénie profonde et/ou d'apparition brutale. En dehors de ces situations à risque vital, il conviendra de référer rapidement le patient en cas de thrombopénie isolée entre 30 et 50 G/l, en dehors de tout traitement anticoagulant ou antiagrégant. Un taux de plaquettes entre 50 et 100 G/l nécessitera une mise au point sans urgence en consultation d'hématologie.

[Lymphomas: A therapeutic update]. / Actualités thérapeutiques dans les lymphomes.

Emergence of new molecules has considerably reshaped the management of patients in onco-hematology. Cytotoxic chemotherapy has not been altered, and CHOP remains the reference treatment for lymphomas. However, the development of targeted therapies has allowed for a broader spectrum of treatments. Immunotherapy with monoclonal antibodies entered the market with rituximab in diffuse large B-cell lymphomas, in the 1990s and it is now developing as new-generation anti-CD20 antibodies (obinotuzumab and ofatumumab). Anti-CD30 antibodies have been proposed in the treatment of T lymphomas and Hodgkin lymphomas. More recently, anti-PD1 antibodies have brought new perspectives in several cancers and more specifically in Hodgkin's lymphoma. Finally the BTK inhibitor, ibrutinib developed in the LLC has established itself in the management of mantle cell lymphoma and Waldenström macroglobulinemia. How can we deal with all these new molecules? Should they be offered as monotherapy or in association? In first line or relapse? The objective of this review is to trace history of the latest advances, and to highlight the validated strategies representing the new standards of treatment of lymphomas in 2017.

Azacytidine and erlotinib exert synergistic effects against acute myeloid leukemia.

The term myelodysplastic syndrome (MDS) identifies a heterogeneous group of clonal disorders originating from bone marrow stem cells that often progress to acute myeloid leukemia (AML). The reference treatments for MDS include the DNA methyltransferase inhibitors azacytidine and decitabine. Recently, the epidermal growth factor receptor (EGFR) inhibitor erlotinib has been shown to exert antileukemic activity in vitro and in vivo, independent of the EGFR. Thanks to this feature, erlotinib is currently being tested as an antileukemic drug in clinical trials. Here, we report that azacytidine and erlotinib mediate synergistic antineoplastic effects in several primary or secondary (post-MDS) AML cell lines. The combination of azacytidine and erlotinib blocked cell-cycle progression and induced caspase-dependent apoptosis more consistently than either of the two agents alone. These effects were not a consequence of cellular differentiation and could be discriminated from each other, as the former depended on caspases whereas the latter did not. The synergy between azacitidine and erlotinib, which involved the proteasomal degradation of the anti-apoptotic Bcl-2 family members MCL-1 and BCL2L10 and the upregulation of their pro-apoptotic counterpart PUMA, was abolished when azacytidine was replaced by decitabine but persisted when erlotinib was substituted with gefitinib, another EGFR inhibitor. Of note, the intracellular accumulation of azacytidine was exacerbated by both erlotinib and gefitinib, pointing to a pharmacokinetic mechanism of synergy. In approximately half of the cases studied, marrow and circulating blasts from MDS and AML patients, respectively, exhibited hyperadditive cytotoxic responses to the combination of azacytidine and erlotinib. These results strongly suggest that the combination of azacytidine and erlotinib may exert clinically relevant antileukemic effects.