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1.
Haematologica ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33626866

RESUMO

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20 % of cases. Among them, immune thrombocytopenia (ITP) has been reported but large studies assessing this association are missing. Whether such patients have a particular phenotype and require particular management is unclear. This study analyzes the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison (i) to patients with primary ITP without MDS/CMML and (ii) to patients with MDS/CMML without ITP. Forty-one MDS/CMML-associated ITP patients were included, with chronic ITP in 26 (63%) patients, low-risk myelodysplasia in 30 (73%) patients and CMML in 24 (59%) patients. An associated autoimmune disease was noted in 10 (24%) patients. In comparison to primary ITP patients, MDS/CMML-associated ITP patients had a higher occurrence of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulin (IVIg) (56%). Response achievement with IVIg was more frequent in primary ITP than in MDS/CMML-associated ITP patients. Response rates to second-line therapies were not statistically different between primary ITP and MDS/CMMLassociated ITP patients. Ten percent (n=4) of patients with MDS/CMML-associated ITP had multirefractory ITP versus none in primary ITP controls. After a median follow-up of 60 months, there was no difference in overall survival between MDS/CMML-associated ITP and primary ITP patients. Leukemia-free-survival was significantly better in MDS/CMMLassociated ITP patients than in MDS/CMML without ITP MDS/CMML-associated ITP have a particular outcome with more severe bleeding and multirefractory profile than primary ITP, similar response profile to primary ITP therapy except for IVIg, and less progression toward acute myeloid leukemia than MDS/CMML without ITP.

3.
Expert Rev Hematol ; : 1-14, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33249935

RESUMO

Introduction: Three distinct phases are recognized in immune thrombocytopenia (ITP): newly diagnosed (≤3 months after diagnosis), persistent (>3-12 months after diagnosis), and chronic (>12 months). Several international guidelines/expert recommendations have been released in the past 2 years regarding the treatment of newly diagnosed/persistent ITP. Areas covered: Across the guidelines/expert recommendations, thrombopoietin receptor agonists (TPO-RAs), including romiplostim (the focus of this review), are recommended in newly diagnosed or persistent ITP for patients who fail to respond to corticosteroids or intravenous immunoglobulin (or where these are contraindicated). To identify data relating to romiplostim in adults with newly diagnosed or persistent ITP, we conducted a search of PubMed (with no time limit applied) and abstracts from 2019 EHA/ASH meetings using the term 'romiplostim.' Expert opinion: The findings from nine clinical trials, six real-world studies and ten case reports provide insight into the early use of romiplostim, which could help to reduce exposure to the adverse effects associated with prolonged corticosteroid use, as well as reduce the risk of severe bleeding. Additionally, given the durable responses observed in patients with newly diagnosed/persistent ITP, as well as the potential for treatment-free responses following discontinuation, romiplostim might help to avoid the need for subsequent treatment.

4.
J Clin Med ; 9(11)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33228148

RESUMO

Acute chest syndrome (ACS) is a major complication of sickle-cell disease. Bacterial infection is one cause of ACS, so current guidelines recommend the routine use of antibiotics. We performed a prospective before-after study in medical wards and an intensive-care unit (ICU). During the control phase, clinicians were blinded to procalcitonin concentration results. We built an algorithm using the obtained measurements to hasten antibiotic cessation after three days of treatment if bacterial infection was not documented, and procalcitonin concentrations were all <0.5 µg/L. During the intervention period, the procalcitonin algorithm was suggested to physicians as a guide for antibiotic therapy. The primary endpoint was the number of days alive without antibiotics at Day 21. One-hundred patients were analyzed (103 ACS episodes, 60 in intervention phase). Possible or proven lung infection was diagnosed during 13% of all ACS episodes. The number of days alive without antibiotics at Day 21 was higher during the intervention phase: 15 [14-18] vs. 13 [13,14] days (p = 0.001). More patients had a short (≤3 days) antibiotic course during intervention phase: 31% vs 9% (p = 0.01). There was neither infection relapse nor pulmonary superinfection in the entire cohort. A procalcitonin-guided strategy to prescribe antibiotics in patients with ACS may reduce antibiotic exposure with no apparent adverse outcomes.

5.
Arthritis Rheumatol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001543

RESUMO

OBJECTIVE: To describe the efficacy and safety of biologics use for eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We conducted a retrospective European collaborative study including EGPA patients who received biologics for refractory and/or relapsing disease. RESULTS: Among 147 patients included, 63 received rituximab (RTX), 51 mepolizumab (MEPO) and 33 omalizumab (OMA). At inclusion, median (IQR) BVAS in the RTX, OMA and MEPO recipients were 8.5 (5-13), 2 (1-4.5) and 2 (1-5). In the RTX group, median BVAS fell to 1 (0-4.5) at 6 and 0 (0-2) at 12 months. Remissions, partial responses, failure and stop for adverse event were noted in 49%, 24%, 24% and 3%. For glucocorticoid (GC)-dependent asthma, MEPO had a much better GC-sparing effect and overall response than OMA. Remissions, partial responses, failure and stop for adverse event were noted in 15%, 33%, 48% and 4% for OMA, and 78%, 10%, 8% and 4% for MEPO. Remission rates were 76% and 82% at 12 months with MEPO 100 mg and 300 mg, respectively. CONCLUSION: These results suggest that rituximab could be effective in EGPA vasculitis relapses. Mepolizumab is highly effective with a good safety profile in GC-dependent asthma. Our data suggest that 100 mg monthly could be an acceptable first-line dose in selected instances of EGPA recognizing though that this has not been compared to the validated dose of 300 mg monthly.

7.
Haematologica ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32817288

RESUMO

B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From results obtained in mouse models, we hypothesized that combining rituximab with sequential injections of belimumab could increase the rate of response at one year in patients with persistent or chronic ITP by preventing the emergence of these long-lived plasma cells. The study was a single-center, single arm, prospective phase 2b trial (RITUX-PLUS, NCT03154385) investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, two weeks apart, combined with five infusions of belimumab, 10 mg/kg at week 0 (W0)+2 days, W2+2 days, W4, W8 and W12 for adults with primary persistent or chronic ITP. The primary endpoint was the total number of patients achieving an overall response (complete response + response) at W52 according to a standard definition. In total, 15 non-splenectomized adults, nine (60%) with persistent IPT and six (40%) with chronic ITP, were included. No severe adverse event, infection, or severe hypogammaglobulinemia was observed. Thirteen patients achieved an initial overall response. At W52, 12 (80%) patients achieved an overall response, including ten (66.7%) with complete response. When compared with a cohort of patients receiving rituximab alone, the kinetics of B-cell repopulation appeared similar, but the number of circulating T follicular helper cells was significantly decreased with belimumab combination therapy. Combining rituximab and belimumab seems a promising strategy in ITP, with high efficacy and acceptable safety.

8.
Blood ; 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814348

RESUMO

Management of immune thrombocytopenia (ITP) during pregnancy can be challenging since treatment choices are limited. Thrombopoietin receptor agonists (Tpo-RAs), which likely cross the placenta, are not recommended during pregnancy. To better assess safety and efficacy of off-label use of Tpo-RA during pregnancy, a multicenter observational and retrospective study was set up. Results from 15 pregnant women with ITP (17 pregnancies and 18 neonates) treated with either eltrombopag (N=8) or romiplostim (n=7) during pregnancy, including 2 patients with secondary ITP, were analyzed. Median time of Tpo-RA exposure during pregnancy was 4.4 weeks [range: 1-39 weeks]; the indication for starting Tpo-RA was preparation for delivery in 10/17 (58%) pregnancies whereas 4 had chronic refractory symptomatic ITP and 3 were on eltrombopag when the pregnancy started. Regarding safety, neither thromboembolic events among mothers nor Tpo-RA-related fetal or neonatal complications were observed except for one case of neonatal thrombocytosis. Response to Tpo-RA was achieved in 77% of cases, mostly in combination (70% of responders) with concomitant ITP therapy. Based on these preliminary findings, temporary off-label use of a Tpo-RA for severe and/or refractory ITP during pregnancy seems safe for both mother and neonate and likely to be helpful especially prior to delivery.

10.
Rev Med Interne ; 2020 Jul 14.
Artigo em Francês | MEDLINE | ID: mdl-32680716

RESUMO

Rituximab has been used for immune thrombocytopenia (ITP) for almost 20 years and is now considered a valid off-label second-line treatment. About 60% to 70% of patients with ITP show initial response to rituximab, but in half of these patients, the disease will eventually relapse. Therefore, in 30% of patients with persistent or chronic ITP, one course of rituximab at 375 mg/m2/week for 4 weeks or 2 fixed 1000-mg rituximab infusions allows for a sustained response rate at 5 years. Unfortunately, to date, no robust predictor of long-term sustained response has been found to assist the physician in deciding to treat with rituximab on an individual basis, and the choice of rituximab or another second-line treatment must be individualized and shared with the patient. Retreatment with rituximab has been found efficient, with a similar or higher magnitude and duration of response in most patients. Rituximab is usually well tolerated, with mainly mild and easily manageable infusion-related adverse events. Severe infections are uncommon, including in the long-term, and occur in patients with at least another contributing factor in more than two thirds. Several issues remain to be resolved. Indeed, head-to-head comparisons with other and new treatments in ITP and robust predictors of long-term response are urgently needed to better determine the position of rituximab in the therapeutic armamentarium for adult ITP. Additionally, the place of combination therapies, maintenance therapy with rituximab and rituximab in newly-diagnosed ITP deserve additional studies.

11.
BMJ ; 369: m1844, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409486

RESUMO

OBJECTIVE: To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen. DESIGN: Comparative observational study using data collected from routine care. SETTING: Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020. PARTICIPANTS: 181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care. INTERVENTIONS: Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group). MAIN OUTCOME MEASURES: The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting. RESULTS: In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment. CONCLUSIONS: Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Adulto Jovem
14.
Clin Immunol ; 215: 108419, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32289463

RESUMO

INTRODUCTION: We conducted a retrospective multicenter cohort study of patients receiving Immunoglobulin replacement therapy (IgRT) for secondary immune deficiency (SID) during 2012. METHODS: Data were retrospectively collected from the first dose of Ig administered in 2012 to 1 year afterward in terms of the indication for IgRT, as well as efficacy and safety. RESULTS: In total, 16 hospitals participated in the study, and 368 patients were included. Indications for IgRT were non-Hodgkin lymphoma (82 [22.3%] patients), multiple myeloma (76 [20.7%]), chronic lymphocytic leukemia (64 [17.4%]) and other (79 [21.5%]). Only 89 (24.2%) patients received IgRT according to 2011 European Medical Agency (EMA) recommendations; 196 (53.3%) received prophylactic antibiotics and 262 (76.2%) had an IgG level < 4 g/L before IgRT initiation. CONCLUSION: In this study, whatever the criteria, only 24.2% of patients with SID who received IgRT met EMA recommendations, which suggests a misuse of IgRT in SID.

15.
Clin Rheumatol ; 39(9): 2707-2713, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32206974

RESUMO

OBJECTIVE: Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed. METHODS: All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015. RESULTS: The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study. CONCLUSION: This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.

16.
Platelets ; 31(3): 291-299, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31272259

RESUMO

Less than 40% of patients with newly diagnosed adult immune thrombocytopenia will show spontaneous recovery within 12 months. Therefore, second-line treatments are frequently used to maintain a hemostatic platelet count or at best to cure the disease, with as few adverse effects as possible. Nevertheless, we lack head-to-head comparison studies of the different available treatments. Moreover, physicians have no robust predictors of response to guide decision-making on an individual basis. Therefore, there is no consensus, and decisions when to treat and with which drug must be individualized and shared with the patient based on factors related to the patient and the available second-line treatments. The main treatments used, based on their good benefit-risk ratio, are splenectomy, rituximab, and thrombopoietin-receptor agonists, but their prescription should be avoided in some situations and can be limited due to cost or to health authorities' restrictions on funding the last two drugs. This review presents the various second-line treatments used in primary persistent or chronic immune thrombocytopenia in adults and discusses their prescription in general and specific situations.


Assuntos
Púrpura Trombocitopênica Idiopática/terapia , Animais , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Humanos , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/etiologia , Retratamento , Resultado do Tratamento
17.
Regen Med Res ; 7: 2, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31821145

RESUMO

INTRODUCTION: Chronic, non-healing ulcers remain one of the most challenging clinical situations for health care practitioners. Often, conventional treatments fail and lead to amputation, further decreasing the patient's quality of life and resulting in enormous medical expenditures for healthcare systems. Here we evaluated the use of and cost-effectiveness of the RGTA (ReGeneraTing Agents) medical device CACIPLIQ20 (OTR4120) for chronic lower-extremity ulcers in patients with Leriche and Fontaine Stage IV peripheral arterial disease who were not eligible for revascularization. METHODS: This uncontrolled pilot study included 14 chronic lower extremity ulcers in 12 patients in one hospital. The pilot study included 12 patients with TcPO2 < 20 mm Hg and ABPI < 0.5 who had either a minimum of one chronic lower extremity ulcer or a chronic ulcer related to amputation. OTR4120 was applied twice a week or until complete healing, for up to 12 weeks. Ulcer surface area reduction (%)after 2, 4, 8 and 12 weeks, appearance after 4 weeks, and healing after 12 weeks were measured and recorded. RESULTS: A 35% reduction in ulcer size was achieved after 4 weeks. 7 (50%) out of 14 ulcers completely healed within 1 to 3 months of treatment. DISCUSSION: OTR4120 is an effective therapeutic option for patients with chronic lower extremity ulcers, can provide major improvement of quality of life and has the added benefit of being a significant cost-effective solution for healthcare systems.

18.
Blood Adv ; 3(22): 3780-3817, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31770441

RESUMO

Over the last decade, there have been numerous developments and changes in treatment practices for the management of patients with immune thrombocytopenia (ITP). This article is an update of the International Consensus Report published in 2010. A critical review was performed to identify all relevant articles published between 2009 and 2018. An expert panel screened, reviewed, and graded the studies and formulated the updated consensus recommendations based on the new data. The final document provides consensus recommendations on the diagnosis and management of ITP in adults, during pregnancy, and in children, as well as quality-of-life considerations.


Assuntos
Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Tomada de Decisão Clínica , Terapia Combinada , Árvores de Decisões , Gerenciamento Clínico , Humanos , Púrpura Trombocitopênica Idiopática/etiologia , Índice de Gravidade de Doença , Resultado do Tratamento
19.
Am J Hematol ; 94(12): 1314-1324, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31489694

RESUMO

Rituximab is a second-line option in adults with immune thrombocytopenia (ITP), but the estimated 5-year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long-term safety. We conducted a prospective multicenter registry of 248 adults with ITP treated with rituximab with 5 years of follow-up to assess its long-term safety and efficacy. The median follow-up was 68.4 [53.7-78.5] months. The incidence of severe infections was only 2/100 patient-years. Profound hypogammaglobulinemia (<5 g/L) developed in five patients at 15 to 31 months after the last rituximab infusion. In total, 25 patients died at a median age of 80 [69.5-83.9] years, corresponding to a mortality rate of 2.3/100 patient-years. Only three deaths related to infection that occurred 12 to 14 months after rituximab infusions could be due in part to rituximab. At 60 months of follow-up, 73 (29.4%) patients had a sustained response. On univariate and multivariate analysis, the only factor significantly associated with sustained response was a previous transient response to corticosteroids (P = .022). Overall, 24 patients with an initial response and then relapse received retreatment with rituximab, which gave a response in 92%, with a higher duration of response in 54%. As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP. Retreatment could be an effective and safe option.


Assuntos
Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Rituximab/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Agamaglobulinemia/induzido quimicamente , Agamaglobulinemia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Causas de Morte , Intervalo Livre de Doença , Erupção por Droga/epidemiologia , Erupção por Droga/etiologia , Substituição de Medicamentos , Feminino , Seguimentos , França/epidemiologia , Humanos , Infecções/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/etiologia , Neoplasias/imunologia , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/mortalidade , Sistema de Registros , Rituximab/efeitos adversos , Doença do Soro/induzido quimicamente , Doença do Soro/epidemiologia
20.
Br J Haematol ; 187(1): 124-128, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31155716

RESUMO

We report the off-label use of bortezomib combined with dexamethasone in eight adults with severe and multi-refractory warm auto-immune haemolytic anaemia (wAIHA). After six cycles of induction therapy, 6 of the 8 patients achieved response (3 complete response, 3 response). Response was obtained after a median of 2 (1-4) cycles. After a median follow-up of 14 (6-36) months, six patients maintained a response (bortezomib/dexamethasone maintenance, n = 4); five patients experienced at least one moderate adverse event, including peripheral neuropathy (n = 2). These results suggest that bortezomib/dexamethasone combination is a promising approach with acceptable toxicity for treating severe refractory wAIHA in adults.


Assuntos
Anemia Hemolítica Autoimune/tratamento farmacológico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Adulto , Idoso , Anemia Hemolítica Autoimune/sangue , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Uso Off-Label , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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