Pub Date : 2026-01-29DOI: 10.3324/haematol.2025.300002
Emma S Pool,Cilia R Pothast,Shannah M Gennesse,Esther H M Van Egmond,Julia M Giezen,Sabrina A J Veld,René E M Toes,Frits Koning,Constantijn J M Halkes,Mirjam H M Heemskerk,Dirk Jan A R Moes,Jennifer M-L Tjon
Horse-derived anti-thymocyte globulin (ATGAM) in combination with long-term ciclosporin is the first-line treatment for most immune-mediated aplastic anemia (AA) patients. The exact impact of this immunosuppressive therapy (IST) on hematological recovery and the immune landscape, however, remains poorly understood. We report a longitudinal analysis of the pharmacodynamic effects of ATGAM-based IST in a cohort of 44 AA patients. With flow cytometry we quantified plasma levels of lymphocyte-binding ATGAM, which is believed to mediate the therapeutic effect. Population pharmacokinetic modeling revealed substantial between-patient variability in ATGAM exposure, with higher exposure levels associating to earlier hematologic recovery. ATGAM bound all lymphoid lineages and profoundly depleted Tand NK-cells at high plasma concentrations. Strikingly, ATGAM did not deplete B-cells but instead induced an increase of CD27+ B-cells. Deep immunophenotyping on series of peripheral blood samples collected up to three years after start of IST demonstrated that ATGAM induced rapid depletion of T-cells, including KLRG1+ terminally differentiated CD8+ Tcells and Th17-like CCR6+CD4+ T-cells. Although naïve and pathogen-specific T-cells were also depleted, they recovered quickly, indicating preservation of protective immunity. Notably, CCR6++ B-cells, implicated in AA pathogenesis, escaped ATGAM depletion but reduced gradually over time along with residual potentially pathogenic T-cells, including the CCR6+CD4+ T-cells. This could explain the crucial contribution of long-term ciclosporin to successful IST. Collectively, our results identify ATGAM exposure as a factor influencing hematologic recovery, and indicate that the therapeutic effect of IST goes beyond total lymphodepletion but is rather the result of selective depletion and suppression of key lymphocyte subpopulations.
{"title":"Selective lymphodepletion underlies the efficacy of horse anti-thymocyte globulin-based immunosuppressive therapy in aplastic anemia.","authors":"Emma S Pool,Cilia R Pothast,Shannah M Gennesse,Esther H M Van Egmond,Julia M Giezen,Sabrina A J Veld,René E M Toes,Frits Koning,Constantijn J M Halkes,Mirjam H M Heemskerk,Dirk Jan A R Moes,Jennifer M-L Tjon","doi":"10.3324/haematol.2025.300002","DOIUrl":"https://doi.org/10.3324/haematol.2025.300002","url":null,"abstract":"Horse-derived anti-thymocyte globulin (ATGAM) in combination with long-term ciclosporin is the first-line treatment for most immune-mediated aplastic anemia (AA) patients. The exact impact of this immunosuppressive therapy (IST) on hematological recovery and the immune landscape, however, remains poorly understood. We report a longitudinal analysis of the pharmacodynamic effects of ATGAM-based IST in a cohort of 44 AA patients. With flow cytometry we quantified plasma levels of lymphocyte-binding ATGAM, which is believed to mediate the therapeutic effect. Population pharmacokinetic modeling revealed substantial between-patient variability in ATGAM exposure, with higher exposure levels associating to earlier hematologic recovery. ATGAM bound all lymphoid lineages and profoundly depleted Tand NK-cells at high plasma concentrations. Strikingly, ATGAM did not deplete B-cells but instead induced an increase of CD27+ B-cells. Deep immunophenotyping on series of peripheral blood samples collected up to three years after start of IST demonstrated that ATGAM induced rapid depletion of T-cells, including KLRG1+ terminally differentiated CD8+ Tcells and Th17-like CCR6+CD4+ T-cells. Although naïve and pathogen-specific T-cells were also depleted, they recovered quickly, indicating preservation of protective immunity. Notably, CCR6++ B-cells, implicated in AA pathogenesis, escaped ATGAM depletion but reduced gradually over time along with residual potentially pathogenic T-cells, including the CCR6+CD4+ T-cells. This could explain the crucial contribution of long-term ciclosporin to successful IST. Collectively, our results identify ATGAM exposure as a factor influencing hematologic recovery, and indicate that the therapeutic effect of IST goes beyond total lymphodepletion but is rather the result of selective depletion and suppression of key lymphocyte subpopulations.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"74 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073204","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 : 2026-01-29DOI: 10.3324/haematol.2025.300043
Ji Yun Lee,Eun-Jung Jung,Soyean Kwon,Sang-A Kim,Jeong-Ok Lee,Kyungdo Han,Soo-Mee Bang
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder with a risk of progression to multiple myeloma. Metabolic syndrome (MetS) is implicated in cancer development, yet its association with MGUS remains unclear. We examined MetS as a risk factor for MGUS in a large Korean cohort. In a retrospective cohort study using the National Health Information Database, we analyzed 4,453,504 adults undergoing health checkups in 2012, followed through 2022. MetS was defined by NCEP-ATP III criteria. Over a median 9.3-year follow-up, 1,241 MGUS cases were identified. MetS was associated with a 28% increased MGUS risk (HR: 1.28, 95% CI: 1.14-1.44). Risk escalated with more MetS components, peaking at 76% for five components (HR: 1.76, 95% CI: 1.35-2.30). Low HDL cholesterol, hypertension, and central obesity were key risk factors, with higher risks in males and younger adults (20-39 years). Longitudinal analysis showed MetS onset (HR: 1.25, 95% CI: 1.06-1.47) or persistence (HR: 1.25, 95% CI: 1.06-1.48) increased MGUS risk compared to persistent MetS absence, whereas MetS resolution showed no significant risk increase over persistent MetS absence. MetS increases MGUS risk, particularly in males and younger individuals. Resolving MetS may mitigate MGUS risk, supporting targeted metabolic interventions.
{"title":"Metabolic syndrome and risk of monoclonal gammopathy of undetermined significance: a large Korean cohort study.","authors":"Ji Yun Lee,Eun-Jung Jung,Soyean Kwon,Sang-A Kim,Jeong-Ok Lee,Kyungdo Han,Soo-Mee Bang","doi":"10.3324/haematol.2025.300043","DOIUrl":"https://doi.org/10.3324/haematol.2025.300043","url":null,"abstract":"Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder with a risk of progression to multiple myeloma. Metabolic syndrome (MetS) is implicated in cancer development, yet its association with MGUS remains unclear. We examined MetS as a risk factor for MGUS in a large Korean cohort. In a retrospective cohort study using the National Health Information Database, we analyzed 4,453,504 adults undergoing health checkups in 2012, followed through 2022. MetS was defined by NCEP-ATP III criteria. Over a median 9.3-year follow-up, 1,241 MGUS cases were identified. MetS was associated with a 28% increased MGUS risk (HR: 1.28, 95% CI: 1.14-1.44). Risk escalated with more MetS components, peaking at 76% for five components (HR: 1.76, 95% CI: 1.35-2.30). Low HDL cholesterol, hypertension, and central obesity were key risk factors, with higher risks in males and younger adults (20-39 years). Longitudinal analysis showed MetS onset (HR: 1.25, 95% CI: 1.06-1.47) or persistence (HR: 1.25, 95% CI: 1.06-1.48) increased MGUS risk compared to persistent MetS absence, whereas MetS resolution showed no significant risk increase over persistent MetS absence. MetS increases MGUS risk, particularly in males and younger individuals. Resolving MetS may mitigate MGUS risk, supporting targeted metabolic interventions.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"143 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073137","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 : 2026-01-29DOI: 10.3324/haematol.2025.289200
Eve Roman,Timothy Bagguley,Simon Crouch,Alexandra Smith,Daniel Painter,Debra Howell,Russell Patmore,Reuben Tooze,Catherine Cargo,Ruth De Tute,Andrew Rawstron,Gordon Cook,Christopher Parrish,Frances Seymour
Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell disorder with well described risks of progression to myeloma and lymphoplasmacytic lymphoma. Using data from an established UK population-based cohort of haematological malignancies and premalignancies, we investigated patient and disease characteristics, subsequent haematological malignancy, and survival in 4651 people diagnosed with MGUS 2005-2019. The 5-year net (relative) survival (disease-specific estimate of the probability of survival) of MGUS patients was 87.8% (95% Confidence Interval 85.9-89.7), with males (83.8%; 95% CI 81.0-86.6) more affected than females (92.2%; 95% CI 89.7-94.7). The proportion of subsequent haematological malignancies was also higher in males than females (8.8% versus 5.3%; P.
意义不明的单克隆伽玛病（MGUS）是一种常见的浆细胞疾病，有进展为骨髓瘤和淋巴浆细胞性淋巴瘤的风险。利用英国基于人群的血液恶性肿瘤和恶性前肿瘤队列的数据，研究人员调查了2005-2019年诊断为MGUS的4651人的患者和疾病特征、随后的血液恶性肿瘤和生存率。MGUS患者的5年净（相对）生存率（疾病特异性生存概率估计）为87.8%(95%置信区间85.9-89.7)，男性（83.8%;95% CI 81.0-86.6）比女性（92.2%;95% CI 89.7-94.7）更受影响。男性随后发生血液系统恶性肿瘤的比例也高于女性(8.8%比5.3%；P。
{"title":"Male sex adversely impacts survival and myeloid malignancy risk in MGUS: a real-world population-based study.","authors":"Eve Roman,Timothy Bagguley,Simon Crouch,Alexandra Smith,Daniel Painter,Debra Howell,Russell Patmore,Reuben Tooze,Catherine Cargo,Ruth De Tute,Andrew Rawstron,Gordon Cook,Christopher Parrish,Frances Seymour","doi":"10.3324/haematol.2025.289200","DOIUrl":"https://doi.org/10.3324/haematol.2025.289200","url":null,"abstract":"Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell disorder with well described risks of progression to myeloma and lymphoplasmacytic lymphoma. Using data from an established UK population-based cohort of haematological malignancies and premalignancies, we investigated patient and disease characteristics, subsequent haematological malignancy, and survival in 4651 people diagnosed with MGUS 2005-2019. The 5-year net (relative) survival (disease-specific estimate of the probability of survival) of MGUS patients was 87.8% (95% Confidence Interval 85.9-89.7), with males (83.8%; 95% CI 81.0-86.6) more affected than females (92.2%; 95% CI 89.7-94.7). The proportion of subsequent haematological malignancies was also higher in males than females (8.8% versus 5.3%; P.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"30 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073145","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 : 2026-01-29DOI: 10.3324/haematol.2025.288955
Diguang Wen,Zhenxiang Peng,Jianchuan Deng,National Natural Science Foundation Of China No National-Level Dietary Patterns And Acute Myeloid Leukemia A Global Ecological Analysis
Not available.
不可用。
{"title":"National-level dietary patterns and acute myeloid leukemia: a global ecological analysis.","authors":"Diguang Wen,Zhenxiang Peng,Jianchuan Deng,National Natural Science Foundation Of China No National-Level Dietary Patterns And Acute Myeloid Leukemia A Global Ecological Analysis","doi":"10.3324/haematol.2025.288955","DOIUrl":"https://doi.org/10.3324/haematol.2025.288955","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"8 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073139","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}
{"title":"Diabetes mellitus and diabetes-related complications are common in patients with myelodysplastic syndromes but Hemoglobin A1C is an inadequate marker.","authors":"Ariel Israel,Roi Gat,Howard Oster,Yakir Moshe,Itamar Raz,Moshe Mittelman,Eugene Merzon","doi":"10.3324/haematol.2025.300022","DOIUrl":"https://doi.org/10.3324/haematol.2025.300022","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"281 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073205","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 : 2026-01-29DOI: 10.3324/haematol.2025.300339
Kim G Hankey,Aaron P Rapoport
Not available.
不可用。
{"title":"Would you, could you drive CARs to point-of-care manufacturing? Yes, you should!","authors":"Kim G Hankey,Aaron P Rapoport","doi":"10.3324/haematol.2025.300339","DOIUrl":"https://doi.org/10.3324/haematol.2025.300339","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"43 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073377","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}
Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by dysregulated megakaryopoiesis and expansion of neoplastic hematopoietic stem cells (HSCs). Megakaryocytes (MKs) not only regulate HSC function but also shape immune responses within the marrow niche. Using an aging murine model of MPN with MK-restricted JAK2V617F expression, we investigated the immunomodulatory roles of mutant MKs. Compared to wild-type MKs, aged mutant MKs exhibit enhanced antigen uptake and MHC I presentation, secretion of pro-inflammatory cytokines (PF4, TGFβ, IL-1β), and induction of T cell dysregulation in the marrow niche. In chimeric murine models with co-existing wild-type and JAK2V617F mutant hematopoietic cells, enhanced MK immune activity correlates with mutant cell expansion and MPN development. Single-cell RNA sequencing revealed that aging amplifies JAK2V617F MK-driven immune remodeling. Notably, aged mutant MKs showed marked upregulation of LINE-1 (long-interspersed element-1) retrotransposon transcripts alongside elevated innate immune sensors cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), implicating retrotransposon activity in niche inflammation. In human MPN marrow, immunohistochemistry detected LINE-1-encoded protein ORF1p in MKs from 12 of 13 MPN patients, but not in orthopedic controls (n=5). These findings identify MKs as active immune regulators in MPNs, with JAK2V617F mutation and aging synergizing to reprogram MKs into inflammatory, immunemodulatory niche cells. LINE-1 activation emerges as a potential driver of chronic marrow inflammation and a targetable mechanism in clonal hematopoiesis and MPN progression.
{"title":"Immunomodulatory role of megakaryocytes in the hematopoietic niche of myeloproliferative neoplasms.","authors":"Xiaoxi Yang,Sandy Lee,Kyla Masarik,Tameena Ahmed,Lei Zheng,Huichun Zhan","doi":"10.3324/haematol.2025.288948","DOIUrl":"https://doi.org/10.3324/haematol.2025.288948","url":null,"abstract":"Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by dysregulated megakaryopoiesis and expansion of neoplastic hematopoietic stem cells (HSCs). Megakaryocytes (MKs) not only regulate HSC function but also shape immune responses within the marrow niche. Using an aging murine model of MPN with MK-restricted JAK2V617F expression, we investigated the immunomodulatory roles of mutant MKs. Compared to wild-type MKs, aged mutant MKs exhibit enhanced antigen uptake and MHC I presentation, secretion of pro-inflammatory cytokines (PF4, TGFβ, IL-1β), and induction of T cell dysregulation in the marrow niche. In chimeric murine models with co-existing wild-type and JAK2V617F mutant hematopoietic cells, enhanced MK immune activity correlates with mutant cell expansion and MPN development. Single-cell RNA sequencing revealed that aging amplifies JAK2V617F MK-driven immune remodeling. Notably, aged mutant MKs showed marked upregulation of LINE-1 (long-interspersed element-1) retrotransposon transcripts alongside elevated innate immune sensors cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), implicating retrotransposon activity in niche inflammation. In human MPN marrow, immunohistochemistry detected LINE-1-encoded protein ORF1p in MKs from 12 of 13 MPN patients, but not in orthopedic controls (n=5). These findings identify MKs as active immune regulators in MPNs, with JAK2V617F mutation and aging synergizing to reprogram MKs into inflammatory, immunemodulatory niche cells. LINE-1 activation emerges as a potential driver of chronic marrow inflammation and a targetable mechanism in clonal hematopoiesis and MPN progression.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"222 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015128","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 : 2026-01-22DOI: 10.3324/haematol.2025.300060
Robin Foà,Sabina Chiaretti,Felicetto Ferrara,Giovanni Pizzolo
Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) is today a curable disease. In the real life, too many adult ALL patients are not adequately worked up at diagnosis and treated, and this occurs in particular in elderly/old individuals. We hereby discuss, through representative case descriptions, how Ph+ ALL patients diagnosed in their seventh, eight and nineth decade of life through a timely, accurate and personalized tyrosine kinase inhibitor (TKI) administration, in the absence of systemic chemotherapy, can experience long-lived responses, minimal residual disease negativity, and a good quality of life. To an extent that stopping TKI administration can also be considered. This perspective article represents a proof of concept that nowadays even in elderly/old Ph+ ALL the disease can be cured or kept under prolonged control if adequately managed.
{"title":"Optimal management of elderly/old Ph+ acute lymphoblastic leukemia patients.","authors":"Robin Foà,Sabina Chiaretti,Felicetto Ferrara,Giovanni Pizzolo","doi":"10.3324/haematol.2025.300060","DOIUrl":"https://doi.org/10.3324/haematol.2025.300060","url":null,"abstract":"Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) is today a curable disease. In the real life, too many adult ALL patients are not adequately worked up at diagnosis and treated, and this occurs in particular in elderly/old individuals. We hereby discuss, through representative case descriptions, how Ph+ ALL patients diagnosed in their seventh, eight and nineth decade of life through a timely, accurate and personalized tyrosine kinase inhibitor (TKI) administration, in the absence of systemic chemotherapy, can experience long-lived responses, minimal residual disease negativity, and a good quality of life. To an extent that stopping TKI administration can also be considered. This perspective article represents a proof of concept that nowadays even in elderly/old Ph+ ALL the disease can be cured or kept under prolonged control if adequately managed.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"101 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015155","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 : 2026-01-22DOI: 10.3324/haematol.2025.289179
Michael J R Desborough,Joanne L Mitchell,Polly Whitworth,Ashifa Al Juwaiser,Tanya Sage,Neline Kriek,Gemma Little,Sakthivel Vaiyapuri,Jonathan M Gibbins,Alexander P Bye
Not available.
不可用。
{"title":"Recombinant von Willebrand Factor (vonicog alfa) reduces platelet inhibition caused by antiplatelet drugs and has potential as an acute haemostatic agent.","authors":"Michael J R Desborough,Joanne L Mitchell,Polly Whitworth,Ashifa Al Juwaiser,Tanya Sage,Neline Kriek,Gemma Little,Sakthivel Vaiyapuri,Jonathan M Gibbins,Alexander P Bye","doi":"10.3324/haematol.2025.289179","DOIUrl":"https://doi.org/10.3324/haematol.2025.289179","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"30 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015409","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}
Patients ≥ 70 years with relapsed/refractory acute myeloid leukemia (AML) have an extremely poor prognosis. we adopted a sequential therapy approach, aiming to proceed directly to allogeneic hematopoietic cell transplantation (HCT) despite active disease. We analyzed results of all consecutive patients aged over 70 years and diagnosed with primary refractory/relapsed AML who underwent HCT with sequential therapy approach (FITCy regimen) in the Aviv Sourasky Medical Center. 51 patients (median age 72 years, primary refractory, n=42/relapse, n=9). Median follow-up was 35 (range, 12-91) months. Incidences of overall and grade 3-4 acute GVHD were 39.2% (95% CI, 25.6-52.8%), and 5.9% (95% CI, 0.0-12.5%), respectively. Incidences of overall and moderate-severe chronic GVHD were 40.0% (95% CI, 25.7%-57.1%) and 29.4% (95% CI, 13.2%-46.9%), respectively. Non-relapse mortality at 3 years was 36% (95%CI 22%-49%).42/51 patients (82.4%) had CR on d+30 post HCT. Relapse incidence at 3 years was 27.8% (95% CI 14.3%-41.2%). GVHD-free relapse-free and overall survival (OS) at 3-years were 30% (95%CI 19%-47%) and 31% (95% CI 17%-55%), respectively. Multivariable analysis showed that worse ELN-2022 score, relapsed AML (vs. primary-refractory), not receiving ATG, and lower albumin prior to conditioning, were associated with higher mortality. We developed a model to predict OS that showed median OS in the low-, intermediate-, and high-risk group, not reached, 32.9 months, and 2.1 months, respectively, p.
{"title":"Sequential therapy with allogeneic HCT in patients aged ≥70 years with active AML: a singlecenter retrospective analysis.","authors":"Odelia Amit,Gil Fridberg,Yakir Moshe,Inna Ospovat,Yehonatan Sherf,Dina Tshernichovsky,Chen Karni,Irit Avivi,Ron Ram","doi":"10.3324/haematol.2025.300184","DOIUrl":"https://doi.org/10.3324/haematol.2025.300184","url":null,"abstract":"Patients ≥ 70 years with relapsed/refractory acute myeloid leukemia (AML) have an extremely poor prognosis. we adopted a sequential therapy approach, aiming to proceed directly to allogeneic hematopoietic cell transplantation (HCT) despite active disease. We analyzed results of all consecutive patients aged over 70 years and diagnosed with primary refractory/relapsed AML who underwent HCT with sequential therapy approach (FITCy regimen) in the Aviv Sourasky Medical Center. 51 patients (median age 72 years, primary refractory, n=42/relapse, n=9). Median follow-up was 35 (range, 12-91) months. Incidences of overall and grade 3-4 acute GVHD were 39.2% (95% CI, 25.6-52.8%), and 5.9% (95% CI, 0.0-12.5%), respectively. Incidences of overall and moderate-severe chronic GVHD were 40.0% (95% CI, 25.7%-57.1%) and 29.4% (95% CI, 13.2%-46.9%), respectively. Non-relapse mortality at 3 years was 36% (95%CI 22%-49%).42/51 patients (82.4%) had CR on d+30 post HCT. Relapse incidence at 3 years was 27.8% (95% CI 14.3%-41.2%). GVHD-free relapse-free and overall survival (OS) at 3-years were 30% (95%CI 19%-47%) and 31% (95% CI 17%-55%), respectively. Multivariable analysis showed that worse ELN-2022 score, relapsed AML (vs. primary-refractory), not receiving ATG, and lower albumin prior to conditioning, were associated with higher mortality. We developed a model to predict OS that showed median OS in the low-, intermediate-, and high-risk group, not reached, 32.9 months, and 2.1 months, respectively, p.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"64 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015411","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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