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Survival of AIDS‐related diffuse large B‐cell lymphoma,Burkitt lymphoma,and plasmablastic lymphoma in the German HIV Lymphoma Cohort
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Christian Hoffmann Daniel Gillor Alexander Zoufaly Björn Jensen Johannes R. Bogner Jan Thoden Jan‐Christian Wasmuth Timo Wolf Mark Oette Markus Müller Stefan Esser Jörg J. Vehreschild Gerd Fätkenheuer Christoph Wyen 《British journal of haematology》2015,168(6):806-810
Overall survival (OS) of patients with acquired immunodeficiency syndrome (AIDS)‐related Burkitt lymphoma (BL), diffuse large B‐cell lymphoma (DLBCL) and plasmablastic lymphoma (PBL) was analysed in the German AIDS‐related‐Lymphoma‐Cohort‐Study. Of 291 patients prospectively included between January 2005 and December 2012, 154 had DLBCL, 103 BL and 34 PBL. Two‐year OS rates were similar between BL (69%) and DLBCL patients (63%) but lower for PBL patients (43%). Intermediate (Hazard ratio [HR] 4·1 95% confidence interval [CI] 1·98–8·49) or high (HR 4·92 95% CI 2·1–11·61) International Prognostic Index, bone marrow involvement (HR 1·69 95% CI 1·00–2·84) and PBL histology (HR 2·24 95% CI 1·24–4·03) were independent predictors of mortality. 相似文献
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Immunotherapy with the trifunctional anti‐CD20 x anti‐CD3 antibody FBTA05 (Lymphomun) in paediatric high‐risk patients with recurrent CD20‐positive B cell malignancies
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Wilhelm Woessmann Beate Winkler Meinolf Siepermann Roland Meisel Paul G. Schlegel Jürgen Hess Horst Lindhofer Arndt Borkhardt Raymund Buhmann 《British journal of haematology》2015,169(1):90-102
Children with B cell malignancies refractory to standard therapy are known to have a poor prognosis and very limited treatment options. Here, we report on the treatment and follow‐up of ten patients diagnosed with relapsed or refractory mature B‐cell Non Hodgkin Lymphoma (B‐NHL), Burkitt leukaemia (B‐AL) or pre B‐acute lymphoblastic leukaemia (pre B‐ALL). All children were treated with FBTA05 (now designated Lymphomun), an anti‐CD3 x anti‐CD20 trifunctional bispecific antibody (trAb) in compassionate use. Within individual treatment schedules, Lymphomun was applied (a) after allogeneic stem cell transplantation (allo‐SCT, n = 6) to induce sustained long‐term remission, or (b) stand alone prior to subsequent chemotherapy to eradicate residual disease before allo‐SCT (n = 4). Nine of ten children displayed a clinical response: three stable diseases (SD), one partial remission (PR) and five induced or sustained complete remissions (CR). Five of these nine responders died during follow‐up. The other patients still maintain CR with a current overall survival of 874–1424 days (median: 1150 days). In conclusion, despite the dismal clinical prognosis of children refractory to standard therapy, immunotherapy with Lymphomun resulted in a favourable clinical outcome in this cohort of refractory paediatric patients. 相似文献
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Infections after T‐replete haploidentical transplantation and high‐dose cyclophosphamide as graft‐versus‐host disease prophylaxis
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R. Crocchiolo S. Bramanti A. Vai B. Sarina R. Mineri E. Casari F. Tordato E. Mauro I. Timofeeva E. Lugli D. Mavilio C. Carlo‐Stella A. Santoro L. Castagna 《Transplant infectious disease》2015,17(2):242-249
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Bertrand Coiffier John Radford André Bosly Giovanni Martinelli Gabriela Barca Andrew Davies Didier Decaudin Eve Gallop‐Evans Swaminathan Padmanabhan‐Iyer Koen Van Eygen Ka Lung Wu Ira V. Gupta Thomas S. Lin Nancy Goldstein Roxanne C. Jewell Paul Winter Steen Lisby study investigators 《British journal of haematology》2013,163(3):334-342
This international, multicentre phase II study was conducted to assess ofatumumab, a human anti‐CD20 monoclonal antibody, in patients with relapsed/progressive diffuse large B‐cell lymphoma (DLBCL) who were ineligible for autologous stem cell transplantation (TI) or who had relapse/progression after transplantation (PT). Eighty‐one patients received ofatumumab 300 mg intravenously (IV) on Day 1, followed by seven weekly IV infusions of 1000 mg. Patients in the TI and PT groups had received a median of 3 (range, 1–7) and 5 (range, 2–7) prior therapies, respectively. One‐third of patients did not respond to the last prior therapy, and 53% had failed two or more rituximab‐containing therapies. Overall response rate was 13% for the TI group (seven partial responses) and 8% for the PT group (two complete responses). Median progression‐free survival was 2·6 months, and median duration of response was 9·5 months. The most common Grade 3–4 adverse events were neutropenia (11%), leucopenia (6%), lymphopenia (6%) and thrombocytopenia (6%). Sixteen deaths have been reported, with disease progression as the most common cause of death. In conclusion, ofatumumab monotherapy was well tolerated and provided clinical benefit to some DLBCL patients in this study. This trial was registered at www.clinicaltrials.gov (NCT00622388). 相似文献
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Elevated AST‐to‐platelet ratio index is associated with increased all‐cause mortality among HIV‐infected adults in Zambia
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Michael J. Vinikoor Edford Sinkala Aggrey Mweemba Arianna Zanolini Lloyd Mulenga Izukanji Sikazwe Michael W. Fried Joseph J. Eron Gilles Wandeler Benjamin H. Chi 《Liver international》2015,35(7):1886-1892
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Grabar S Lanoy E Allavena C Mary-Krause M Bentata M Fischer P Mahamat A Rabaud C Costagliola D;Clinical Epidemiology Group of the French Hospital Database on HIV 《HIV medicine》2008,9(4):246-256
OBJECTIVES: To analyse the impact of combined antiretroviral treatment (cART) on survival with AIDS, according to the nature of the first AIDS-defining clinical illness (ADI); to examine trends in AIDS-defining causes (ADC) and non-AIDS-defining causes (non-ADC) of death. METHODS: From the French Hospital Database on HIV, we studied trends in the nature of the first ADI and subsequent survival in France during three calendar periods: the pre-cART period (1993-1995; 8027 patients), the early cART period (1998-2000; 3504 patients) and the late cART period (2001-2003; 2936 patients). RESULTS: The three most frequent initial ADIs were Pneumocystis carinii (jirovecii) pneumonia (PCP) (15.6%), oesophageal candidiasis (14.3%) and Kaposi's sarcoma (13.9%) in the pre-cART period. In the late cART period, the most frequent ADIs were tuberculosis (22.7%), PCP (19.1%) and oesophageal candidiasis (16.2%). The risk of death after a first ADI fell significantly after the arrival of cART. Lower declines were observed for progressive multifocal leukoencephalopathy, lymphoma and Mycobacterium avium complex infection. After an ADI, the 3-year risk of death from an ADC fell fivefold between the pre-cART and late cART periods (39%vs. 8%), and fell twofold for non-ADCs (17%vs. 9%). CONCLUSIONS: The relative frequencies of initial ADI have changed since the advent of cART. Tuberculosis is now the most frequent initial ADI in France; this is probably the result of the increasing proportion of migrants from sub-Saharan Africa. After a first ADI, cART has a major impact on ADCs and a smaller impact on deaths from other causes. The risk of death from AIDS and from other causes is now similar. 相似文献
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Objectives
While highly active antiretroviral therapy (HAART) decreases long‐term morbidity and mortality, its short‐term effect on hospitalization rates is unknown. The primary objective of this study was to determine hospitalization rates over time in the year after HAART initiation for virological responders and nonresponders.Methods
Hospitalizations among 1327 HAART‐naïve subjects in an urban HIV clinic in 1997–2007 were examined before and after HAART initiation. Hospitalization rates were stratified by virological responders (≥1 log10 decrease in HIV‐1 RNA within 6 months after HAART initiation) and nonresponders. Causes were determined through International Classification of Diseases, 9th Revision (ICD‐9) codes and chart review. Multivariate negative binomial regression was used to assess factors associated with hospitalization.Results
During the first 45 days after HAART initiation, the hospitalization rate of responders was similar to their pre‐HAART baseline rate [75.1 vs. 78.8/100 person‐years (PY)] and to the hospitalization rate of nonresponders during the first 45 days (79.4/100 PY). The hospitalization rate of responders fell significantly between 45 and 90 days after HAART initiation and reached a plateau at approximately 45/100 PY from 91 to 365 days after HAART initiation. Significant decreases were seen in hospitalizations for opportunistic and nonopportunistic infections.Conclusions
The first substantial clinical benefit from HAART may be realized by 90 days after HAART initiation; providers should keep close vigilance at least until this time.14.
Patient perspectives on de‐simplifying their single‐tablet co‐formulated antiretroviral therapy for societal cost savings
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Objectives
The incremental costs of expanding antiretroviral (ARV) drug treatment to all HIV‐infected patients are substantial, so cost‐saving initiatives are important. Our objectives were to determine the acceptability and financial impact of de‐simplifying (i.e. switching) more expensive single‐tablet formulations (STFs) to less expensive generic‐based multi‐tablet components. We determined physician and patient perceptions and acceptance of STF de‐simplification within the context of a publicly funded ARV budget.Methods
Programme costs were calculated for patients on ARVs followed at the Southern Alberta Clinic, Canada during 2016 (Cdn$). We focused on patients receiving Triumeq® and determined the savings if patients de‐simplified to eligible generic co‐formulations. We surveyed all prescribing physicians and a convenience sample of patients taking Triumeq® to see if, for budgetary purposes, they felt that de‐simplification would be acceptable.Results
Of 1780 patients receiving ARVs, 62% (n = 1038) were on STF; 58% (n = 607) of patients on STF were on Triumeq®. The total annual cost of ARVs was $26 222 760. The cost for Triumeq® was $8 292 600. If every patient on Triumeq® switched to generic abacavir/lamivudine and Tivicay® (dolutegravir), total costs would decrease by $4 325 040. All physicians (n = 13) felt that de‐simplifying could be safely achieved. Forty‐eight per cent of 221 patients surveyed were agreeable to de‐simplifying for altruistic reasons, 27% said no, and 25% said maybe.Conclusions
De‐simplifying Triumeq® generates large cost savings. Additional savings could be achieved by de‐simplifying other STFs. Both physicians and patients agreed that selective de‐simplification was acceptable; however, it may not be acceptable to every patient. Monitoring the medical and cost impacts of de‐simplification strategies seems warranted.15.
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《British journal of haematology》2018,181(1):38-53
New immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long‐term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co‐inhibitory signalling pathways have been shown to play a crucial role. Via up‐regulation of inhibitory checkpoints, tumour‐reactive T cell and Natural Killer cell responses can be strongly impeded. Accordingly, the introduction of checkpoint inhibitors targeting CTLA‐4 (CTLA4) and PD‐1 (PDCD1, CD279)/PD‐L1 (CD274, PDCD1LG1) accomplished a breakthrough in cancer treatment, with impressive clinical responses. Numerous new co‐inhibitory players and novel combination therapies are currently investigated for their potential to boost anti‐tumour immunity and improve survival of cancer patients. Although the challenge here remains to avoid severe systemic toxicity. This review addresses the involvement of co‐inhibitory signalling in AML immune evasion and discusses the opportunities for checkpoint blockers in AML treatment. 相似文献
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Edouard Cornet Cécile Tomowiak Aline Tanguy‐Schmidt Stéphane Lepretre Jehan Dupuis Pierre Feugier Alain Devidas Clara Mariette Véronique Leblond Catherine Thiéblemont Patricia Validire‐Charpy Laurent Sutton Emmanuel Gyan Jean‐Claude Eisenmann Pascale Cony‐Makhoul Loïc Ysebaert Xavier Troussard the Société Française d'Hématologie 《British journal of haematology》2014,166(3):390-400
A large, multicentre, retrospective survey of patients with hairy cell leukaemia (HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long‐term effects of the established purine nucleoside analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL. Of the patients included in the survey, 18% (88/487) had a familial history of cancers, 8% (41/487) presented with malignancies before HCL diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed. An excess incidence of second malignancies was observed, with a standardized incidence ratio (SIR) of 1·86 (95% confidence interval (CI): 1·34–2·51), with no significant difference between PNAs. For second haematological malignancies alone, the SIR was markedly increased at 5·32 (95% CI: 2·90–8·92). This study highlights the high frequency of cancers in HCL patients and their family members. The frequency of second malignancies is notably increased, particularly for haematological malignancies. The respective role of pentostatin and cladribine in the development of second malignancies is debatable. 相似文献