High tumor burden before blinatumomab has a negative impact on the outcome of adult patients with B-cell precursor acute lymphoblastic leukemia. A real-world study by the GRAALL

Blinatumomab is a bispecific T-cell engager approved for B-cell precursor acute lymphoblastic leukemia (B-ALL) with persistent minimal residual disease (MRD) or in relapse. The prognostic impact of tumor load has been suggested before other immunotherapies but remains poorly explored before blinatumomab. We retrospectively analyzed the outcome of 73 patients who received blinatumomab either in first complete remission (CR) with MRD (n=35) or at relapse (n=38). Among MRD patients, 91% had MRD >0.01% before blinatumomab, and 89% achieved complete MRD response after blinatumomab. High pre-blinatumomab MRD levels were associated with shorter relapse-free survival (P=0.049) and overall survival (OS) (P=0.011). At 3 years, OS was 33%, 58% and 86% for pre-blinatumomab MRD >1%, between MRD 0.1- 1% and <0.1% respectively. Among relapsed patients, 23 received blinatumomab with overt relapse and 15 were in complete response (CR) after bridging chemotherapy. At 3 years, overall CR rate was 68% and complete MRD response rate was 84%. Patients who directly received blinatumomab had shorter relapse-free survival (P=0.033) and OS (P=0.003) than patients bridged to blinatumomab. Three-year OS was 66% in the latter group compared to 16% in the former group. Our observations suggest that pre-blinatumomab tumor burden should help to design more tailored strategies including tumor load reduction in relapsed patients

Integration of Immature Granulocytes Quantification With the Version 2.0 UniCel DxH 800 in the HematoFlow Strategy

International audienceOBJECTIVES: Our aim was to define whether the early granulocyte cell marker (EGC%_DxH) parameter might replace immature granulocytes counts obtained by HematoFlow (IG%_HF) and/or manual differential count (IG%\ₘanual). METHODS: We conducted a study over a 10-day period in February 2014 whereby 402 samples were analyzed for the IG flag. We correlated the EGC%_DxH vs IG%_HF and IG%\ₘanual, identified any discrepant results and finally looked at the impact on our workflow by incorporation of the EGC% into our WBC differential algorithm. RESULTS: On an initial training set, a receiver operating characteristic (ROC) curve analysis showed a threshold of 0.9% for EGC%_DxH (sensitivity of 91.7%, specificity of 93.5% and an area under the curve of 0.965). Further analysis of the dataset (259 samples) found a correlation of the EGC%_DxH to all our IG% counting methods (r = 0.963). Incorporation of the EGC%_DxH into the WBC HematoFlow differential resulted in a 36% reduction of samples requiring HematoFlow and/or slide review. CONCLUSIONS: The EGC% generated by the DxH 800 can be easily incorporated into existing HematoFlow and slide review algorithms

NK subtype of Large Granular Leukemia

International audienceLes leucémies à grands lymphocytes granuleux (LGL) sont des syndromes lymphoprolifératifs rares caractérisés par une expansion clonale de lymphocytes T ou natural killer (NK) dans 85 et 15 % des cas, respectivement. De manière intéressante, les leucémies LGL-T et -NK ont une physiopathologie commune et des présentations clinique et biologique similaires. Ce syndrome lymphoprolifératif est caractérisé par des cytopénies et une association fréquente à des maladies ou à des manifestations auto-immunes. Il s’agit d’une pathologie d’évolution indolente permettant, dans la plupart des cas, d’opter pour une stratégie d’abstention-surveillance au diagnostic. Néanmoins, la majorité des patients requerront l’initiation d’un traitement au cours du suivi. Les cellules NK étant dépourvues de récepteur des lymphocytes T (TCR), l’obtention d’une preuve de clonalité dans les leucémies à LGL-NK est difficile. Ce point est crucial, compte tenu de possibles expansions réactionnelles dans des contextes d’infections virales ou de pathologies dysimmunitaires. La démarche diagnostique a été facilitée par les progrès réalisés ces dernières années dans la compréhension de la physiopathologie et l’identification récente de mutations récurrentes. Dans cette revue, nous aborderons la physiopathologie des leucémies LGL-NK, nous présenterons les récents progrès réalisés dans les stratégies diagnostiques avant d’aborder la prise en charge thérapeutique

A reduced panel of eight genes (ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53) as an estimator of the tumor mutational burden in chronic lymphocytic leukemia

International audienceIntroduction: Mutational complexity or tumor mutational burden (TMB) influences the course of chronic lymphocytic leukemia (CLL). However, this information is not routinely used because TMB is usually obtained from whole genome or exome, or from large gene panel high‐throughput sequencing.Methods: Here, we used the C‐Harrel concordance index to determine the minimum panel of genes for which mutations predict treatment‐free survival (TFS) as well as large resequencing panels.Results: An eight gene estimator was defined encompassing ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53. TMB estimated from either a large panel of genes or the eight gene estimator was increased in treated patients or in those with a short TFS (6 months). Strikingly, the eight gene estimator was also highly informative for patients with Binet stage A CLL or with a good prognosis karyotype.Conclusion: These results suggest that the eight gene estimator, that is easily achievable by high‐throughput resequencing, brings robust and valuable information that predicts evolution of untreated patients at diagnosis better than any other parameter

Reference Values for WBC Differential by Hematoflow Analysis

International audienceObjectives - WBC differentials performed using flow cytometry with monoclonal antibodies have been developed in the last decade and are nowadays integrated into the routine workflow of some laboratories. Definition of reference values for each population is required in order to achieve an automatic validation of the results by laboratory software. Methods - We analyzed 584 samples from three hospitals using the Hematoflow solution to define the reference values. Results - Reference values are presented for five groups according to age (0-5, 6-11, 12-19, 20-69, and >69 years). Conclusions - These normal values will be helpful in the definition of relevant threshold for the automatic validation of samples analyzed by flow cytometry and the flagging of pathologic samples

Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome in the intensive care unit: a case report

International audienceBackgroundVacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome is a newly discovered inflammatory disease affecting male subjects, for which few data exist in the literature. Here, we describe the case of a patient with known Sweet's syndrome admitted to the intensive care unit and for whom a vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome was diagnosed, allowing for appropriate treatment and the patient's discharge and recovery.Case presentationA 70-year-old male White patient was hospitalized in the intensive care unit following an intrahospital cardiac arrest. History started a year before with repeated deep vein thrombosis and episodes of skin eruption compatible with Sweet's syndrome. After a course of oral steroids, fever and inflammatory syndrome relapsed with onset of polychondritis, episcleritis along with neurological symptoms and pulmonary infiltrates. Intrahospital hypoxic cardiac arrest happened during patient's new investigations, and he was admitted in a critical state. During the intensive care unit stay, he presented with livedoid skin lesions on both feet. Vasculitis was not proven; however, cryoglobulinemia screening came back positive. Onset of pancytopenia was explored with a myelogram aspirate. It showed signs of dysmyelopoiesis and vacuoles in erythroid and myeloid precursors. Of note, new deep vein thrombosis developed, despite being treated with heparin leading to the diagnosis of heparin-induced thrombocytopenia. The course of symptoms were overlapping multiple entities, and so a multidisciplinary team discussion was implemented. Screening for UBA1-mutation in the blood came back positive, confirming the vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome. Corticosteroids and anti-IL1 infusion were started with satisfactory results supporting patient's discharge from intensive care unit to the internal medicine ward.ConclusionsVacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome should be suspected in male patients presenting with inflammatory symptoms, such as fever, skin eruption, chondritis, venous thromboembolism, and vacuoles in bone marrow precursors. Patients with undiagnosed vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome may present with organ failure requiring hospitalization in intensive care unit, where screening for UBA1 mutation should be performed when medical history is evocative. Multidisciplinary team involvement is highly recommended for patient management, notably to start appropriate immunosuppressive treatments

Alien Registration- Smith, John (Eustis, Franklin County)

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Pan-HDAC Inhibitors May Restore PRDM1 Expression in Follicular Lymphoma

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Molecular mechanisms underlying transformation of large granular lymphocytic leukemia to high-grade T-cell lymphoma

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