Pub Date : 2024-08-08DOI: 10.3324/haematol.2024.285973
Laura K Hilton
Not available.
不详。
{"title":"A <i>nu</i> mouse model of diffuse large B-cell lymphoma in constitutional <i>Atm</i> loss.","authors":"Laura K Hilton","doi":"10.3324/haematol.2024.285973","DOIUrl":"https://doi.org/10.3324/haematol.2024.285973","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901560","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 : 2024-08-08DOI: 10.3324/haematol.2024.285233
Caroline S Myers, Eli Williams, Carlos Barrionuevo Cornejo, Georgios Pongas, Ngoc L Toomey, Jose A Sanches, Maxime Battistella, Samuel Mo, Melissa Pulitzer, Cristopher A Moskaluk, Govind Bhagat, Kenneth Ofori, Jonathan J Davick, Octavio Servitje, Denis Miyashiro, Fina Climent, Kimberley Ringbloom, Daniela Duenas, Calvin Law, Sandro Casavilca Zambrano, Luis Malpica, Brady E Beltran, Denisse Castro, Luciana Barreto, Carlos Brites, Jennifer R Chapman, Jaehyuk Choi, Alejandro A Gru, Juan C Ramos
Adult T-cell leukemia-lymphoma (ATLL) is an aggressive Human T-cell Leukemia Virus Type 1 (HTLV-1)-driven malignancy. Although Western hemisphere (Afro-Caribbean and South American) patients face worse prognoses, our understanding of ATLL molecular drivers derives mostly from Japanese studies. We performed multi-omic analyses to elucidate the genomic landscape of ATLL in Western cohorts. Recurrent deletion and/or damaging mutations involving FOXO3, ANKRD11, DGKZ, and PTPN6 implicate these genes as potential tumor suppressors. RNA-seq, published functional data and in vitro assays support the roles of ANKRD11 and FOXO3 as regulators of T-cell proliferation and apoptosis in ATLL, respectively. Survival data suggest ANKRD11 mutation may confer a worse prognosis. Japanese and Western cohorts, in addition to acute and lymphomatous subtypes, demonstrated distinct molecular patterns. GATA3 deletion was associated with unfavorable chronic cases. IRF4 and CARD11 mutations frequently emerged in relapses after interferon therapy. Our findings reveal novel putative ATLL driver genes and clinically relevant differences between Japanese and Western ATLL patients.
成人 T 细胞白血病淋巴瘤(ATLL)是一种侵袭性人类 T 细胞白血病病毒 1 型(HTLV-1)驱动的恶性肿瘤。虽然西半球(非洲-加勒比海和南美洲)患者的预后较差,但我们对 ATLL 分子驱动因素的了解主要来自日本的研究。我们进行了多组学分析,以阐明西方队列中 ATLL 的基因组状况。涉及 FOXO3、ANKRD11、DGKZ 和 PTPN6 的反复缺失和/或损伤性突变使这些基因成为潜在的肿瘤抑制因子。RNA-seq、已发表的功能数据和体外实验支持 ANKRD11 和 FOXO3 在 ATLL 中分别作为 T 细胞增殖和凋亡的调节因子。生存数据表明,ANKRD11突变可能会导致预后恶化。除了急性亚型和淋巴瘤亚型外,日本和西方队列也显示出不同的分子模式。GATA3缺失与不利的慢性病例有关。IRF4和CARD11突变经常出现在干扰素治疗后的复发病例中。我们的研究结果揭示了新的假定 ATLL 驱动基因,以及日本和西方 ATLL 患者在临床上的相关差异。
{"title":"Distinctive genomic features of human T-lymphotropic virus type 1-related adult T-cell leukemia-lymphoma in Western populations.","authors":"Caroline S Myers, Eli Williams, Carlos Barrionuevo Cornejo, Georgios Pongas, Ngoc L Toomey, Jose A Sanches, Maxime Battistella, Samuel Mo, Melissa Pulitzer, Cristopher A Moskaluk, Govind Bhagat, Kenneth Ofori, Jonathan J Davick, Octavio Servitje, Denis Miyashiro, Fina Climent, Kimberley Ringbloom, Daniela Duenas, Calvin Law, Sandro Casavilca Zambrano, Luis Malpica, Brady E Beltran, Denisse Castro, Luciana Barreto, Carlos Brites, Jennifer R Chapman, Jaehyuk Choi, Alejandro A Gru, Juan C Ramos","doi":"10.3324/haematol.2024.285233","DOIUrl":"https://doi.org/10.3324/haematol.2024.285233","url":null,"abstract":"<p><p>Adult T-cell leukemia-lymphoma (ATLL) is an aggressive Human T-cell Leukemia Virus Type 1 (HTLV-1)-driven malignancy. Although Western hemisphere (Afro-Caribbean and South American) patients face worse prognoses, our understanding of ATLL molecular drivers derives mostly from Japanese studies. We performed multi-omic analyses to elucidate the genomic landscape of ATLL in Western cohorts. Recurrent deletion and/or damaging mutations involving FOXO3, ANKRD11, DGKZ, and PTPN6 implicate these genes as potential tumor suppressors. RNA-seq, published functional data and in vitro assays support the roles of ANKRD11 and FOXO3 as regulators of T-cell proliferation and apoptosis in ATLL, respectively. Survival data suggest ANKRD11 mutation may confer a worse prognosis. Japanese and Western cohorts, in addition to acute and lymphomatous subtypes, demonstrated distinct molecular patterns. GATA3 deletion was associated with unfavorable chronic cases. IRF4 and CARD11 mutations frequently emerged in relapses after interferon therapy. Our findings reveal novel putative ATLL driver genes and clinically relevant differences between Japanese and Western ATLL patients.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901564","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 : 2024-08-08DOI: 10.3324/haematol.2024.285428
Kirsten A Thus, Hester A De Groot-Kruseman, Pauline Winkler-Seinstra, Marta Fiocco, Heidi Segers, Cor Van den Bos, Inge M Van der Sluis, Wim J E Tissing, Margreet A Veening, Christian Michel Zwaan, Cornelis M Van Tilburg, Rob Pieters, Marc Bierings
Infections lead to substantial morbidity during treatment of acute lymphoblastic leukemia (ALL) in which the adaptive immune system gets severely affected, leading to declining serum immunoglobulin levels. The aim of this trial was to investigate whether intravenous immunoglobulin (IVIG) prophylaxis in pediatric patients with ALL prevents admissions for fever. This randomized controlled trial was a subtrial of the national Dutch multicenter ALL study. Patients aged 1-19 years with medium risk (MR) ALL were randomized into two groups receiving either IVIG prophylaxis (0.7 g/kg IVIG given every three weeks, starting day 22 after diagnosis) or well defined standard of care (control group). Between October 2012 until March 2019, 91 (51%) patients were randomly assigned to IVIG prophylaxis and 86 (49%) to the control arm. In the IVIG prophylaxis group there were 206 admissions for fever versus 271 in the control group (p=0.011). IVIG prophylaxis was not associated with bacteremia. However, IVIG prophylaxis was associated with significantly less admissions for fever with negative blood cultures compared to the control group (N=113 versus 200, p.
在急性淋巴细胞白血病(ALL)的治疗过程中,感染会导致严重的发病率,其中适应性免疫系统会受到严重影响,导致血清免疫球蛋白水平下降。这项试验的目的是研究静脉注射免疫球蛋白(IVIG)是否能预防小儿急性淋巴细胞白血病患者因发热入院。这项随机对照试验是荷兰全国多中心 ALL 研究的一项子试验。1-19岁的中危(MR)ALL患者被随机分为两组,一组接受IVIG预防治疗(从确诊后第22天开始,每三周注射一次0.7克/千克IVIG),另一组接受定义明确的标准治疗(对照组)。从2012年10月到2019年3月,91名(51%)患者被随机分配到IVIG预防组,86名(49%)患者被分配到对照组。在IVIG预防组中,有206人因发烧入院,而对照组有271人(P=0.011)。IVIG 预防与菌血症无关。不过,与对照组相比,IVIG 预防治疗组因发热且血培养阴性而入院的人数明显减少(113 人对 200 人,P=0.011)。
{"title":"Immunoglobulin prophylaxis prevents hospital admissions for fever in pediatric acute lymphoblastic leukemia: results of a multicenter randomized trial.","authors":"Kirsten A Thus, Hester A De Groot-Kruseman, Pauline Winkler-Seinstra, Marta Fiocco, Heidi Segers, Cor Van den Bos, Inge M Van der Sluis, Wim J E Tissing, Margreet A Veening, Christian Michel Zwaan, Cornelis M Van Tilburg, Rob Pieters, Marc Bierings","doi":"10.3324/haematol.2024.285428","DOIUrl":"https://doi.org/10.3324/haematol.2024.285428","url":null,"abstract":"<p><p>Infections lead to substantial morbidity during treatment of acute lymphoblastic leukemia (ALL) in which the adaptive immune system gets severely affected, leading to declining serum immunoglobulin levels. The aim of this trial was to investigate whether intravenous immunoglobulin (IVIG) prophylaxis in pediatric patients with ALL prevents admissions for fever. This randomized controlled trial was a subtrial of the national Dutch multicenter ALL study. Patients aged 1-19 years with medium risk (MR) ALL were randomized into two groups receiving either IVIG prophylaxis (0.7 g/kg IVIG given every three weeks, starting day 22 after diagnosis) or well defined standard of care (control group). Between October 2012 until March 2019, 91 (51%) patients were randomly assigned to IVIG prophylaxis and 86 (49%) to the control arm. In the IVIG prophylaxis group there were 206 admissions for fever versus 271 in the control group (p=0.011). IVIG prophylaxis was not associated with bacteremia. However, IVIG prophylaxis was associated with significantly less admissions for fever with negative blood cultures compared to the control group (N=113 versus 200, p.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901566","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 : 2024-08-08DOI: 10.3324/haematol.2023.284353
Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, KerryA Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath
Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the Bcell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis in both venetoclax naïve and resistant CLL cells. Significantly, LP-118 is effective in cell lines expressing the BCL2 G101V mutation and in cells expressing BCLXL but lacking BCL2 dependence. Using an immunocompetent mouse model, Eμ-TCL1, LP-118 demonstrates low platelet toxicity, which hampered earlier BCLXL inhibitors. Finally, LP-118 in the RS4;11 and OSU-CLL xenograft models results in decreases in tumor burden and survival advantage, respectively. These results provide a mechanistic rationale for the evaluation of LP-118 for the treatment of venetoclax responsive and relapsed CLL.
{"title":"LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclax-resistant chronic lymphocytic leukemia.","authors":"Janani Ravikrishnan, Daisy Y Diaz-Rohena, Elizabeth Muhowski, Xiaokui Mo, Tzung-Huei Lai, Shrilekha Misra, Charmelle D Williams, John Sanchez, Andrew Mitchell, Suresh Satpati, Elizabeth Perry, Tierney Kaufman, Chaomei Liu, Arletta Lozanski, Gerard Lozanski, KerryA Rogers, Adam S Kittai, Seema A Bhat, Mary C Collins, Matthew S Davids, Nitin Jain, William G Wierda, Rosa Lapalombella, John C Byrd, Fenlai Tan, Yi Chen, Yu Chen, Yue Shen, Stephen P Anthony, Jennifer A Woyach, Deepa Sampath","doi":"10.3324/haematol.2023.284353","DOIUrl":"https://doi.org/10.3324/haematol.2023.284353","url":null,"abstract":"<p><p>Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the Bcell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis in both venetoclax naïve and resistant CLL cells. Significantly, LP-118 is effective in cell lines expressing the BCL2 G101V mutation and in cells expressing BCLXL but lacking BCL2 dependence. Using an immunocompetent mouse model, Eμ-TCL1, LP-118 demonstrates low platelet toxicity, which hampered earlier BCLXL inhibitors. Finally, LP-118 in the RS4;11 and OSU-CLL xenograft models results in decreases in tumor burden and survival advantage, respectively. These results provide a mechanistic rationale for the evaluation of LP-118 for the treatment of venetoclax responsive and relapsed CLL.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901567","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 : 2024-08-08DOI: 10.3324/haematol.2024.285416
Celia Gonzalez-Gil, Mireia Morgades, Thaysa Lopes, Francisco Fuster-Tormo, Pau Montesinos, Pere Barba, Marina Diaz-Beya, Lourdes Hermosin, Clara Maluquer, Jose Gonzalez-Campos, Teresa Bernal, Marta Sitges Arriaga, Lurdes Zamora, Marta Pratcorona, Rodrigo Martino, Maria Jose Larrayoz, Teresa Artola, Anna Torrent, Ferran Vall-Llovera, Mar Tormo, Cristina Gil, Andres Novo, Pilar Martinez-Sanchez, Jordi Ribera, Maria-Paz Queipo, Teresa Gonzalez-Martinez, Monica Cabrero, Antonia Cladera, Jose Cervera, Alberto Orfao, Josep Maria Ribera, Eulalia Genesca
Not available.
不详。
{"title":"Contribution of copy number to improve risk stratification of adult T-cell acute lymphoblastic leukemia patients enrolled in measurable residual disease-oriented trials.","authors":"Celia Gonzalez-Gil, Mireia Morgades, Thaysa Lopes, Francisco Fuster-Tormo, Pau Montesinos, Pere Barba, Marina Diaz-Beya, Lourdes Hermosin, Clara Maluquer, Jose Gonzalez-Campos, Teresa Bernal, Marta Sitges Arriaga, Lurdes Zamora, Marta Pratcorona, Rodrigo Martino, Maria Jose Larrayoz, Teresa Artola, Anna Torrent, Ferran Vall-Llovera, Mar Tormo, Cristina Gil, Andres Novo, Pilar Martinez-Sanchez, Jordi Ribera, Maria-Paz Queipo, Teresa Gonzalez-Martinez, Monica Cabrero, Antonia Cladera, Jose Cervera, Alberto Orfao, Josep Maria Ribera, Eulalia Genesca","doi":"10.3324/haematol.2024.285416","DOIUrl":"https://doi.org/10.3324/haematol.2024.285416","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901563","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 : 2024-08-08DOI: 10.3324/haematol.2023.284721
Yufeng Li, Virág Sági-Kiss, Emma L N James, Inderjeet Dokal, Kenneth E Parkinson, Jacob G Bundy
Not available.
不详。
{"title":"Nucleotide sugars correlate with leukocyte telomere length as part of a dyskeratosis congenita metabolomic plasma signature.","authors":"Yufeng Li, Virág Sági-Kiss, Emma L N James, Inderjeet Dokal, Kenneth E Parkinson, Jacob G Bundy","doi":"10.3324/haematol.2023.284721","DOIUrl":"https://doi.org/10.3324/haematol.2023.284721","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901568","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 : 2024-08-08DOI: 10.3324/haematol.2024.285707
Farnaz Barneh, Joost B Koedijk, Noa E Wijnen, Tom Meulendijks, Minoo Ashtiani, Ester Dunnebach, Noël Dautzenberg, Annelisa M Cornel, Anja Krippner-Heidenreich, Kim Klein, Michel C Zwaan, Jürgen Kuball, Stefan Nierkens, Jacqueline Cloos, Gertjan J L Kaspers, Olaf Heidenreich
Not available.
不详。
{"title":"Repurposing CD19-directed immunotherapies for pediatric t(8;21) acute myeloid leukemia.","authors":"Farnaz Barneh, Joost B Koedijk, Noa E Wijnen, Tom Meulendijks, Minoo Ashtiani, Ester Dunnebach, Noël Dautzenberg, Annelisa M Cornel, Anja Krippner-Heidenreich, Kim Klein, Michel C Zwaan, Jürgen Kuball, Stefan Nierkens, Jacqueline Cloos, Gertjan J L Kaspers, Olaf Heidenreich","doi":"10.3324/haematol.2024.285707","DOIUrl":"https://doi.org/10.3324/haematol.2024.285707","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901569","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 : 2024-08-08DOI: 10.3324/haematol.2024.285724
Paulo Siqueira Do Amaral, Sanjay R Mohan, Kathryn E Beckermann
Not available.
不详。
{"title":"von Hippel- Lindau syndrome-related congenital polycythemia and response to belzutifan.","authors":"Paulo Siqueira Do Amaral, Sanjay R Mohan, Kathryn E Beckermann","doi":"10.3324/haematol.2024.285724","DOIUrl":"https://doi.org/10.3324/haematol.2024.285724","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901570","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 : 2024-08-08DOI: 10.3324/haematol.2024.285879
Dietger Niederwieser, Dirk Hasenclever, Wolfgang E. Berdel, Bart J Biemond, Haifa Al-Ali, Yves Chalandon, Michel Van Gelder, Christian Junghanß, Gösta Gahrton, Mathias Hänel, Rüdiger Hehlmann, Thomas Heinicke, Andreas Hochhaus, Simona Iacobelli, Rien van Marwijk Kooy, Nicolaus Kröger, Jeroen Janssen, Madlen Jentzsch, Frank Breywisch, Mohamad Mohty, Stavroula Masouridi-Levrat, Gert Ossenkoppele, Jacob Passweg, Wolfram Pönisch, Johannes Schetelig, Christoph Schliemann, Sebastian Schwind, Matthias Stelljes, Leo F Verdonck, Vladan Vucinic, Bob Löwenberg, Jan Cornelissen
Given the selection of elderly patients with AML in first complete remission (CR1) the advantage of consolidation with allogeneic hematopoietic cell transplantation (HCT) over chemotherapy is still unclear. Newly diagnosed AML patients in CR1 aged 60-75 years were registered and a donor search initiated. After one consolidation cycle, patients with a matched donor were randomized to HCT with fludarabine/lowdose total body irradiation and cyclosporine/mycophenolate mofetil immunosuppression or conventional non-HCT. Primary outcome was restricted mean leukemia-free survival (RM-LFS) up to five years. Between 2010 and 2017, 245 patients (median age 67 years) were registered at CR1. After one consolidation, 26.9% of patients failed inclusion criteria. Of the 179 (73%) patients still on study, 75.4% had an HLA identical donor. Ten ineligible patients were excluded, and 125 randomized to HCT (n=83) or non-HCT (n=42). The primary outcome RM-LFS up to 5 years was 24.5 months (95%CI:18.9-30.1) in the HCT and 15.6 months (95%CI:10.4-20.8) in the non-HCT arm (p=0.022) due to a decrease in cumulative relapse incidence from 91.1 (95%CI:80.7-100.0) after non-HCT to 37.8 (95%CI:27.2-48.4)% after HCT (p.
{"title":"Hematopoietic cell transplantation for older acute myeloid leukemia patients in first complete remission: results of a randomized phase III study.","authors":"Dietger Niederwieser, Dirk Hasenclever, Wolfgang E. Berdel, Bart J Biemond, Haifa Al-Ali, Yves Chalandon, Michel Van Gelder, Christian Junghanß, Gösta Gahrton, Mathias Hänel, Rüdiger Hehlmann, Thomas Heinicke, Andreas Hochhaus, Simona Iacobelli, Rien van Marwijk Kooy, Nicolaus Kröger, Jeroen Janssen, Madlen Jentzsch, Frank Breywisch, Mohamad Mohty, Stavroula Masouridi-Levrat, Gert Ossenkoppele, Jacob Passweg, Wolfram Pönisch, Johannes Schetelig, Christoph Schliemann, Sebastian Schwind, Matthias Stelljes, Leo F Verdonck, Vladan Vucinic, Bob Löwenberg, Jan Cornelissen","doi":"10.3324/haematol.2024.285879","DOIUrl":"10.3324/haematol.2024.285879","url":null,"abstract":"<p><p>Given the selection of elderly patients with AML in first complete remission (CR1) the advantage of consolidation with allogeneic hematopoietic cell transplantation (HCT) over chemotherapy is still unclear. Newly diagnosed AML patients in CR1 aged 60-75 years were registered and a donor search initiated. After one consolidation cycle, patients with a matched donor were randomized to HCT with fludarabine/lowdose total body irradiation and cyclosporine/mycophenolate mofetil immunosuppression or conventional non-HCT. Primary outcome was restricted mean leukemia-free survival (RM-LFS) up to five years. Between 2010 and 2017, 245 patients (median age 67 years) were registered at CR1. After one consolidation, 26.9% of patients failed inclusion criteria. Of the 179 (73%) patients still on study, 75.4% had an HLA identical donor. Ten ineligible patients were excluded, and 125 randomized to HCT (n=83) or non-HCT (n=42). The primary outcome RM-LFS up to 5 years was 24.5 months (95%CI:18.9-30.1) in the HCT and 15.6 months (95%CI:10.4-20.8) in the non-HCT arm (p=0.022) due to a decrease in cumulative relapse incidence from 91.1 (95%CI:80.7-100.0) after non-HCT to 37.8 (95%CI:27.2-48.4)% after HCT (p.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901565","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}