Pub Date : 2025-02-04DOI: 10.1016/S2352-3026(24)00372-7
Sijian Yu, Fen Huang, Na Xu, Zhongming Zhang, Can Liu, Xiaojun Xu, Zhiping Fan, Xiangzong Zeng, Qiong Liu, Guo Qiu, Xu Xi, Ren Lin, Xinquan Liang, Yirong Jiang, Min Dai, Hua Jin, Xiaofang Li, Shunqing Wang, Meiqing Wu, Jing Sun, Li Xuan, Qifa Liu
<p><strong>Background: </strong>Retrospective studies suggested that haploidentical transplantation combined with unrelated cord blood might improve survival for patients with haematological malignancies. We aimed to assess whether transplantation of haploidentical peripheral blood stem cells (PBSCs) plus unrelated cord blood would achieve superior disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in this population.</p><p><strong>Methods: </strong>We did an open-label, randomised, phase 3 trial at seven hospitals in China. Eligible patients (aged 18-65 years) had a diagnosis of haematological malignancy, an Eastern Cooperative Oncology Group performance status of 0-2 and transplant comorbidity index of 0-2, and were receiving their first allogenic haematopoietic stem cell transplant. Patients were randomly assigned (1:1) to receive transplantation of haploidentical PBSCs plus bone marrow or haploidentical PBSCs plus unrelated cord blood. The primary endpoint was 1-year disease-free survival. All efficacy and safety endpoints were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT05290545) and is complete.</p><p><strong>Findings: </strong>Between March 5, 2022, and Jan 2, 2023, 357 participants were screened for eligibility, and 314 were randomly assigned to receive transplantation of haploidentical PBSCs plus unrelated cord blood (n=157) or haploidentical PBSCs plus bone marrow (n=157). Median follow-up was 17·2 months (IQR 10·0-20·8) after random assignment. 1-year disease-free survival was 82·2% (95% CI 75·2-87·3) in the group receiving haploidentical PBSCs plus unrelated cord blood (PBSCs plus unrelated cord blood group) and 65·6% (57·6-72·5) in the group receiving haploidentical PBSCs plus bone marrow ([PBSCs plus bone marrow group] hazard ratio [HR] 0·47, 95% CI 0·30-0·74; p=0·0010). The most common grade 3-5 adverse events within 100 days of transplantation in participants in the PBSCs plus unrelated cord blood and PBSCs plus bone marrow groups were infections (58 [37%] of 157 vs 77 [49%] of 157, p=0·030), acute graft-versus-host disease (49 [31%] vs 61 [39%]), and gastrointestinal disorders (38 [24%] vs 38 [24%]). Seven (4%) patients in the PBSCs plus unrelated cord blood group and 17 (11%) in the PBSCs plus bone marrow group died of transplantation-related causes within 100 days of transplantation. Causes of deaths in the PBSCs plus unrelated cord blood group versus the PBSCs plus bone marrow group included infections (four [3%] vs 11 [7%]), acute graft-versus-host disease (one [1%] vs three [2%]), vascular disorders (two [1%] vs one [1%]), cardiac disorders (none vs one [1%]), and respiratory disorders (none vs one [1%]).</p><p><strong>Interpretation: </strong>Transplantation of haploidentical PBSCs plus unrelated cord blood achieved superior 1-year disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in p
{"title":"Haploidentical peripheral blood stem cells combined with bone marrow or unrelated cord blood as grafts for haematological malignancies: an open-label, multicentre, randomised, phase 3 trial.","authors":"Sijian Yu, Fen Huang, Na Xu, Zhongming Zhang, Can Liu, Xiaojun Xu, Zhiping Fan, Xiangzong Zeng, Qiong Liu, Guo Qiu, Xu Xi, Ren Lin, Xinquan Liang, Yirong Jiang, Min Dai, Hua Jin, Xiaofang Li, Shunqing Wang, Meiqing Wu, Jing Sun, Li Xuan, Qifa Liu","doi":"10.1016/S2352-3026(24)00372-7","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00372-7","url":null,"abstract":"<p><strong>Background: </strong>Retrospective studies suggested that haploidentical transplantation combined with unrelated cord blood might improve survival for patients with haematological malignancies. We aimed to assess whether transplantation of haploidentical peripheral blood stem cells (PBSCs) plus unrelated cord blood would achieve superior disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in this population.</p><p><strong>Methods: </strong>We did an open-label, randomised, phase 3 trial at seven hospitals in China. Eligible patients (aged 18-65 years) had a diagnosis of haematological malignancy, an Eastern Cooperative Oncology Group performance status of 0-2 and transplant comorbidity index of 0-2, and were receiving their first allogenic haematopoietic stem cell transplant. Patients were randomly assigned (1:1) to receive transplantation of haploidentical PBSCs plus bone marrow or haploidentical PBSCs plus unrelated cord blood. The primary endpoint was 1-year disease-free survival. All efficacy and safety endpoints were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT05290545) and is complete.</p><p><strong>Findings: </strong>Between March 5, 2022, and Jan 2, 2023, 357 participants were screened for eligibility, and 314 were randomly assigned to receive transplantation of haploidentical PBSCs plus unrelated cord blood (n=157) or haploidentical PBSCs plus bone marrow (n=157). Median follow-up was 17·2 months (IQR 10·0-20·8) after random assignment. 1-year disease-free survival was 82·2% (95% CI 75·2-87·3) in the group receiving haploidentical PBSCs plus unrelated cord blood (PBSCs plus unrelated cord blood group) and 65·6% (57·6-72·5) in the group receiving haploidentical PBSCs plus bone marrow ([PBSCs plus bone marrow group] hazard ratio [HR] 0·47, 95% CI 0·30-0·74; p=0·0010). The most common grade 3-5 adverse events within 100 days of transplantation in participants in the PBSCs plus unrelated cord blood and PBSCs plus bone marrow groups were infections (58 [37%] of 157 vs 77 [49%] of 157, p=0·030), acute graft-versus-host disease (49 [31%] vs 61 [39%]), and gastrointestinal disorders (38 [24%] vs 38 [24%]). Seven (4%) patients in the PBSCs plus unrelated cord blood group and 17 (11%) in the PBSCs plus bone marrow group died of transplantation-related causes within 100 days of transplantation. Causes of deaths in the PBSCs plus unrelated cord blood group versus the PBSCs plus bone marrow group included infections (four [3%] vs 11 [7%]), acute graft-versus-host disease (one [1%] vs three [2%]), vascular disorders (two [1%] vs one [1%]), cardiac disorders (none vs one [1%]), and respiratory disorders (none vs one [1%]).</p><p><strong>Interpretation: </strong>Transplantation of haploidentical PBSCs plus unrelated cord blood achieved superior 1-year disease-free survival compared with transplantation of haploidentical PBSCs plus bone marrow in p","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":" ","pages":""},"PeriodicalIF":15.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371178","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 : 2025-02-01DOI: 10.1016/S2352-3026(24)00278-3
David C Fajgenbaum, Sally Nijim, Grant Mitchell, Matej Macak, Chris Bizon, Alexander Tropsha, David Koslicki
{"title":"Pioneering a new field of computational pharmacophenomics to unlock the life-saving potential of existing medicines.","authors":"David C Fajgenbaum, Sally Nijim, Grant Mitchell, Matej Macak, Chris Bizon, Alexander Tropsha, David Koslicki","doi":"10.1016/S2352-3026(24)00278-3","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00278-3","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 2","pages":"e94-e96"},"PeriodicalIF":15.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256971","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 : 2025-02-01DOI: 10.1016/S2352-3026(24)00355-7
Pasquale Niscola
{"title":"Improved survival and enhanced quality of life through anaemia correction in lower risk myelodysplastic syndromes: meaningful insights from an EUMDS Registry study.","authors":"Pasquale Niscola","doi":"10.1016/S2352-3026(24)00355-7","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00355-7","url":null,"abstract":"","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 2","pages":"e88-e90"},"PeriodicalIF":15.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256964","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 : 2025-02-01Epub Date: 2025-01-03DOI: 10.1016/S2352-3026(24)00309-0
Georgia Mills, Antonia Shand, Debra Kennedy, Sandra Lowe, Victoria Bilsland, Briony Cutts, Bruce McBride, Wendy Brown, Srinivas Bolisetty, Eva A Wegner, Giselle Kidson-Gerber
Haematological malignancies affect 12·5 in 100 000 pregnancies. Over the past two decades, the number of haematological malignancies in pregnancy has substantially increased. Life-threatening haematological malignancies in pregnancy, such as acute leukaemia and aggressive lymphomas, pose a unique therapeutic challenge: clinicians must consider both maternal and fetal wellbeing, aiming to deliver optimal curative therapy for the patient and a successful pregnancy outcome. A multidisciplinary approach to disease management is paramount, and there are currently no clinical practice guidelines available. An Australasian working group, including representatives from haematology, obstetric medicine, clinical teratology, radiology, nuclear medicine, maternal-fetal medicine, and a patient representative, was established to develop this position statement, which is based on a combination of current evidence and expert consensus. We provide recommendations for diagnosis and staging, imaging safety in pregnancy, therapy in pregnancy incorporating a multidisciplinary approach, supportive care, oncofertility, and pregnancy and birth management. This Viewpoint was reviewed and endorsed by the councils of the Society of Obstetric Medicine of Australia and New Zealand, the Haematology Society of Australia and New Zealand, and the Haematology in Obstetric and Women's Health Collaborative.
{"title":"Position statement on the diagnosis and management of acute leukaemia and aggressive lymphomas in pregnancy.","authors":"Georgia Mills, Antonia Shand, Debra Kennedy, Sandra Lowe, Victoria Bilsland, Briony Cutts, Bruce McBride, Wendy Brown, Srinivas Bolisetty, Eva A Wegner, Giselle Kidson-Gerber","doi":"10.1016/S2352-3026(24)00309-0","DOIUrl":"10.1016/S2352-3026(24)00309-0","url":null,"abstract":"<p><p>Haematological malignancies affect 12·5 in 100 000 pregnancies. Over the past two decades, the number of haematological malignancies in pregnancy has substantially increased. Life-threatening haematological malignancies in pregnancy, such as acute leukaemia and aggressive lymphomas, pose a unique therapeutic challenge: clinicians must consider both maternal and fetal wellbeing, aiming to deliver optimal curative therapy for the patient and a successful pregnancy outcome. A multidisciplinary approach to disease management is paramount, and there are currently no clinical practice guidelines available. An Australasian working group, including representatives from haematology, obstetric medicine, clinical teratology, radiology, nuclear medicine, maternal-fetal medicine, and a patient representative, was established to develop this position statement, which is based on a combination of current evidence and expert consensus. We provide recommendations for diagnosis and staging, imaging safety in pregnancy, therapy in pregnancy incorporating a multidisciplinary approach, supportive care, oncofertility, and pregnancy and birth management. This Viewpoint was reviewed and endorsed by the councils of the Society of Obstetric Medicine of Australia and New Zealand, the Haematology Society of Australia and New Zealand, and the Haematology in Obstetric and Women's Health Collaborative.</p>","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 2","pages":"e151-e162"},"PeriodicalIF":15.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256972","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 : 2025-02-01DOI: 10.1016/S2352-3026(24)00347-8
Frida Bugge Askeland, Einar Haukås, Tobias S Slørdahl, Anja Klostergaard, Tatjana Alexandersen, Anna Lysén, Pegah Abdollahi, Lene Kongsgaard Nielsen, Emil Hermansen, Fredrik Schjesvold
<p><strong>Background: </strong>Adding anti-CD38 monoclonal antibodies to standard therapies can improve outcomes in patients with multiple myeloma. Long-term treatment with corticosteroids increases the risk of infection. We aimed to evaluate the safety and activity of isatuximab, weekly bortezomib, lenalidomide, and limited dexamethasone in patients with newly diagnosed multiple myeloma ineligible for autologous haematopoietic stem-cell transplantation (HSCT).</p><p><strong>Methods: </strong>REST is an academic, multicentre, single-arm, phase 2 trial of adults with newly diagnosed multiple myeloma and measurable disease as defined by International Myeloma Working Group criteria, ineligible for high-dose melphalan and autologous HSCT, Eastern Cooperative Oncology Group performance status of 0-3 (with 3 only allowed if related to myeloma). In 28-day cycles, patients received isatuximab (10 mg/kg intravenously on days 1, 8, 15, and 22 of cycle 1, and days 1 and 15 of cycles 2-18), bortezomib (1·3 mg/m<sup>2</sup> subcutaneously on days 1, 8, and 15 of cycles 1-8), and lenalidomide (25 mg orally on days 1-21, until progressive disease). Dexamethasone was given 20 mg orally on days 1, 8, 15 and 22, limited to the two first cycles only. The primary endpoint was measurable residual disease (MRD)-negative complete response, assessed by next-generation flow cytometry (sensitivity 1·0 × 10<sup>-5</sup>), during or after 18 cycles of study treatment. MRD was tested in all patients who had at least complete response before cycle 19 and in all patients who had at least very good partial response at cycle 19. All patients enrolled initiated treatment and were included in the analyses. This trial is registered with ClinicalTrials.gov (NCT04939844); the primary endpoint is reported in this Article, and follow-up is ongoing.</p><p><strong>Findings: </strong>Between June 30, 2021 and Jan 19, 2023, we assessed for eligibility and recruited 51 patients (27 [53%] females and 24 [47%] males), with a median age of 77 years (IQR 73·5-80). 39 participants completed 18 cycles of treatment on protocol, of whom two had discontinued treatment but not protocol. At a median follow-up of 27·0 months (IQR 23·0-33·7), MRD-negative complete response was observed in 19 (37% [95% CI 25·3-51·0]) patients, with a median treatment duration of 22 months (IQR 15·2-28·8; range 1·4-35·1). Disease progression or death had occurred in 18 (35%) of 51 patients, and eight (16%) patients had died. During the first 18 cycles of study treatment, the most common adverse events of grade 3 or 4 were neutropenia (28 [55%] patients), infections (21 [41%] patients), and thrombocytopenia (11 [22%] patients). 48 serious adverse events of grade 3 or higher were reported in 27 (53%) patients. A total of 14 (27%) patients discontinued treatment before cycle 19, most commonly because of progressive disease (eight [16%]) and adverse events (four [8%]). Two deaths (one due to pneumonia and one due to sepsis)
{"title":"Isatuximab, bortezomib, lenalidomide, and limited dexamethasone in patients with transplant-ineligible multiple myeloma (REST): a multicentre, single-arm, phase 2 trial.","authors":"Frida Bugge Askeland, Einar Haukås, Tobias S Slørdahl, Anja Klostergaard, Tatjana Alexandersen, Anna Lysén, Pegah Abdollahi, Lene Kongsgaard Nielsen, Emil Hermansen, Fredrik Schjesvold","doi":"10.1016/S2352-3026(24)00347-8","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00347-8","url":null,"abstract":"<p><strong>Background: </strong>Adding anti-CD38 monoclonal antibodies to standard therapies can improve outcomes in patients with multiple myeloma. Long-term treatment with corticosteroids increases the risk of infection. We aimed to evaluate the safety and activity of isatuximab, weekly bortezomib, lenalidomide, and limited dexamethasone in patients with newly diagnosed multiple myeloma ineligible for autologous haematopoietic stem-cell transplantation (HSCT).</p><p><strong>Methods: </strong>REST is an academic, multicentre, single-arm, phase 2 trial of adults with newly diagnosed multiple myeloma and measurable disease as defined by International Myeloma Working Group criteria, ineligible for high-dose melphalan and autologous HSCT, Eastern Cooperative Oncology Group performance status of 0-3 (with 3 only allowed if related to myeloma). In 28-day cycles, patients received isatuximab (10 mg/kg intravenously on days 1, 8, 15, and 22 of cycle 1, and days 1 and 15 of cycles 2-18), bortezomib (1·3 mg/m<sup>2</sup> subcutaneously on days 1, 8, and 15 of cycles 1-8), and lenalidomide (25 mg orally on days 1-21, until progressive disease). Dexamethasone was given 20 mg orally on days 1, 8, 15 and 22, limited to the two first cycles only. The primary endpoint was measurable residual disease (MRD)-negative complete response, assessed by next-generation flow cytometry (sensitivity 1·0 × 10<sup>-5</sup>), during or after 18 cycles of study treatment. MRD was tested in all patients who had at least complete response before cycle 19 and in all patients who had at least very good partial response at cycle 19. All patients enrolled initiated treatment and were included in the analyses. This trial is registered with ClinicalTrials.gov (NCT04939844); the primary endpoint is reported in this Article, and follow-up is ongoing.</p><p><strong>Findings: </strong>Between June 30, 2021 and Jan 19, 2023, we assessed for eligibility and recruited 51 patients (27 [53%] females and 24 [47%] males), with a median age of 77 years (IQR 73·5-80). 39 participants completed 18 cycles of treatment on protocol, of whom two had discontinued treatment but not protocol. At a median follow-up of 27·0 months (IQR 23·0-33·7), MRD-negative complete response was observed in 19 (37% [95% CI 25·3-51·0]) patients, with a median treatment duration of 22 months (IQR 15·2-28·8; range 1·4-35·1). Disease progression or death had occurred in 18 (35%) of 51 patients, and eight (16%) patients had died. During the first 18 cycles of study treatment, the most common adverse events of grade 3 or 4 were neutropenia (28 [55%] patients), infections (21 [41%] patients), and thrombocytopenia (11 [22%] patients). 48 serious adverse events of grade 3 or higher were reported in 27 (53%) patients. A total of 14 (27%) patients discontinued treatment before cycle 19, most commonly because of progressive disease (eight [16%]) and adverse events (four [8%]). Two deaths (one due to pneumonia and one due to sepsis) ","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 2","pages":"e120-e127"},"PeriodicalIF":15.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256967","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 : 2025-02-01DOI: 10.1016/S2352-3026(24)00350-8
Hege Kristin Gravdahl Garelius, Timothy Bagguley, Adele Taylor, Pierre Fenaux, David Bowen, Argiris Symeonidis, Moshe Mittelmann, Reinhard Stauder, Jaroslav Čermák, Guillermo Sanz, Saskia Langemeijer, Luca Malcovati, Ulrich Germing, Laurence Sanhes, Maud d'Aveni, Dominic Culligan, Ioannis Kotsianidis, Karin A Koinig, Corine van Marrewijk, Simon Crouch, Theo deWitte, Alexandra Smith, Eva Hellström-Lindberg
<p><strong>Background: </strong>In our previous study on erythropoiesis-stimulating agent (ESA) treatment in lower risk myelodysplastic syndromes from the European MDS (EUMDS) Registry, we showed that patients treated with ESAs had longer survival compared with patients who receive red blood cell transfusion (RBCT). In this study, with a longer follow up time and more patients included, we aimed to assess long-term effects on survival and health-related quality of life (HRQoL) of exposure to ESAs with or without RBCT in patients with lower risk myelodysplastic syndromes.</p><p><strong>Methods: </strong>The EUMDS Registry is a non-interventional, longitudinal, real-world registry prospectively enrolling newly diagnosed patients older than 18 years with lower risk (International Prognostic Scoring System low or intermediate-1) myelodysplastic syndromes from 16 European countries and Israel. The analysis was restricted to patients with haemoglobin concentrations less than 100 g/L enrolled between Jan 1, 2008, and July 1, 2019, with last censoring of data on Dec 31, 2021. Patient management was recorded every 6 months, including treatment, transfusions, and HRQoL. ESA treatment followed local guidelines. The patients were separated into four groups at each study visit: no ESA or RBCT, ESA only, ESA plus RBCT, and RBCT only. The data were analysed longitudinally over time according to ESA and RBCT status during each 6-month interval, using propensity score matching. The main outcomes were median overall survival and leukaemia-free survival, and HRQoL. This study is registered with ClinicalTrials.gov, NCT00600860, as is ongoing.</p><p><strong>Findings: </strong>2448 patients (the ESA-unexposed group [n=1265] and ESA-exposed group [n=1183]) were diagnosed before July 1, 2019; 1520 (62·1%) were male and 928 (37·9%) were female. Median follow-up time was 3·9 years (IQR 1·6-6·5). After applying eligibility criteria and propensity matching, there were 426 patients in the ESA-unexposed group and 744 patients in the ESA-exposed group. Median overall survival in the ESA exposed group was 44·9 months (95% CI 40·2-50·5) compared with 34·8 months (28·6-39·2) in the ESA unexposed group; the absolute difference was 10·1 months (95% CI 2·2-18·0; hazard ratio [HR] 0·70 [95% CI 0·59-0·83]; p<0·0001). Patients without RBCT in the presence or absence of ESA exposure maintained significantly better HRQoL than those with RBCT, irrespective of ESA exposure (linear mixed effect model of EQ-5d-3L index score, RBCT coefficient -0·04 [95% CI -0·06 to 0·03], p<0·0001; linear mixed effect model of VAS, -4·57 [-6·02 to -3·13], p<0·0001).</p><p><strong>Interpretation: </strong>ESA treatment in patients with lower risk myelodysplastic syndromes significantly improves overall survival when started before or early after the onset of regular transfusion therapy. Avoiding RBCT is associated with significantly better HRQoL.</p><p><strong>Funding: </strong>H2020 European Research Council
{"title":"Survival and quality of life in patients with lower risk myelodysplastic syndromes exposed to erythropoiesis-stimulating agents: an observational cohort study.","authors":"Hege Kristin Gravdahl Garelius, Timothy Bagguley, Adele Taylor, Pierre Fenaux, David Bowen, Argiris Symeonidis, Moshe Mittelmann, Reinhard Stauder, Jaroslav Čermák, Guillermo Sanz, Saskia Langemeijer, Luca Malcovati, Ulrich Germing, Laurence Sanhes, Maud d'Aveni, Dominic Culligan, Ioannis Kotsianidis, Karin A Koinig, Corine van Marrewijk, Simon Crouch, Theo deWitte, Alexandra Smith, Eva Hellström-Lindberg","doi":"10.1016/S2352-3026(24)00350-8","DOIUrl":"https://doi.org/10.1016/S2352-3026(24)00350-8","url":null,"abstract":"<p><strong>Background: </strong>In our previous study on erythropoiesis-stimulating agent (ESA) treatment in lower risk myelodysplastic syndromes from the European MDS (EUMDS) Registry, we showed that patients treated with ESAs had longer survival compared with patients who receive red blood cell transfusion (RBCT). In this study, with a longer follow up time and more patients included, we aimed to assess long-term effects on survival and health-related quality of life (HRQoL) of exposure to ESAs with or without RBCT in patients with lower risk myelodysplastic syndromes.</p><p><strong>Methods: </strong>The EUMDS Registry is a non-interventional, longitudinal, real-world registry prospectively enrolling newly diagnosed patients older than 18 years with lower risk (International Prognostic Scoring System low or intermediate-1) myelodysplastic syndromes from 16 European countries and Israel. The analysis was restricted to patients with haemoglobin concentrations less than 100 g/L enrolled between Jan 1, 2008, and July 1, 2019, with last censoring of data on Dec 31, 2021. Patient management was recorded every 6 months, including treatment, transfusions, and HRQoL. ESA treatment followed local guidelines. The patients were separated into four groups at each study visit: no ESA or RBCT, ESA only, ESA plus RBCT, and RBCT only. The data were analysed longitudinally over time according to ESA and RBCT status during each 6-month interval, using propensity score matching. The main outcomes were median overall survival and leukaemia-free survival, and HRQoL. This study is registered with ClinicalTrials.gov, NCT00600860, as is ongoing.</p><p><strong>Findings: </strong>2448 patients (the ESA-unexposed group [n=1265] and ESA-exposed group [n=1183]) were diagnosed before July 1, 2019; 1520 (62·1%) were male and 928 (37·9%) were female. Median follow-up time was 3·9 years (IQR 1·6-6·5). After applying eligibility criteria and propensity matching, there were 426 patients in the ESA-unexposed group and 744 patients in the ESA-exposed group. Median overall survival in the ESA exposed group was 44·9 months (95% CI 40·2-50·5) compared with 34·8 months (28·6-39·2) in the ESA unexposed group; the absolute difference was 10·1 months (95% CI 2·2-18·0; hazard ratio [HR] 0·70 [95% CI 0·59-0·83]; p<0·0001). Patients without RBCT in the presence or absence of ESA exposure maintained significantly better HRQoL than those with RBCT, irrespective of ESA exposure (linear mixed effect model of EQ-5d-3L index score, RBCT coefficient -0·04 [95% CI -0·06 to 0·03], p<0·0001; linear mixed effect model of VAS, -4·57 [-6·02 to -3·13], p<0·0001).</p><p><strong>Interpretation: </strong>ESA treatment in patients with lower risk myelodysplastic syndromes significantly improves overall survival when started before or early after the onset of regular transfusion therapy. Avoiding RBCT is associated with significantly better HRQoL.</p><p><strong>Funding: </strong>H2020 European Research Council","PeriodicalId":48726,"journal":{"name":"Lancet Haematology","volume":"12 2","pages":"e128-e137"},"PeriodicalIF":15.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256973","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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