82 research outputs found
Correction to: Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party (Bone Marrow Transplantation, (2021), 56, 3, (605-613), 10.1038/s41409-020-01069-w)
No full textThe Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party, written by Johannes Schetelig, Patrice Chevallier, Michel van Gelder, Jennifer Hoek, Olivier Hermine, Ronjon Chakraverty, Paul Browne, Noel Milpied, Michele Malagola, Gerard Socié, Julio Delgado, Eric Deconinck, Ghandi Damaj, Sebastian Maury, Dietrich Beelen, Stéphanie Nguyen Quoc, Paneesha Shankara, Arne Brecht, Jiri Mayer, Mathilde Hunault-Berger, Jörg Bittenbring, Catherine Thieblemont, Stéphane Lepretre, Henning Baldauf, Liesbeth C. de Wreede, Olivier Tournilhac, Ibrahim Yakoub-Agha, Nicolaus Kröger, Peter Dreger was originally published Online First without Open Access. After publication in volume 56, issue 3, page 605–613 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0. Open access funding enabled and organized by Projekt DEAL
Development of new tools to determine diagnosis and prognosis of patients with myeloproliferative neoplasms.
No full textPlusieurs scores pronostiques ont été élaboré chez les patients atteints de leucémie myéloïde chronique (LMC) sans qu’un lien n’ait été établi entre ces scores et la biologie de la LMC. Nous montrons que les patients de mauvais pronostic ont une expression accrue de GATA2, en corrélation avec les taux de basophiles et de plaquettes au diagnostic, paramètres utilisés dans le calcul des scores pronostiques, et à l’expression de gènes impliqués dans le fonctionnement des basophiles. Cette expression augmente lors de la transformation sur un versant myéloïde. Alors qu’un certain nombre de patients peuvent désormais tenter un arrêt de traitement avec un succès dans 50% des cas, il apparaît essentiel de revoir notre manière d’évaluer le pronostic. Ainsi, l’obtention d’une réponse moléculaire optimale dès 6 mois est associée avec une tentative ultérieure d’arrêt de traitement dans notre cohorte. Alors que le diagnostic de la LMC est relativement aisé, il est parfois difficile de différencier thrombocytémie essentielle (TE), pré-myélofibrose et myélofibrose. Nous réévaluons l’intérêt de la numération des cellules CD34+ circulantes: un nombre de cellules CD34+ circulantes < 10/μl permet d’exclure le diagnostic de myélofibrose avec une très bonne sensibilité (97%) et spécificité (90%). Dans une cohorte de patients atteints de TE avec mutation CALR, nous montrons que l’augmentation de sa charge allélique, et non la présence de mutations additionnelles, est associée à un risque accru de progression. L’ensemble de ces paramètres sera étudié dans une étude prospective multicentrique visant à établir un score diagnostique non invasif permettant de différencier TE, pré-myélofibrose et myélofibrose.Various scoring systems have been successively elaborated to predict outcome of patients with chronic myeloid leukemia (CML). However, no link has been identified between those scores and CML biology. We show that high-risk patients have high GATA2 levels, in correlation with higher baseline basophil and platelet counts, two parameters used to calculate prognostic scores, and expression of genes involved in basophils. GATA2 expression increases in accelerated and myeloidblast-phase. Since some patients can now stop treatment, with a near 50% success rate, it is necessary to reevaluate the way we assess prognosis. A 6-month optimal molecular response was associated with an increased discontinuation attempt rate in our cohort. While the diagnosis of CML is fairly easy, it is often difficult to distinguish essential thrombocythemia (ET), pre-myelofibrosis and myelofibrosis. The numeration of CD34+ circulating cells is of interest in this setting : we show that a number < 10/μ excludes the diagnosis of myelofibrosis with a very good sensitivity (97%) and good specificity (90%). In a cohort of patients with ET and CALR mutation, We show that an increase in allele burden, and not additional mutations at diagnosis or during follow-up,is associated with an increased risk of progression. All of these parameters will be evaluated in a prospective multicentric study in order to elaborate a non-invasive diagnostic score to distinguish TE, pre-myélofibrosis, and myelofibrosis
A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS
No full textErythropoiesis-stimulating agents are first choice for treating anemia in low-risk MDS. This double-blind, placebo-controlled study assessed the efficacy and safety of epoetin-α in IPSS low- or intermediate-1 risk (i.e., low-risk) MDS patients with Hb ≤ 10.0 g/dL, with no or moderate RBC transfusion dependence (≤4 RBC units/8 weeks). Patients were randomized, 2:1, to receive epoetin-α 450 IU/kg/week or placebo for 24 weeks, followed by treatment extension in responders. The primary endpoint was erythroid response (ER) through Week 24. Dose adjustments were driven by weekly Hb-levels and included increases, and dose reductions/discontinuation if Hb > 12 g/dL. An independent Response Review Committee (RRC) blindly reviewed all responses, applying IWG-2006 criteria but also considering dose adjustments, drug interruptions and longer periods of observation. A total of 130 patients were randomized (85 to epoetin-α and 45 to placebo). The ER by IWG-2006 criteria was 31.8% for epoetin-α vs 4.4% for placebo (p < 0.001); after RRC review, the ER was 45.9 vs 4.4% (p < 0.001), respectively. Epoetin-α reduced RBC transfusions and increased the time-to-first-transfusion compared with placebo. Thus, epoetin-α significantly improved anemia outcomes in low-risk MDS. IWG-2006 criteria for ER may require amendments to better apply to clinical studies
Absence de valeur diagnostique ou pronostique de l'expression du CD36, du nombre de plaquettes réticulées ou de microparticules plaquettaires évalués par cytométrie de flux au cours des thrombocytémies essentielles et des thrombocytoses réactionnelles
No full textANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
Increased apoptosis in mononucleated cells but not in CD34+ cells in blastic forms of myelodysplastic syndromes
No full textLymphomatoid Granulomatosis and Tuberculosis, Coincidence or Cohabitation—A Case Report
No full textBackground: Lymphomatoid granulomatosis (LYG) is a rare and atypical EBV-induced B-cell lymphoproliferative disorder. Clinical manifestations are mainly respiratory, with nodular infiltrates, varying in number and size, being responsible for respiratory distress. Cutaneous, hepatic, or neurological involvement is also possible. Although pathogenesis is not clearly elucidated, quantitative or qualitative cellular immunodepression is thought to be a main factor. Here, we report a case of concomitant LYG and pulmonary tuberculosis. Case presentation: An 80-year-old female patient presented to the emergency unit for steadily increasing dyspnea, with workup revealing bilateral pulmonary nodules and mediastinal lymph node enlargement on chest imaging. Empiric antibiotic therapy was initially started with amoxicillin-clavulanate, which was later combined with azithromycin following respiratory deterioration. A CT-guided lung biopsy showed grade 2 LYG. Treatment with corticosteroids and weekly rituximab was initiated, leading to rapid improvement of respiratory symptoms. After the second dose of rituximab, sputum cultures that were initially collected were found to be positive for Mycobacterium tuberculosis. Rituximab was suspended, and antituberculous treatment was initiated. Rituximab was restarted once tuberculosis was controlled. Follow-up imaging later showed adequate control of both tuberculosis and LYG, with at least a partial remission of the latter. Conclusions: Our case highlights the importance of a complete diagnostic workup when a diagnosis of LYG is made, to avoid missing a concomitant pulmonary disease, such as tuberculosis, even when definite pathologic and clinical features of the former are present
TP53 Mutation Status Divides Myelodysplastic Syndromes with Complex Karyotypes into Distinct Prognostic Subgroups
No full textOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at https://www.nature.com/articles/s41375-018-0351-2.pdfRisk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p 10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features.We would like to thank the MDS Foundation for their support of the International Working Group for MDS and Celgene for funding the efforts of the IWG-prognosis molecular subcommittee and this study. RB was additionally supported by K08 DK091360. PV acknowledges funding from the MRC Disease Team Awards (G1000729/94931 and MR/L008963/1) MRC Molecular Haematology Unit and the Oxford Partnership Comprehensive Biomedical Research Centre (NIHR BRC Funding scheme. oxfbrc-2012-1). LQ is funded by an MRC Clinician Scientist Fellowship. JB and AP acknowledge funding from Bloodwise (UK). LM acknowledges funding from Associazione Italiana per la Ricerca sul Cancro (AIRC, Individual Grant 20125). MH acknowledges funding from DFG grant HE 5240/6-1. In addition, we would like to thank the following for their help with this study: Jin Shao from Washington University in St. Louis, USA; Professor Mathilde Hunault-Berger from CHU Angers, France; Professor Norbert Vey from Institut Paoli Calmettes, Marseille, France; Michael Byrne, P Brent Ferrell, David R Head, Ridas Juskevicius, Carrie Kitko, Emily F Mason, Sanjay R Mohan, Claudio A Mosse, Tamara K Moyo, Aaron C Shaver, Andrew L Sochacki, and Stephen A Strickland from Vanderbilt University
JAK inhibition for CD3− CD4+ lymphocytic-variant hypereosinophilic syndrome
No full textInternational audienceAlternatives are urgently needed in patients with CD3- CD4+ lymphocytic-variant hypereosinophilic syndrome (L-HES) requiring high-level steroids or who are unresponsive and/or intolerant to conventional alternative therapies. We report five L-HES patients (44-66 years) with cutaneous involvement (n = 5) and persistent eosinophilia (n = 3) despite conventional therapies, who successfully received JAK inhibitors (tofacitinib n = 1, ruxolitinib n = 4). JAKi led to complete clinical remission in the first 3 months in all (with prednisone withdrawal in four). Absolute eosinophil counts normalized in cases receiving ruxolitinib, while reduction was partial under tofacitinib. After switch from tofacitinib to ruxolitinib, complete clinical response persisted despite prednisone withdrawal. The clone size remained stable in all patients. After 3-13 months of follow-up, no adverse event was reported. Randomized controlled trials are now mandatory to optimize the use of JAKi in L-HES
Progressive multifocal leukoencephalopathy after durvalumab treatment for acute myeloid leukemia: A consequence of an immune reconstitution inflammatory syndrome?
No full textProgressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system resulting from the reactivation of the John Cunningham virus (JCV). PML occurs almost exclusively during profound immune suppression but it can also be observed in immunocompromised subjects as part of an inflammatory immune reconstitution syndrome (IRIS) in patients receiving antiviral therapy. We report a case of PML in a 61‐year‐old patient with acute myeloid leukemia who had developed after discontinuation of durvalumab (anti‐PD‐L1) therapy initiated after multiple treatments. Results suggest that PML may result from two nonexclusive mechanisms: (i) an inhibition of the protective response of JCV‐specific T cells as a consequence of the blockade of the PD1‐PDL1 pathway, associated with a lack of compensatory expression of other inhibitory receptors by T cells and (ii) a neuroinflammatory response (PML‐IRIS) that may have contributed to virus reactivation
Thromboembolism prophylaxis in adult patients with acute lymphoblastic leukemia treated in the GRAALL-2005 study.
No full textPatients undergoing treatment of acute lymphoblastic leukemia (ALL) are at risk for thrombosis, caused in part by the use of l-asparaginase (L-ASP). Antithrombin (AT) replacement has been suggested to prevent venous thromboembolism (VTE) and thus may increase exposure to ASP. We report herein the results of the prophylactic replacement strategy in the pediatrics-inspired prospective GRAALL-2005 study. Between 2006 and 2014, 784 adult patients with newly diagnosed Philadelphia- ALL were included. The incidence rate of VTE was 16%, with 69% of cases occurring during induction therapy. Most patients received AT supplementation (87%). After excluding patients who did not receive L-ASP or who developed thrombosis before L-ASP, AT supplementation did not have a significant impact on VTE. Administration of fibrinogen concentrates was associated with an increased risk of VTE, whereas transfusion of fresh frozen plasma had no effect. Heparin prophylaxis was associated with an increased risk of VTE. Prophylactic measures were not associated with an increased risk of grade 3 to 4 bleeding complications. The rate of VTE recurrence after L-ASP reintroduction was 3% (1 of 34). In ALL patients receiving L-ASP therapy, the use of fibrinogen concentrates may increase the risk of thrombosis and should be restricted to rare patients with hypofibrinogenemia-induced hemorrhage. VTE developed despite extensive AT supplementation, which suggests the need for additional prophylactic measures. Although this large descriptive study was not powered to demonstrate the efficacy of these prophylactic measures, it provides important insight to guide future trial design. This trial was registered at www.clinicaltrials.gov as #NCT00327678
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