Pub Date : 2024-07-01DOI: 10.1016/S2352-3026(24)00184-4
Talha Burki
{"title":"Don Thomas: leading the charge to bone marrow transplantation.","authors":"Talha Burki","doi":"10.1016/S2352-3026(24)00184-4","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00184-4","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 7","pages":"e485-e486"},"PeriodicalIF":15.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471798","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 : 2024-07-01DOI: 10.1016/S2352-3026(24)00104-2
Teresa Calimeri, Nicoletta Anzalone, Maria Giulia Cangi, Paolo Fiore, Filippo Gagliardi, Elisabetta Miserocchi, Maurilio Ponzoni, Andrés J M Ferreri
Early diagnosis is crucial for the successful treatment of primary CNS lymphoma (PCNSL), a rapidly progressing tumour. Suspicion raised on brain MRI must be confirmed by a histopathological diagnosis of a tumour specimen collected by stereotactic biopsy. In rare cases, cerebrospinal fluid (CSF) or vitreous humour might aid in providing a cytological diagnosis. Several disease-related, patient-related, and treatment-related factors affect the timing and accuracy of diagnosis and patient outcome. Some molecules detected in CSF, aqueous and vitreous humour, and peripheral blood were proposed as diagnostic biomarkers for PCNSL; however, detection methods for most of these molecules are not yet standardised, have a long turnaround time, are expensive, and have little reproducibility among labs. By contrast, the MYD88Leu265Pro somatic hotspot mutation, revealed by PCR-based assay, is currently and reliably used during the diagnosis of some lymphomas, and IL-10, measured by enzyme-linked immunosorbent assay, is routinely used to diagnose and monitor different common metabolic and immunological diseases. Several independent studies have shown that MYD88Leu265Pro and IL-10 can be easily assessed in peripheral blood, plasma, aqueous and vitreous humour, and CSF of patients with PCNSL with substantial sensitivity and specificity, especially when evaluated in combination. In this Viewpoint, evidence supporting the routine use of MYD88Leu265Pro and IL-10 in diagnosing PCNSL is considered, and some examples of the frequent difficulties found in the diagnosis of PCNSL are provided, highlighting the role and indications of these two biomarkers to improve the timely recognition of this aggressive tumour.
{"title":"Molecular diagnosis of primary CNS lymphoma in 2024 using MYD88<sup>Leu265Pro</sup> and IL-10.","authors":"Teresa Calimeri, Nicoletta Anzalone, Maria Giulia Cangi, Paolo Fiore, Filippo Gagliardi, Elisabetta Miserocchi, Maurilio Ponzoni, Andrés J M Ferreri","doi":"10.1016/S2352-3026(24)00104-2","DOIUrl":"10.1016/S2352-3026(24)00104-2","url":null,"abstract":"<p><p>Early diagnosis is crucial for the successful treatment of primary CNS lymphoma (PCNSL), a rapidly progressing tumour. Suspicion raised on brain MRI must be confirmed by a histopathological diagnosis of a tumour specimen collected by stereotactic biopsy. In rare cases, cerebrospinal fluid (CSF) or vitreous humour might aid in providing a cytological diagnosis. Several disease-related, patient-related, and treatment-related factors affect the timing and accuracy of diagnosis and patient outcome. Some molecules detected in CSF, aqueous and vitreous humour, and peripheral blood were proposed as diagnostic biomarkers for PCNSL; however, detection methods for most of these molecules are not yet standardised, have a long turnaround time, are expensive, and have little reproducibility among labs. By contrast, the MYD88<sup>Leu265Pro</sup> somatic hotspot mutation, revealed by PCR-based assay, is currently and reliably used during the diagnosis of some lymphomas, and IL-10, measured by enzyme-linked immunosorbent assay, is routinely used to diagnose and monitor different common metabolic and immunological diseases. Several independent studies have shown that MYD88<sup>Leu265Pro</sup> and IL-10 can be easily assessed in peripheral blood, plasma, aqueous and vitreous humour, and CSF of patients with PCNSL with substantial sensitivity and specificity, especially when evaluated in combination. In this Viewpoint, evidence supporting the routine use of MYD88<sup>Leu265Pro</sup> and IL-10 in diagnosing PCNSL is considered, and some examples of the frequent difficulties found in the diagnosis of PCNSL are provided, highlighting the role and indications of these two biomarkers to improve the timely recognition of this aggressive tumour.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 7","pages":"e540-e549"},"PeriodicalIF":15.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471802","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 : 2024-07-01Epub Date: 2024-06-07DOI: 10.1016/S2352-3026(24)00181-9
The Lancet Haematology
{"title":"UK tainted blood: amplifying the voices of the victims.","authors":"The Lancet Haematology","doi":"10.1016/S2352-3026(24)00181-9","DOIUrl":"10.1016/S2352-3026(24)00181-9","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e471"},"PeriodicalIF":15.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301893","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 : 2024-06-01Epub Date: 2024-05-03DOI: 10.1016/S2352-3026(24)00081-4
Timothy J Craig, Donald S Levy, Avner Reshef, William R Lumry, Inmaculada Martinez-Saguer, Joshua S Jacobs, William H Yang, Bruce Ritchie, Emel Aygören-Pürsün, Paul K Keith, Paula Busse, Henrike Feuersenger, Mihai Alexandru Bica, Iris Jacobs, Ingo Pragst, Markus Magerl
<p><strong>Background: </strong>Garadacimab is a fully human immunoglobulin G4 monoclonal antibody targeting activated factor XII. This study evaluated long-term efficacy, health-related quality of life (HRQoL), and safety data for garadacimab in adults with hereditary angioedema.</p><p><strong>Methods: </strong>This global phase 2 study comprised a treatment period 1 (TP1: 12 weeks, double-blind, placebo-controlled) and a treatment period 2 (TP2: ≥44-week open-label extension). Patients aged 18-65 years with clinically confirmed hereditary angioedema were eligible. In TP1, 32 patients were randomly assigned (1:1:1:1) to receive subcutaneous garadacimab (75 mg, 200 mg, or 600 mg) or placebo every 4 weeks (once monthly). Randomisation was done using interactive response technology via block randomisation (block sizes 1-4). Subsequently, six additional patients in TP1 were assigned to open-label garadacimab 400 mg every 2 weeks. At the start of TP2, patients were re-randomised (if receiving placebo, garadacimab 75 mg, or garadacimab 400 mg) or continued to receive garadacimab 200 mg or garadacimab 600 mg once monthly. After a protocol amendment on March 20, 2020, patients originally assigned to the 600 mg dose were down-titrated to 200 mg at their next visit. The primary endpoint (published previously) was monthly attack rate for patients receiving 200 mg or 600 mg garadacimab in TP1 in the intention-to-treat population. Here, we assessed the impact of garadacimab on patient-reported and investigator-reported outcomes and HRQoL as well as long-term efficacy and safety. This trial is registered with ClinicalTrials.gov, NCT03712228, and is completed.</p><p><strong>Findings: </strong>Of 54 patients screened between Oct 29, 2018, and Aug 28, 2019, 32 randomised and six open-label patients completed TP1 and entered TP2 (20 in the garadacimab 200 mg group; 18 in the garadacimab 600 mg group; total 38 patients). Median age was 39·0 years (IQR 27·0-53·0), and 21 patients (55%) were female and 17 (45%) were male. In TP2, the median garadacimab exposure was 87·9 weeks (IQR 50·0-106·6) in the garadacimab 200 mg group and 44·1 weeks (24·1-56·1) in the garadacimab 600 mg group. Median monthly attack rates were 0·0 (IQR 0·0-0·1) in the garadacimab 200 mg group and 0·1 (0·0-0·4) in the garadacimb 600 mg group. Median reduction in monthly attack rate versus run-in was 100% (IQR 98-100) with garadacimab 200 mg. HRQoL improvements observed during TP1 with garadacimab were sustained throughout TP2. TP2 safety signals were consistent with TP1. Two patients experienced serious adverse events of diverticular perforation and asthma (not garadacimab-related). Treatment-emergent adverse events were mostly mild or moderate in severity. The most common adverse events were headache (nine of 38, 24%) and abdominal pain (seven of 38, 18%). There were no treatment-related deaths.</p><p><strong>Interpretation: </strong>Once-monthly garadacimab for more than 2 years in patients wi
{"title":"Garadacimab for hereditary angioedema attack prevention: long-term efficacy, quality of life, and safety data from a phase 2, randomised, open-label extension study.","authors":"Timothy J Craig, Donald S Levy, Avner Reshef, William R Lumry, Inmaculada Martinez-Saguer, Joshua S Jacobs, William H Yang, Bruce Ritchie, Emel Aygören-Pürsün, Paul K Keith, Paula Busse, Henrike Feuersenger, Mihai Alexandru Bica, Iris Jacobs, Ingo Pragst, Markus Magerl","doi":"10.1016/S2352-3026(24)00081-4","DOIUrl":"10.1016/S2352-3026(24)00081-4","url":null,"abstract":"<p><strong>Background: </strong>Garadacimab is a fully human immunoglobulin G4 monoclonal antibody targeting activated factor XII. This study evaluated long-term efficacy, health-related quality of life (HRQoL), and safety data for garadacimab in adults with hereditary angioedema.</p><p><strong>Methods: </strong>This global phase 2 study comprised a treatment period 1 (TP1: 12 weeks, double-blind, placebo-controlled) and a treatment period 2 (TP2: ≥44-week open-label extension). Patients aged 18-65 years with clinically confirmed hereditary angioedema were eligible. In TP1, 32 patients were randomly assigned (1:1:1:1) to receive subcutaneous garadacimab (75 mg, 200 mg, or 600 mg) or placebo every 4 weeks (once monthly). Randomisation was done using interactive response technology via block randomisation (block sizes 1-4). Subsequently, six additional patients in TP1 were assigned to open-label garadacimab 400 mg every 2 weeks. At the start of TP2, patients were re-randomised (if receiving placebo, garadacimab 75 mg, or garadacimab 400 mg) or continued to receive garadacimab 200 mg or garadacimab 600 mg once monthly. After a protocol amendment on March 20, 2020, patients originally assigned to the 600 mg dose were down-titrated to 200 mg at their next visit. The primary endpoint (published previously) was monthly attack rate for patients receiving 200 mg or 600 mg garadacimab in TP1 in the intention-to-treat population. Here, we assessed the impact of garadacimab on patient-reported and investigator-reported outcomes and HRQoL as well as long-term efficacy and safety. This trial is registered with ClinicalTrials.gov, NCT03712228, and is completed.</p><p><strong>Findings: </strong>Of 54 patients screened between Oct 29, 2018, and Aug 28, 2019, 32 randomised and six open-label patients completed TP1 and entered TP2 (20 in the garadacimab 200 mg group; 18 in the garadacimab 600 mg group; total 38 patients). Median age was 39·0 years (IQR 27·0-53·0), and 21 patients (55%) were female and 17 (45%) were male. In TP2, the median garadacimab exposure was 87·9 weeks (IQR 50·0-106·6) in the garadacimab 200 mg group and 44·1 weeks (24·1-56·1) in the garadacimab 600 mg group. Median monthly attack rates were 0·0 (IQR 0·0-0·1) in the garadacimab 200 mg group and 0·1 (0·0-0·4) in the garadacimb 600 mg group. Median reduction in monthly attack rate versus run-in was 100% (IQR 98-100) with garadacimab 200 mg. HRQoL improvements observed during TP1 with garadacimab were sustained throughout TP2. TP2 safety signals were consistent with TP1. Two patients experienced serious adverse events of diverticular perforation and asthma (not garadacimab-related). Treatment-emergent adverse events were mostly mild or moderate in severity. The most common adverse events were headache (nine of 38, 24%) and abdominal pain (seven of 38, 18%). There were no treatment-related deaths.</p><p><strong>Interpretation: </strong>Once-monthly garadacimab for more than 2 years in patients wi","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e436-e447"},"PeriodicalIF":15.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870113","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 : 2024-06-01DOI: 10.1016/S2352-3026(24)00102-9
Jehan Dupuis, Emmanuel Bachy, Franck Morschhauser, Guillaume Cartron, Noriko Fukuhara, Nicolas Daguindau, René-Olivier Casasnovas, Sylvia Snauwaert, Remy Gressin, Christopher P Fox, Francesco Annibale d'Amore, Philipp B Staber, Olivier Tournilhac, Krimo Bouabdallah, Catherine Thieblemont, Marc André, Shinya Rai, Daisuke Ennishi, Argyrios Gkasiamis, Mitsufumi Nishio, Luc-Matthieu Fornecker, Marie-Helene Delfau-Larue, Nouhoum Sako, Sebastien Mule, Laurence de Leval, Philippe Gaulard, Kunihiro Tsukasaki, François Lemonnier
<p><strong>Background: </strong>Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL.</p><p><strong>Methods: </strong>Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375).</p><p><strong>Findings: </strong>86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown).</p><p><strong>Interpretation: </strong>Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial.</p><
{"title":"Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study.","authors":"Jehan Dupuis, Emmanuel Bachy, Franck Morschhauser, Guillaume Cartron, Noriko Fukuhara, Nicolas Daguindau, René-Olivier Casasnovas, Sylvia Snauwaert, Remy Gressin, Christopher P Fox, Francesco Annibale d'Amore, Philipp B Staber, Olivier Tournilhac, Krimo Bouabdallah, Catherine Thieblemont, Marc André, Shinya Rai, Daisuke Ennishi, Argyrios Gkasiamis, Mitsufumi Nishio, Luc-Matthieu Fornecker, Marie-Helene Delfau-Larue, Nouhoum Sako, Sebastien Mule, Laurence de Leval, Philippe Gaulard, Kunihiro Tsukasaki, François Lemonnier","doi":"10.1016/S2352-3026(24)00102-9","DOIUrl":"10.1016/S2352-3026(24)00102-9","url":null,"abstract":"<p><strong>Background: </strong>Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL.</p><p><strong>Methods: </strong>Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375).</p><p><strong>Findings: </strong>86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown).</p><p><strong>Interpretation: </strong>Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial.</p><","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 6","pages":"e406-e414"},"PeriodicalIF":15.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155820","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 : 2024-06-01Epub Date: 2024-05-03DOI: 10.1016/S2352-3026(24)00140-6
Yaiza Del Pozo Martín
{"title":"50th Annual Meeting of the EBMT.","authors":"Yaiza Del Pozo Martín","doi":"10.1016/S2352-3026(24)00140-6","DOIUrl":"10.1016/S2352-3026(24)00140-6","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e400-e401"},"PeriodicalIF":24.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868522","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 : 2024-06-01Epub Date: 2024-04-30DOI: 10.1016/S2352-3026(24)00096-6
Najibah A Galadanci, Julie Kanter
{"title":"Long-term data from the REACH study testing hydroxyurea to treat sickle cell anaemia in children in sub-Saharan Africa.","authors":"Najibah A Galadanci, Julie Kanter","doi":"10.1016/S2352-3026(24)00096-6","DOIUrl":"10.1016/S2352-3026(24)00096-6","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e393-e395"},"PeriodicalIF":24.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874960","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 : 2024-06-01DOI: 10.1016/S2352-3026(24)00145-5
The Lancet Haematology
{"title":"Long term strategies for individuals with sickle cell disease.","authors":"The Lancet Haematology","doi":"10.1016/S2352-3026(24)00145-5","DOIUrl":"10.1016/S2352-3026(24)00145-5","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 6","pages":"e391"},"PeriodicalIF":24.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155819","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 : 2024-06-01DOI: 10.1016/S2352-3026(24)00110-8
Francesca Granata, Rayan Bou-Fakhredin, Maria Domenica Cappellini, Irene Motta
{"title":"Step out of the shadows: a call for action for rare diseases.","authors":"Francesca Granata, Rayan Bou-Fakhredin, Maria Domenica Cappellini, Irene Motta","doi":"10.1016/S2352-3026(24)00110-8","DOIUrl":"10.1016/S2352-3026(24)00110-8","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"11 6","pages":"e403"},"PeriodicalIF":24.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155823","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 : 2024-06-01Epub Date: 2024-05-08DOI: 10.1016/S2352-3026(24)00077-2
Kai Rejeski, Michael D Jain, Nirali N Shah, Miguel-Angel Perales, Marion Subklewe
Genetically engineered chimeric antigen receptor (CAR) T cells have become an effective treatment option for several advanced B-cell malignancies. Haematological side-effects, classified in 2023 as immune effector cell-associated haematotoxicity (ICAHT), are very common and can predispose for clinically relevant infections. As haematopoietic reconstitution after CAR T-cell therapy differs from chemotherapy-associated myelosuppression, a novel classification system for early and late ICAHT has been introduced. Furthermore, a risk stratification score named CAR-HEMATOTOX has been developed to identify candidates at high risk of ICAHT, thereby enabling risk-based interventional strategies. Therapeutically, growth factor support with granulocyte colony-stimulating factor (G-CSF) is the mainstay of treatment, with haematopoietic stem cell (HSC) boosts available for patients who are refractory to G-CSF (if available). Although the underlying pathophysiology remains poorly understood, translational studies from the past 3 years suggest that CAR T-cell-induced inflammation and baseline haematopoietic function are key contributors to prolonged cytopenia. In this Review, we provide an overview of the spectrum of haematological toxicities after CAR T-cell therapy and offer perspectives on future translational and clinical developments.
基因工程嵌合抗原受体（CAR）T 细胞已成为治疗多种晚期 B 细胞恶性肿瘤的有效方法。血液学副作用在2023年被归类为免疫效应细胞相关血液毒性（ICAHT），这种副作用非常常见，并可能导致临床相关感染。由于 CAR T 细胞疗法后的造血重建不同于化疗相关的骨髓抑制，因此引入了一种新的早期和晚期 ICAHT 分类系统。此外，还开发了一种名为 CAR-HEMATOTOX 的风险分层评分，用于识别 ICAHT 高风险候选者，从而制定基于风险的干预策略。在治疗上，使用粒细胞集落刺激因子（G-CSF）支持生长因子是主要的治疗方法，对G-CSF难治的患者（如果有的话）可以使用造血干细胞（HSC）促进疗法。虽然人们对潜在的病理生理学仍知之甚少，但过去三年的转化研究表明，CAR T 细胞诱导的炎症和基线造血功能是导致全血细胞减少症延长的关键因素。在本综述中，我们将概述 CAR T 细胞疗法后的血液学毒性，并对未来的转化和临床发展提出展望。
{"title":"Immune effector cell-associated haematotoxicity after CAR T-cell therapy: from mechanism to management.","authors":"Kai Rejeski, Michael D Jain, Nirali N Shah, Miguel-Angel Perales, Marion Subklewe","doi":"10.1016/S2352-3026(24)00077-2","DOIUrl":"10.1016/S2352-3026(24)00077-2","url":null,"abstract":"<p><p>Genetically engineered chimeric antigen receptor (CAR) T cells have become an effective treatment option for several advanced B-cell malignancies. Haematological side-effects, classified in 2023 as immune effector cell-associated haematotoxicity (ICAHT), are very common and can predispose for clinically relevant infections. As haematopoietic reconstitution after CAR T-cell therapy differs from chemotherapy-associated myelosuppression, a novel classification system for early and late ICAHT has been introduced. Furthermore, a risk stratification score named CAR-HEMATOTOX has been developed to identify candidates at high risk of ICAHT, thereby enabling risk-based interventional strategies. Therapeutically, growth factor support with granulocyte colony-stimulating factor (G-CSF) is the mainstay of treatment, with haematopoietic stem cell (HSC) boosts available for patients who are refractory to G-CSF (if available). Although the underlying pathophysiology remains poorly understood, translational studies from the past 3 years suggest that CAR T-cell-induced inflammation and baseline haematopoietic function are key contributors to prolonged cytopenia. In this Review, we provide an overview of the spectrum of haematological toxicities after CAR T-cell therapy and offer perspectives on future translational and clinical developments.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":"e459-e470"},"PeriodicalIF":24.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909681","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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