Pub Date : 2024-08-01Epub Date: 2024-06-12DOI: 10.1016/S2352-3026(24)00167-4
Rafael S Cires-Drouet
{"title":"Anticoagulation in patients with inferior vena cava agenesia.","authors":"Rafael S Cires-Drouet","doi":"10.1016/S2352-3026(24)00167-4","DOIUrl":"10.1016/S2352-3026(24)00167-4","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e555-e556"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/S2352-3026(24)00217-5
Emma Wilkinson
{"title":"Aaron Goodman: \"people tell me they've been waiting for someone to speak up\".","authors":"Emma Wilkinson","doi":"10.1016/S2352-3026(24)00217-5","DOIUrl":"10.1016/S2352-3026(24)00217-5","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 8","pages":"e563"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-02DOI: 10.1016/S2352-3026(24)00144-3
Bruno Fattizzo, Monia Marchetti, Marc Michel, Silvia Cantoni, Henrik Frederiksen, Giulio Giordano, Andreas Glenthøj, Tomás José González-López, Irina Murakhovskaya, Mariasanta Napolitano, Maria-Eva Mingot, Maria Arguello, Andrea Patriarca, Simona Raso, Nicola Vianelli, Wilma Barcellini
Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice.
{"title":"Diagnosis and management of Evans syndrome in adults: first consensus recommendations.","authors":"Bruno Fattizzo, Monia Marchetti, Marc Michel, Silvia Cantoni, Henrik Frederiksen, Giulio Giordano, Andreas Glenthøj, Tomás José González-López, Irina Murakhovskaya, Mariasanta Napolitano, Maria-Eva Mingot, Maria Arguello, Andrea Patriarca, Simona Raso, Nicola Vianelli, Wilma Barcellini","doi":"10.1016/S2352-3026(24)00144-3","DOIUrl":"10.1016/S2352-3026(24)00144-3","url":null,"abstract":"<p><p>Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e617-e628"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-06-12DOI: 10.1016/S2352-3026(24)00138-8
Carlos Bravo-Pérez, Ana Blanco, Nuria Revilla, Jorge Cobos, Alba Salgado-Parente, Susana Asenjo, Ramiro Méndez, Luis Marti-Bonmati, Santiago Bonanad, José C Albillos, Nerea Castro, Shally Marcellini, Paul López Sala, Maialen Lasa, José M Bastida, María S Infante, Miguel A Corral, Javier Pagan, Pilar Llamas, Juan J Rodríguez-Sevilla, Agustín Rodríguez-Alen, Teresa S Sevivas, Daniela Morello, Cristina García Villar, Sara Lojo, Ana Marco, Paolo Simioni, Vicente Vicente, María L Lozano, María E de la Morena-Barrio, José M García-Santos, Javier Corral
<p><strong>Background: </strong>Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA.</p><p><strong>Methods: </strong>In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing.</p><p><strong>Findings: </strong>We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p<0·0001). Analysis of 126 patients with venous thrombosis pooled from cohorts A and B showed early-onset (median age 34·6 years, IQR 23·3-54·3) and recurrent events (50 [40%] of 126 patients). Patients with extrahepatic IVCA had greater proportions of lower-limb venous thrombosis (95 [87%] of 109 vs nine [53%] of 17, p=0·0010) and recurrence (48 [44%] of 109 vs two [12%] of 17, p=0·015), but lower rates of pulmonary embolism (10 [10%] of 99 vs four [33%] of 12, p=0·044) than did patients with hepatic IVCA. 77 (63%) of 122 patients with thrombosis underwent indefinite anticoagulation. 32 (29%) of 111 patients (29 [34%] of 86 with thrombosis) had coexisting thrombophilias. The recurrence risk was lower for patients receiving indefinite anticoagulation (adjusted odds ratio 0·24, 95% CI 0·08-0·61; p=0·010), and greater for thrombophilias (3·19, 1·09-9·32; p=0·034).</p><p><strong>Interpretation: </strong>This evaluation of a large p
{"title":"Thrombotic risk and features of patients with inferior vena cava agenesis: a multicentre, retrospective, observational study.","authors":"Carlos Bravo-Pérez, Ana Blanco, Nuria Revilla, Jorge Cobos, Alba Salgado-Parente, Susana Asenjo, Ramiro Méndez, Luis Marti-Bonmati, Santiago Bonanad, José C Albillos, Nerea Castro, Shally Marcellini, Paul López Sala, Maialen Lasa, José M Bastida, María S Infante, Miguel A Corral, Javier Pagan, Pilar Llamas, Juan J Rodríguez-Sevilla, Agustín Rodríguez-Alen, Teresa S Sevivas, Daniela Morello, Cristina García Villar, Sara Lojo, Ana Marco, Paolo Simioni, Vicente Vicente, María L Lozano, María E de la Morena-Barrio, José M García-Santos, Javier Corral","doi":"10.1016/S2352-3026(24)00138-8","DOIUrl":"10.1016/S2352-3026(24)00138-8","url":null,"abstract":"<p><strong>Background: </strong>Inferior vena cava agenesis (IVCA) is a rare anomaly predisposing affected people to lower-limb venous thrombosis with low frequency of pulmonary embolism. Antenatal thrombosis and inherited thrombophilia have been suggested as causes of IVCA. However, there is little evidence on the clinical course and management of this condition. We designed a patient registry to assess the thrombotic risk and features of IVCA.</p><p><strong>Methods: </strong>In this this multicentre, retrospective, observational study, we included patients with IVCA diagnosed by routine imaging from 20 hospitals in Spain (n=18), Portugal (n=1), and Italy (n=1). Patients were identified from a systematic search in radiology databases using data extraction software (cohort A) and alternative searches in medical records for confirmed IVCA (cohort B; option allowed when systematic approaches were unapplicable). Primary outcomes were clinical and imaging features, thrombotic risk, phenotype of IVCA-associated thrombosis, anticoagulant treatment, and the results of thrombophilia testing.</p><p><strong>Findings: </strong>We included patients with IVCA diagnosed by routine imaging studies done between Jan 1, 2010, and Dec 31, 2022. In the systematic search, 4 341 333 imaging exams were screened from the radiology databases of eight centres. 122 eligible patients were enrolled in cohort A. A further 95 patients were identified by screening medical records at 12 centres, of whom 88 were eligible and included in cohort B, making a combined cohort of 210 patients. 96 (46%) of 210 patients were female and 200 (95%) were European or Hispanic. 60 (29%) of 210 patients had hepatic IVC interruption, whereas 150 (71%) had extrahepatic IVCA. In cohort A, 65 (53%) of 122 patients had venous thrombosis, with an estimated annual risk of 1·15% (95% CI 0·89-1·46). Extrahepatic IVCA was associated with a greater risk of venous thrombosis than hepatic IVCA (56 [67%] of 84 patients vs nine [24%] of 38 patients, odds ratio 5·31, 95% CI 2·27-12·43; p<0·0001). Analysis of 126 patients with venous thrombosis pooled from cohorts A and B showed early-onset (median age 34·6 years, IQR 23·3-54·3) and recurrent events (50 [40%] of 126 patients). Patients with extrahepatic IVCA had greater proportions of lower-limb venous thrombosis (95 [87%] of 109 vs nine [53%] of 17, p=0·0010) and recurrence (48 [44%] of 109 vs two [12%] of 17, p=0·015), but lower rates of pulmonary embolism (10 [10%] of 99 vs four [33%] of 12, p=0·044) than did patients with hepatic IVCA. 77 (63%) of 122 patients with thrombosis underwent indefinite anticoagulation. 32 (29%) of 111 patients (29 [34%] of 86 with thrombosis) had coexisting thrombophilias. The recurrence risk was lower for patients receiving indefinite anticoagulation (adjusted odds ratio 0·24, 95% CI 0·08-0·61; p=0·010), and greater for thrombophilias (3·19, 1·09-9·32; p=0·034).</p><p><strong>Interpretation: </strong>This evaluation of a large p","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e606-e616"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/S2352-3026(24)00219-9
Siana Nkya, Upendo Masamu, Patience Kuona, Sarah Kiguli, Aldiouma Guindo, Fred Stephen Sarfo, Obiageli Nnodu, Ambroise Wonkam, Emmanuel Balandya, Julie Makani
{"title":"Update on SickleInAfrica: a collaborative and multidimensional approach to conduct research and improve health.","authors":"Siana Nkya, Upendo Masamu, Patience Kuona, Sarah Kiguli, Aldiouma Guindo, Fred Stephen Sarfo, Obiageli Nnodu, Ambroise Wonkam, Emmanuel Balandya, Julie Makani","doi":"10.1016/S2352-3026(24)00219-9","DOIUrl":"10.1016/S2352-3026(24)00219-9","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 8","pages":"e565-e566"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-10DOI: 10.1016/S2352-3026(24)00174-1
Franco Locatelli, Bulent Antmen, Hyoung Jin Kang, Katsuyoshi Koh, Yoshiyuki Takahashi, Alphan Kupesiz, Maria Gabriela A Dias Matos, Yogi Chopra, Sunil Bhat, Ho Joon Im, Tayfun Güngör, Meng-Yao Lu, Tommaso Stefanelli, Christine Rosko, Annie St Pierre, Karin Burock, Yvonne Smith, Karen Sinclair, Cristina Diaz-de-Heredia
<p><strong>Background: </strong>Chronic graft-versus-host disease (GVHD) is a debilitating, and sometimes life threatening, complication of allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the activity, pharmacokinetics, and safety of ruxolitinib added to corticosteroids in paediatric patients (ie, <18 years) with moderate-to-severe chronic GVHD.</p><p><strong>Methods: </strong>In this single-arm, phase 2 study, patients were recruited at 21 hospitals or clinics across 14 countries in Asia, Europe, and Canada. Eligible patients were aged 28 days to younger than 18 years, had undergone allogenic HSCT, and had been diagnosed with treatment-naive or corticosteroid-refractory moderate-to-severe chronic GVHD, per 2014 National Institutes of Health consensus criteria. Patients received oral ruxolitinib dosing on the basis of their age at the start of treatment: those aged 12 years to younger than 18 years received 10 mg twice daily (age ≥12 to <18 years group), those aged 6 years to younger than 12 years (age ≥6 to <12 years group) received 5 mg twice daily, and those aged 2 years to younger than 6 years received 4 mg/m<sup>2</sup> twice daily (age ≥2 to <6 years group). Treatment was to be administered in 28-day cycles for approximately 36 months, alongside supportive treatment per institutional guidelines. The primary activity endpoint was overall response rate at cycle 7 day 1. Activity and safety analyses are reported in the full analysis set, which included all patients who received at least one dose of ruxolitinib. Here we report the prespecified interim analysis, scheduled to occur after all patients had completed 1 year of treatment or discontinued treatment, and the results for the primary endpoint evaluation reported here is to be considered final. This study is registered with ClinicalTrials.gov, NCT03774082, enrolment is complete, and the study is ongoing.</p><p><strong>Findings: </strong>Between May 20, 2020, and Sept 17, 2021, 48 patients were screened, of whom 45 were enrolled and received at least one dose of study drug (median age was 11·0 years [IQR 7·2-14·3], 16 [36%] were female, 29 [64%] were male, 21 [47%] were White, one [2%] was Black or African American, 23 [51%] were Asian, 17 [38%] were treatment-naive, 28 [62%] were corticosteroid-refractory). As of data cutoff (Oct 19, 2022), after a median ruxolitinib exposure of 55·1 weeks (IQR 13·1-75·3), the overall response rate at cycle 7 day 1 was 40·0% (18 of 45; 90% CI 27·7-53·3), with responses seen in seven (41%) of 17 treatment-naive patients and 11 (39%) of 28 corticosteroid-refractory patients. The most common treatment-related adverse events of grade 3 or worse were neutropenia (eight [18%] of 45) and thrombocytopenia (six [13%]). Seven (16%) patients had grade 3 or worse serious treatment-related adverse events; the most common was hyponatraemia (two [4%] of 45). Three (7%) patients died while on-treatment (within 30 days of treatment disco
背景：慢性移植物抗宿主疾病（GVHD）是异基因造血干细胞移植（HSCT）的一种致残性并发症，有时甚至危及生命。我们的目的是研究鲁索利替尼在皮质类固醇治疗中的活性、药代动力学和安全性：在这项单臂2期研究中，亚洲、欧洲和加拿大14个国家的21家医院或诊所招募了患者。符合条件的患者年龄在28天至18岁之间，接受过异基因造血干细胞移植，并根据2014年美国国立卫生研究院共识标准被诊断为无治疗或皮质类固醇难治性中重度慢性GVHD。患者根据开始治疗时的年龄接受鲁索利替尼口服给药：年龄在12岁至18岁以下的患者每天两次，每次10毫克（年龄≥12岁的患者每天两次，每次2毫克），年龄≥2岁至18岁的患者每天两次，每次2毫克（年龄≥18岁的患者每天两次，每次2毫克）：2020年5月20日至2021年9月17日期间，共筛选出48名患者，其中45名患者入组并接受了至少一次剂量的研究药物治疗（中位年龄为11-0岁[IQR 7-2-14-3]，16名[36%]为女性，29名[64%]为男性，21名[47%]为白人，1名[2%]为黑人或非裔美国人，23名[51%]为亚裔，17名[38%]为未接受治疗者，28名[62%]为皮质类固醇难治性患者）。截至数据截止日（2022年10月19日），中位ruxolitinib暴露55-1周（IQR 13-1-75-3）后，第7周期第1天的总体应答率为40-0%（45例中有18例；90% CI 27-7-53-3），17例非治疗依赖患者中有7例（41%）出现应答，28例皮质类固醇难治患者中有11例（39%）出现应答。最常见的3级或更严重的治疗相关不良反应是中性粒细胞减少（45例中有8例[18%]）和血小板减少（6例[13%]）。7名患者（16%）出现了3级或更严重的严重治疗相关不良事件；最常见的是低钠血症（45人中有2人[4%]）。3名（7%）患者在治疗期间（治疗停止后30天内）死亡，其中1人死于曲霉菌感染，1人死于脓毒性休克，1人死于急性呼吸窘迫综合征；均不认为与研究药物有关：在最终分析之前，这项研究表明，对于年龄在2岁至18岁之间的慢性GVHD患者，无论是无治疗史还是皮质类固醇难治性患者，Ruxolitinib都具有良好的活性和耐受性，因此支持在这一患者群体中使用Ruxolitinib。Ruxolitinib在这一患者群体中的安全性与成人一致。这项研究的最终分析结果将进一步说明Ruxolitinib在慢性GVHD儿童患者中的长期疗效：Novartis.
{"title":"Ruxolitinib in treatment-naive or corticosteroid-refractory paediatric patients with chronic graft-versus-host disease (REACH5): interim analysis of a single-arm, multicentre, phase 2 study.","authors":"Franco Locatelli, Bulent Antmen, Hyoung Jin Kang, Katsuyoshi Koh, Yoshiyuki Takahashi, Alphan Kupesiz, Maria Gabriela A Dias Matos, Yogi Chopra, Sunil Bhat, Ho Joon Im, Tayfun Güngör, Meng-Yao Lu, Tommaso Stefanelli, Christine Rosko, Annie St Pierre, Karin Burock, Yvonne Smith, Karen Sinclair, Cristina Diaz-de-Heredia","doi":"10.1016/S2352-3026(24)00174-1","DOIUrl":"10.1016/S2352-3026(24)00174-1","url":null,"abstract":"<p><strong>Background: </strong>Chronic graft-versus-host disease (GVHD) is a debilitating, and sometimes life threatening, complication of allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the activity, pharmacokinetics, and safety of ruxolitinib added to corticosteroids in paediatric patients (ie, <18 years) with moderate-to-severe chronic GVHD.</p><p><strong>Methods: </strong>In this single-arm, phase 2 study, patients were recruited at 21 hospitals or clinics across 14 countries in Asia, Europe, and Canada. Eligible patients were aged 28 days to younger than 18 years, had undergone allogenic HSCT, and had been diagnosed with treatment-naive or corticosteroid-refractory moderate-to-severe chronic GVHD, per 2014 National Institutes of Health consensus criteria. Patients received oral ruxolitinib dosing on the basis of their age at the start of treatment: those aged 12 years to younger than 18 years received 10 mg twice daily (age ≥12 to <18 years group), those aged 6 years to younger than 12 years (age ≥6 to <12 years group) received 5 mg twice daily, and those aged 2 years to younger than 6 years received 4 mg/m<sup>2</sup> twice daily (age ≥2 to <6 years group). Treatment was to be administered in 28-day cycles for approximately 36 months, alongside supportive treatment per institutional guidelines. The primary activity endpoint was overall response rate at cycle 7 day 1. Activity and safety analyses are reported in the full analysis set, which included all patients who received at least one dose of ruxolitinib. Here we report the prespecified interim analysis, scheduled to occur after all patients had completed 1 year of treatment or discontinued treatment, and the results for the primary endpoint evaluation reported here is to be considered final. This study is registered with ClinicalTrials.gov, NCT03774082, enrolment is complete, and the study is ongoing.</p><p><strong>Findings: </strong>Between May 20, 2020, and Sept 17, 2021, 48 patients were screened, of whom 45 were enrolled and received at least one dose of study drug (median age was 11·0 years [IQR 7·2-14·3], 16 [36%] were female, 29 [64%] were male, 21 [47%] were White, one [2%] was Black or African American, 23 [51%] were Asian, 17 [38%] were treatment-naive, 28 [62%] were corticosteroid-refractory). As of data cutoff (Oct 19, 2022), after a median ruxolitinib exposure of 55·1 weeks (IQR 13·1-75·3), the overall response rate at cycle 7 day 1 was 40·0% (18 of 45; 90% CI 27·7-53·3), with responses seen in seven (41%) of 17 treatment-naive patients and 11 (39%) of 28 corticosteroid-refractory patients. The most common treatment-related adverse events of grade 3 or worse were neutropenia (eight [18%] of 45) and thrombocytopenia (six [13%]). Seven (16%) patients had grade 3 or worse serious treatment-related adverse events; the most common was hyponatraemia (two [4%] of 45). Three (7%) patients died while on-treatment (within 30 days of treatment disco","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e580-e592"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-10DOI: 10.1016/S2352-3026(24)00206-0
Luisa Sisinni
{"title":"Ruxolitinib: a game changer in paediatric chronic graft-versus-host disease management?","authors":"Luisa Sisinni","doi":"10.1016/S2352-3026(24)00206-0","DOIUrl":"10.1016/S2352-3026(24)00206-0","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e553-e555"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01Epub Date: 2024-07-04DOI: 10.1016/S2352-3026(24)00214-X
Yaiza Del Pozo Martín, Emma Cookson
{"title":"European Hematology Association 2024 Hybrid Congress.","authors":"Yaiza Del Pozo Martín, Emma Cookson","doi":"10.1016/S2352-3026(24)00214-X","DOIUrl":"10.1016/S2352-3026(24)00214-X","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e561-e562"},"PeriodicalIF":15.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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