Quantification of Dendritic Cells and Osteoclasts in the Bone Marrow of Patients with Monoclonal Gammopathy

The purpose of this study was to find histological clues for reliable differentiation between monoclonal gammopathy of undetermined significance (MGUS) and myeloma when clinical parameters are controversial. Differential appearance of dendritic cells and osteoclasts, two cell types developing from the monocytic lineage upon distinct cytokine activation profile, might be a useful approach. Bone and bone-marrow biopsies performed in 105 patients were studied using histomorphometry after identification of osteoclasts (by histochemical identification of tartrate resistant acid phosphatase) and dendritic cells (by immunohistochemical detection of the S-100 protein). Patients were classified by the World Health Organization criteria but histopathological criteria were more adapted to identify MGUS (53 cases), myeloma (46), B-cell lymphoma (six) since six myeloma were not correctly classified. Histomorphometry was compared to 15 control cases. The number of marrow dendritic cell was significantly increased with B-cell lymphoma >MGUS >myeloma > controls. Dendritic cell were often mixed with lymphoma cells. Myeloma had increased bone resorption with a high osteoclast number and moderate increase in dendritic cells. B-cell lymphomas had a considerable increase in dendritic cell but presented mononucleated osteoclasts. These findings can help in the classification of MGUS in the early stages of the disease and could help to propose preventive treatments

Computed Microtomography of Bone Specimens for Rapid Analysis of Bone Changes Associated With Malignancy

Breast and prostate cancers are specially metastasizing to bone. Metastases from breast cancer usually exhibit a mixed osteolytic/osteosclerotic aspect, with osteolysis predominating. Osteosclerosis is a common finding in prostatic cancer although osteolysis occurs within the sclerotic lesions. B-cell malignancies (lymphoma, myeloma) are also associated with marked osteolysis. Histopathological examination of bone biopsies was used for the diagnosis of malignancies and, prior to embedding, microcomputed tomography (microCT) was done on the bone specimens. Patients (247) who presented either a bone metastasis, an overt myeloma, a lymphoma or a monoclonal gammopathy of undetermined significance were studied. All patients had a bone biopsy studied by 2D histomorphometry for the histopathology. During the fixation time, the bone cores were analyzed by microCT. On the 3D reconstructed models provided by microCT, signs of osteolysis/osteosclerosis were searched: excess of bone resorption, focal disorganization of microarchitecture, bone metaplasia, osteosclerosis. A strong agreement was obtained between histomorphometry and microCT results using Cohen\u27s kappa test (κ = 0.713). MicroCT identified excess bone resorption on trabecular surfaces when eroded surfaces were >10.5% by histomorphometry. MicroCT failed to identify some patients with smoldering myeloma or some lymphomas with microresorption. MicroCT data are obtained within 4 hr and suggest the malignant invasion of bone marrow when excess of bone resorption/formation is obtained. MicroCT can be used in the immediate postbiopsy period making possible a fast identification of malignancy. However these signs are not specific and must be confirmed by histopathological analysis

Apport diagnostique du dosage des chaînes légères libres sériques d'immunoglobulines pour l'exploration des gammapathies monoconales

RésuméLes gammapathies monoclonales sont d\u27occurrence non négligeable (3,2 %) chez les sujets de plus de 50 ans. Pour environ la moitié d\u27entre elles, elles correspondent, lors de leur découverte, à une gammapathie monoclonale de signification indéterminée (ou MGUS en anglais pour monoclonal gammopathy of undetermined significance). Un peu plus du tiers sont des hémopathies lymphoïdes B avérées (myélome multiple, maladie de Waldenström, amylose) qui représentent le stade ultime de progression des MGUS avec une incidence annuelle de 1 %. L\u27exploration biologique immunologique validée à ce jour repose sur une analyse conjointe du sérum et des urines par immunoélectrophorèse/immunofixation qui vise à typer l\u27immunoglobuline monoclonale. Depuis 2001, un nouveau dosage est proposé pour la prise en charge diagnostique de ces patients : la détermination néphélémétrique ou turbidimétrique des chaînes légères libres (CLL) d\u27immunoglobulines kappa et lambda à l\u27aide d\u27anti-sérums spécifiques avec détermination du rapport κ/λ dont le déséquilibre peut être indicateur d\u27un excès de production monoclonale. Cela reste cependant un dosage quantitatif qui ne peut faire la preuve d\u27une anomalie qualitative (monoclonalité). L\u27apport pour le diagnostic et pour le suivi de ce dosage doit tenir compte des propriétés de la réaction antigène/anticorps en milieu liquide (phénomène de zone), du métabolisme rénal des chaînes légères avec ses conséquences en cas d\u27insuffisance rénale et des interférences possibles avec les chaînes légères liées des immunoglobulines intactes. L\u27apport diagnostique du dosage des CLL est patent dans les situations cliniques où l\u27absence de marqueur monoclonal peut être un handicap : myélome à chaîne légère, myélome apparemment non sécrétant, amylose et maladie de dépôt des chaînes d\u27immunoglobulines. Dans les autres situations (myélome à immunoglobuline intacte, MGUS), l\u27apport du dosage des CLL comme marqueur diagnostique ou comme indicateur de pronostic ou de suivi thérapeutique n\u27est pas encore prouvé. Son évaluation nécessitera des études prospectives particulièrement rigoureuses

Systemic and immune manifestations in myelodysplasia: a multicenter retrospective study

OBJECTIVE: The presence of systemic and/or immune manifestations in myelodysplasia has been currently reported. The influence of these manifestations on the natural outcome of myelodysplastic syndrome has to be considered. We present a multicenter retrospective study (2002-2009) of patients with myelodysplastic syndrome disclosing systemic and/or immune manifestations. METHODS: Forty-six patients with myelodysplasia presenting with systemic and/or immune manifestations were compared in terms of survival with 189 patients with myelodysplasia lacking these features. RESULTS: The clinical picture in these cases consisted of fever (13%), arthralgia or arthritis (13%), and cutaneous manifestations (67%). Four cases of systemic vasculitis have been reported in our series, and they have a worse prognosis. Immune anomalies were recorded in 29% of the cases, and the presence of cryoglobulins was also associated with a worse prognosis. CONCLUSION: A difference in survival between patients with myelodysplastic syndrome with systemic manifestations and patients lacking these manifestations has been observed in the presence of systemic vasculitis and/or cryoglobulins

2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) can identify chronic lymphocytic leukaemia (CLL) stage A et stage B patients

Purpose: There is no data in the literature concerning the utility of 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in chronic lymphocytic leukaemia (CLL), except for the diagnosis of Richter\u27s transformations. The purpose of this study was to assess the potential role of FDG-PET in CLL stages A and B. Materials and methods: Thirty-five patients (61 ± 9 years; 11 women, 24 men; 8B and 27A) have benefited of a FDG-PET scan at baseline, for example, before an eventual treatment. FDG-PET scans were analyzed visually and the maximum values of the Standardised Uptake Value (SUVmax) were measured in the main lymph nodes areas. The ability of FDG-PET to differentiate stages A and B patients was evaluated by Student\u27s tests and Receiver Operating Characteristics (ROC) analysis. Results: All patients with a normal FDG-PET (n = 18) were stages A. The remaining 17 patients (9A and 8B) showed hypermetabolisms in nodal areas above (n = 17) and below (n = 9) the diaphragm, and no visceral involvement. The lymph nodes hypermetabolisms were always bilateral, and of low intensity (≤ mediastinum; 9A), or of higher intensity (≥ liver, 8B). The SUVmax of stage B (n = 8) were significantly higher than those of the 27 stages A, in all lymph nodes areas except in mediastinum. The highest intensity of FDG uptake was observed in axillary area in stages B patients (SUVmax = 2.74 ± 1.03). An axillary SUVmax of 1.33 is the most suitable value for the discrimination between stages A and B patients (ROC; AUC = 0.968; sensitivity 1.00; specificity 0.91). Conclusion: Lymph nodes hypermetabolisms are constant in the B stage, and more intense than in stage A. These anomalies are always bilateral, unlike what is observed in Richter\u27s transformation. The intensity of axillary lymph nodes FDG uptake can distinguish CLL stages A and B

Lymphome T cutané et systémique traité avec succès par greffe haplo-identique

BACKGROUND: Herein, we report a case of systemic cutaneous T-cell lymphoma refractory to standard therapy, the course of which resulted in haplo-identical bone marrow grafting. PATIENTS AND METHODS: A 53-year-old woman consulted for facial erythema with infiltration, keratotic lesions on the trunk, and adenopathies measuring around 1cm on the axilla and inguinal folds. A diagnosis was made of Sézary syndrome (SS), a leukaemic form of epidermotropic cutaneous T-cell lymphoma. After three years of treatment with methotrexate, the patient developed transformed SS with visceral involvement. Given the high risk of relapse and the absence of an HLA-compatible donor, haploidentical bone marrow grafting was performed. The patient was still in complete remission two and a half years later. The disease course was nevertheless marked by the emergence one year after grafting of a Blaschko-distributed lichenoid eruption having histological features consistent with chronic graft-versus-host disease (GVHD); treatment with topical betamethasone proved efficacious. DISCUSSION: To our knowledge, this is the first reported case of haploidentical grafting for systemic and transformed cutaneous T-cell lymphoma. This approach could henceforth represent a therapeutic option for patients requiring an allograft in the absence of compatible donors. The Blaschko-distributed lichenoid lesions attributed to chronic GVHD could be the result of reduced immune tolerance to abnormal embryological clones leading to a T-lymphocyte-mediated inflammatory reaction

Les immunothérapies spécifiques dans le traitement des cancers

The offer of anti-cancer drugs has recently been disrupted by the introduction of checkpoint inhibitors on the market. Currently, one anti-CTLA-4, two anti-PD-1 and two anti-PD-L1 are authorized in the European Union, in seven different types of cancer. The clinical development of these therapies is still in full swing: in July 2017, more than 1 500 clinical trials were evaluating anti-PD-1, anti-PD-L1 and anti-CTLA-4 drugs in about twenty different locations and this number continues to increase. In the short term in France, other immunotherapies, the CAR-T cells, will complete this therapeutic arsenal. These immunotherapies appear as a real revolution in the treatment of some cancers. Nevertheless, many issues are associated with these therapies, particularly regarding the identification of good responders, the proper use of these drugs including the management of therapeutic strategies and safety profile, as well as the organization of care. In addition, the expenses associated with ipilimumab, nivolumab and pembrolizumab are substantial and almost tripled in one year, going from 120 million euros in 2015 to more than 340 million euros in 2016. This raises the question of the ability of the current healthcare system to maintain equitable access to innovation and best treatments for all patients. For all these reasons, the French National Cancer Institute decided to dedicate its thematic annual report on these innovative immunotherapies, targeting in particular checkpoint inhibitors and CAR-T cells, in order to produce an inventory of current data and an analysis regarding the different issues associated with these therapies

Antithrombotic effects of hydroxychloroquine in primary antiphospholipid syndrome patients

International audienc

Arterial stiffness and stroke in sickle cell disease

BACKGROUND AND PURPOSE: Large vessels are also affected in sickle cell disease. The aim of this study was to assess several parameters in adult patients with sickle cell disease compared with control subjects and in patients with sickle cell disease with stroke. METHODS: Carotid arterial stiffness, intima-media thickness, and transcranial Doppler ultrasonography were measured. RESULTS: Arterial stiffness and transcranial Doppler velocity were significantly increased in 49 patients with sickle cell disease compared with 47 control subjects (P<0.05) and especially in patients with stroke (P<0.05). CONCLUSIONS: These data suggest that transcranial Doppler and arterial stiffness might be associated to stroke in adult patients with sickle cell disease