Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.091
Samaher Sukkar MD , Katie Liu MS , Scott Gillespie MS , Tami D. John MD , Allistair Abraham MD , Rikin K Shah MD , Deepak Chellapandian MD MBBS , Monica Bhatia MD , Christine Camacho-Bydume MD , Sonali Chaudhury MD, MBBS , Michael J Eckrich MD MPH , Gregory MT Guilcher MD , Dr. Jennifer J. Jaroscak MD , Kimberly A. Kasow DO , Alexander Ngwube MD , Hemalatha G Rangarajan MD , John Horan MD, MPH , Lakshmanan Krishnamurti MD , Shalini Shenoy MD , Niti Dham MD , Elizabeth O. Stenger MD MSc
Cardiac dysfunction causes morbidity and mortality in sickle cell disease (SCD). Allogeneic hematopoietic cell transplantation (HCT) is the most common curative option, yet its impact on long-term cardiac function is not well defined in multicenter cohorts. After our Sickle cell Transplant Advocacy and Research (STAR) retrospective registry analysis on long-term organ function, we sought to complete more detailed cardiac function analysis and determine predictors of dysfunction.
This retrospective cohort study of pediatric patients (pts) with SCD post-HCT with pre- and post-HCT echocardiograms (echo) in the STAR registry (Figure 1). Additional echo data was extracted from source documents and linked to existing data. Cardiac dysfunction was defined as ejection fraction (EF) <55% or shortening fraction (SF) <28%. Data were summarized as median (IQR) or N (%). Linear mixed effect models were used to compare pre- to post-HCT data, accounting for within-pt clustering. Associations between risk factors and cardiac dysfunction were assessed using Firth logistic regression.
Within 228 pts (Table), age at HCT was 8.8 years (yrs), and most pts received matched related donor (MRD; 75%) bone marrow (76%) after myeloablative conditioning (MAC; 76%). Engraftment was prompt, with most pts remaining alive and free from severe graft-versus-host disease (GVHD) or rejection. At 3.4 yrs (2.2, 6.3) post-HCT, while EF significantly decreased, SF was stable (Figure 2A). Left ventricular (LV) size and function significantly decreased (Figures 2B-C). Mitral and tricuspid valve (MV, TV) flow significantly decreased (Figure 2D), as did tricuspid regurgitant jet velocity (TRJV; Figure 2A). While most (93%) remained free of cardiac dysfunction, significantly more pts had low EF (1.6%→6.7%, p=0.008) or SF (0.9%→4.1%, p=0.022) post-HCT. Controlling for MAC and cytoxan (Cy) dose, male sex was significantly associated with post-HCT cardiac dysfunction and age <6 yrs was protective.
In pediatric SCD, HCT is associated with favorable reverse remodeling and reduced pulmonary pressures, but with a modest EF decrease. Early HCT appears protective and male sex increases risk. Longer follow-up is needed to clarify durability and clinical significance of these findings. Additional analyses of predictors for diastolic dysfunction are planned.
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Pub Date : 2026-02-01DOI: 10.1016/S2666-6367(25)02660-0
{"title":"Officers and Directors of ASTCT","authors":"","doi":"10.1016/S2666-6367(25)02660-0","DOIUrl":"10.1016/S2666-6367(25)02660-0","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page A4"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.105
Fnu Amisha MD , Corbin Wright MD , Sean Haney MD , Pujan Patel MD , Biwei Cao PhD , Jongphil Kim PhD , Onyee Chan MD , Andrew T Kuykendall MD , Nancy Torres MD , Reshma Ramlal MD , Rawan Faramand MD , Abu-Sayeef Mirza MD, MPH , Fabiana Perna MD, PhD , Allison Walker MD , Asmita Mishra MD , Lia Elena Perez MD , Eric Padron MD , Aleksandr Lazaryan MD, MPH, PhD , Farhad Khimani MD , David A. Sallman MD , Nelli Bejanyan MD
<div><h3>Background</h3><div>Older age is a known risk factor for non-relapse mortality (NRM) after allogenic stem cell transplantation (HCT). Reduced-intensity conditioning (RIC) has made HCT- the only curative option- more accessible to elderly AML and MDS patients (pts). Age adjusted HCT comorbidity index (HCT-CI), though widely use, was developed from a heterogeneous cohort and its predictive accuracy may be limited by changes in clinical practice and patient characteristics over time. We present additional predictors of NRM and overall survival (OS) to introduce RECI for patients ≥60 years (yrs) receiving HCT for AML/MDS.</div></div><div><h3>Methods</h3><div>In this single-center retrospective study, we evaluated predictive markers and survival outcomes in 941 pts aged ≥60 yrs who underwent HCT (2005-2023) for AML or MDS (Fig 1). The primary endpoints were 2-year NRM and OS. Adjusted hazard ratios (HR) of significant variables from multivariate Cox model of NRM were converted to an integer score to develop the RECI. HR of 1.3-2, 2.1-3, and 3-4, were assigned weights of 1, 2, and 3, respectively. RECI, the sum of integer weights, was used to stratify patients according to 2-year NRM and OS.</div></div><div><h3>Results</h3><div>Baseline characteristics are summarized (Fig 1, 2). At 2-year post-HCT, NRM was 22% (95% CI: 20-25) and OS was 59% (95% CI: 56-62) for the entire cohort. In multivariate analysis, NRM and OS were similar in patients aged 60-69 and ≥70 years. NRM was higher with HCT-CI ≥3 (HR 1.61, 95% CI 1.19- 2.18, p=0.002), eGFR <60 (HR 1.83, 95% CI 1.26- 2.67, p=0.002), albumin <3.5 (HR 1.83, 95% CI 1.25- 2.65, p=0.002), and CMV R+ (HR 1.36, 95% CI 1.01- 1.83, p=0.04). OS was worse with HCT-CI ≥3 (HR 1.46, 95% CI 1.15- 1.86, p=0.0018), albumin <3.5 (HR 1.54, 95% CI 1.1- 2.16, p=0.01), ferritin ≥700 (HR 1.43, 95% CI 1.10- 1.87, p=0.007), and high risk AML/MDS (HR 1.58, 95% CI 1.25- 1.99, p= <0.0001).</div><div>Components of RECI are summarized (Fig 3). RECI ranged from 0 to 4 and stratified patients into 3 risk groups with score of 0 (33%), 1 (53%), and ≥2 (14%). RECI was strongly prognostic for 2-year NRM ranging from 15% (95% CI: 11-19) in RECI 0, 22% (95% CI: 19-26) in RECI 1 (HR=1.6, 95% CI 1.13-2.25, p=0.009) and 38% (95% CI: 29-46) in RECI ≥2 (HR=3.0, 95% CI 1.99-4.46, p<0.001) (Fig 4). The prognostic significance of RECI was also determined for OS ranging from 66% (95% CI: 61-72) in RICI 0, 58% (95% CI: 54-63) in RECI 1 (HR=1.3, 95% CI 1.04-1.68, p=0.02) and 44% (95% CI: 36-53) in RECI ≥2 (HR=2.2, 95% CI 1.60-2.91, p<0.0001) (Fig 4).</div></div><div><h3>Conclusions</h3><div>RECI applied at time of HCT strongly predicts NRM and OS in patients aged ≥60 with AML/MDS. No difference in survival outcomes was observed in patients aged 60-69 and ≥70 yrs. While elderly patients should be considered candidates for HCT, predictive factors that affect NRM and OS should be carefully assessed prior to HCT. If validated in l
背景：年龄是同种异体干细胞移植（HCT）术后非复发死亡率（NRM）的已知危险因素。低强度调节（RIC）使得HCT（唯一的治疗选择）更容易被老年AML和MDS患者接受。年龄调整的HCT共病指数（HCT- ci）虽然被广泛使用，但它是从异质队列中发展而来的，其预测准确性可能受到临床实践和患者特征随时间变化的限制。我们提出了NRM和总生存期（OS）的其他预测因素，以引入≥60岁（yrs）接受HCT治疗的AML/MDS患者的RECI。在这项单中心回顾性研究中，我们评估了941名年龄≥60岁的AML或MDS患者（2005-2023年）的预测标志物和生存结果（图1）。主要终点为2年NRM和OS。将NRM多变量Cox模型中显著变量的校正风险比（HR）转换为整数分值，形成RECI。HR分别为1.3-2、2.1-3和3-4，权重分别为1、2和3。采用整数权值和RECI，根据2年NRM和OS对患者进行分层。基线特征总结（图1、2）。在hct后2年，整个队列的NRM为22% (95% CI: 20-25)， OS为59% （95% CI: 56-62）。在多变量分析中，60-69岁和≥70岁患者的NRM和OS相似。当HCT-CI≥3 （HR 1.61, 95% CI 1.19- 2.18, p=0.002）、eGFR <60 （HR 1.83, 95% CI 1.26- 2.67, p=0.002）、白蛋白<；3.5 （HR 1.83, 95% CI 1.25- 2.65, p=0.002）和CMV R+ (HR 1.36, 95% CI 1.01- 1.83, p=0.04)时，NRM较高。HCT-CI≥3 （HR 1.46, 95% CI 1.15- 1.86, p=0.0018）、白蛋白3.5 （HR 1.54, 95% CI 1.1- 2.16, p=0.01）、铁蛋白≥700 （HR 1.43, 95% CI 1.10- 1.87, p=0.007）和高风险AML/MDS （HR 1.58, 95% CI 1.25- 1.99, p= <0.0001）的OS较差。总结了RECI的组成部分（图3）。RECI评分范围从0到4，将患者分为3个危险组，分别为0分（33%）、1分（53%）和≥2分（14%）。RECI对2年NRM有很强的预后作用，RECI 0组为15% (95% CI: 11-19)， RECI 1组为22% (95% CI: 19-26) (HR=1.6, 95% CI 1.13-2.25, p=0.009)， RECI≥2组为38% (95% CI: 29-46) (HR=3.0, 95% CI 1.99-4.46, p<0.001)（图4）。RECI对OS的预后意义也被确定，范围从RICI 0的66% (95% CI: 61-72)， RECI 1的58% (95% CI: 54-63) （HR=1.3, 95% CI 1.04-1.68, p=0.02）和RECI≥2的44% (95% CI: 36-53) (HR=2.2, 95% CI 1.60-2.91, p<0.0001)（图4）。结论在HCT时应用reci对≥60岁AML/MDS患者的NRM和OS有很强的预测作用。60-69岁和≥70岁患者的生存结局无差异。虽然老年患者应被视为HCT的候选者，但在HCT之前应仔细评估影响NRM和OS的预测因素。如果在大型独立HCT队列中得到验证，RECI作为一种新的预后工具可以帮助老年患者进行HCT的适当选择。
{"title":"Refined Elderly Comorbidity Index (RECI) Is Highly Predictive of Post-Transplant Survival in Older Adults with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)","authors":"Fnu Amisha MD , Corbin Wright MD , Sean Haney MD , Pujan Patel MD , Biwei Cao PhD , Jongphil Kim PhD , Onyee Chan MD , Andrew T Kuykendall MD , Nancy Torres MD , Reshma Ramlal MD , Rawan Faramand MD , Abu-Sayeef Mirza MD, MPH , Fabiana Perna MD, PhD , Allison Walker MD , Asmita Mishra MD , Lia Elena Perez MD , Eric Padron MD , Aleksandr Lazaryan MD, MPH, PhD , Farhad Khimani MD , David A. Sallman MD , Nelli Bejanyan MD","doi":"10.1016/j.jtct.2025.12.105","DOIUrl":"10.1016/j.jtct.2025.12.105","url":null,"abstract":"<div><h3>Background</h3><div>Older age is a known risk factor for non-relapse mortality (NRM) after allogenic stem cell transplantation (HCT). Reduced-intensity conditioning (RIC) has made HCT- the only curative option- more accessible to elderly AML and MDS patients (pts). Age adjusted HCT comorbidity index (HCT-CI), though widely use, was developed from a heterogeneous cohort and its predictive accuracy may be limited by changes in clinical practice and patient characteristics over time. We present additional predictors of NRM and overall survival (OS) to introduce RECI for patients ≥60 years (yrs) receiving HCT for AML/MDS.</div></div><div><h3>Methods</h3><div>In this single-center retrospective study, we evaluated predictive markers and survival outcomes in 941 pts aged ≥60 yrs who underwent HCT (2005-2023) for AML or MDS (Fig 1). The primary endpoints were 2-year NRM and OS. Adjusted hazard ratios (HR) of significant variables from multivariate Cox model of NRM were converted to an integer score to develop the RECI. HR of 1.3-2, 2.1-3, and 3-4, were assigned weights of 1, 2, and 3, respectively. RECI, the sum of integer weights, was used to stratify patients according to 2-year NRM and OS.</div></div><div><h3>Results</h3><div>Baseline characteristics are summarized (Fig 1, 2). At 2-year post-HCT, NRM was 22% (95% CI: 20-25) and OS was 59% (95% CI: 56-62) for the entire cohort. In multivariate analysis, NRM and OS were similar in patients aged 60-69 and ≥70 years. NRM was higher with HCT-CI ≥3 (HR 1.61, 95% CI 1.19- 2.18, p=0.002), eGFR <60 (HR 1.83, 95% CI 1.26- 2.67, p=0.002), albumin <3.5 (HR 1.83, 95% CI 1.25- 2.65, p=0.002), and CMV R+ (HR 1.36, 95% CI 1.01- 1.83, p=0.04). OS was worse with HCT-CI ≥3 (HR 1.46, 95% CI 1.15- 1.86, p=0.0018), albumin <3.5 (HR 1.54, 95% CI 1.1- 2.16, p=0.01), ferritin ≥700 (HR 1.43, 95% CI 1.10- 1.87, p=0.007), and high risk AML/MDS (HR 1.58, 95% CI 1.25- 1.99, p= <0.0001).</div><div>Components of RECI are summarized (Fig 3). RECI ranged from 0 to 4 and stratified patients into 3 risk groups with score of 0 (33%), 1 (53%), and ≥2 (14%). RECI was strongly prognostic for 2-year NRM ranging from 15% (95% CI: 11-19) in RECI 0, 22% (95% CI: 19-26) in RECI 1 (HR=1.6, 95% CI 1.13-2.25, p=0.009) and 38% (95% CI: 29-46) in RECI ≥2 (HR=3.0, 95% CI 1.99-4.46, p<0.001) (Fig 4). The prognostic significance of RECI was also determined for OS ranging from 66% (95% CI: 61-72) in RICI 0, 58% (95% CI: 54-63) in RECI 1 (HR=1.3, 95% CI 1.04-1.68, p=0.02) and 44% (95% CI: 36-53) in RECI ≥2 (HR=2.2, 95% CI 1.60-2.91, p<0.0001) (Fig 4).</div></div><div><h3>Conclusions</h3><div>RECI applied at time of HCT strongly predicts NRM and OS in patients aged ≥60 with AML/MDS. No difference in survival outcomes was observed in patients aged 60-69 and ≥70 yrs. While elderly patients should be considered candidates for HCT, predictive factors that affect NRM and OS should be carefully assessed prior to HCT. If validated in l","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S70-S71"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.043
Thomas E Klingebiel MD, Prof. , Mohana Reddy MD , Deepa Trivedi MD , Kim Hoa Nguyen Thi MD , Sayitov Begali MD , Hayder Shahad Marzook MD , Priya Marwah MD , Aliya Batool MD , Tejashree Sridhar MD , Rajat Kumar Agarwal MR , Jan Soerensen MD , Ali Suliman MD, MSc , Regina Landwehr Mrs , Lawrence Faulkner MD
Introduction
Sankalp India Foundation, in collaboration with DKMS and Cure2Children, developed a cost-conscious pediatric BMT model for low- and middle-income countries (LMICs). The strategy is supported by the DKMS Access to Treatment and Transplant program (ATT) and hinges on low-risk matched sibling donor (MSD) transplants for severe hemoglobinopathies delivered for an average cost of $12,000 including follow up.
Objectives
Here we summarize the outcomes of 141 MSD BMTs for hemoglobinopathies done directly in LMICs and compare experienced vs. startup centres assisted by the DKMS ATT program.
Methods
On-site and online expert guidance relying on a comprehensive online IT platform including electronical medical records and continuing quality improvement tools was implemented. Major emphasis was given to nurses’ training, and professional development. The protocol consisted of pre-transplant immunosuppression with fludarabine/dexamethasone followed one month later by fludarabine, busulfan and cyclophosphamide. G-CSF-primed bone marrow was used as stem cell source followed by cyclosporine/methotrexate prophylaxis. Moderate to severe Graft vs. Host Disease - and Event-Free Survival (GEFS) composite outcome was compared between established (BMJH-Bangalore, CIMS-Ahmedabad, SEAIT-Jaipur, India and ANTH-Islamabad, Pakistan) and startup centres (NCMC-Tashkent, Uzbekistan, HCH-Hue, Vietnam and Al Mujtaba Hospital-Kerbala, Iraq).
Results
A total of 141 consecutive first bone marrow transplants (BMTs) were included in the analysis, consisting 128 patients (median age: 6.04 years; IQR: 4.1–9.1 years) from established centres and 13 patients (median age: 5.12 years; IQR: 4.1–6.1 years) from startup centres.
Of the 128 patients treated at established centres, 122 were diagnosed with thalassemia major and 6 with sickle cell disease (SCD). All 13 patients at the startup centres had thalassemia major with liver size ≤3 cm below the costal margin at transplantation. GEFS was 94% in the established centres and 100% in the startup centres. Overall survival was 97% in established centres and 100% in startup centres, with a median follow-up of 12.8 months and 9.2 months in established respective start up centers. No statistically significant difference in GEFS was observed between the centres as determined by log-rank analysis.
Conclusions
The DKMS ATT platform focusing on low-risk MSD BMT for severe hemoglobinopathies seems to be a safe and effective BMT start up approach in LMICs maximizing initial success rates while promoting sustainability.
{"title":"A Cost-Conscious, and Highly Successful Start-up Strategy for Hematopoietic Cell Transplantation in Low- and Middle-Income Countries Supported By DKMS","authors":"Thomas E Klingebiel MD, Prof. , Mohana Reddy MD , Deepa Trivedi MD , Kim Hoa Nguyen Thi MD , Sayitov Begali MD , Hayder Shahad Marzook MD , Priya Marwah MD , Aliya Batool MD , Tejashree Sridhar MD , Rajat Kumar Agarwal MR , Jan Soerensen MD , Ali Suliman MD, MSc , Regina Landwehr Mrs , Lawrence Faulkner MD","doi":"10.1016/j.jtct.2025.12.043","DOIUrl":"10.1016/j.jtct.2025.12.043","url":null,"abstract":"<div><h3>Introduction</h3><div>Sankalp India Foundation, in collaboration with DKMS and Cure2Children, developed a cost-conscious pediatric BMT model for low- and middle-income countries (LMICs). The strategy is supported by the DKMS Access to Treatment and Transplant program (ATT) and hinges on low-risk matched sibling donor (MSD) transplants for severe hemoglobinopathies delivered for an average cost of $12,000 including follow up.</div></div><div><h3>Objectives</h3><div>Here we summarize the outcomes of 141 MSD BMTs for hemoglobinopathies done directly in LMICs and compare experienced <em>vs.</em> startup centres assisted by the DKMS ATT program.</div></div><div><h3>Methods</h3><div>On-site and online expert guidance relying on a comprehensive online IT platform including electronical medical records and continuing quality improvement tools was implemented. Major emphasis was given to nurses’ training, and professional development. The protocol consisted of pre-transplant immunosuppression with fludarabine/dexamethasone followed one month later by fludarabine, busulfan and cyclophosphamide. G-CSF-primed bone marrow was used as stem cell source followed by cyclosporine/methotrexate prophylaxis. Moderate to severe Graft vs. Host Disease - and Event-Free Survival (GEFS) composite outcome was compared between established (BMJH-Bangalore, CIMS-Ahmedabad, SEAIT-Jaipur, India and ANTH-Islamabad, Pakistan) and startup centres (NCMC-Tashkent, Uzbekistan, HCH-Hue, Vietnam and Al Mujtaba Hospital-Kerbala, Iraq).</div></div><div><h3>Results</h3><div>A total of 141 consecutive first bone marrow transplants (BMTs) were included in the analysis, consisting 128 patients (median age: 6.04 years; IQR: 4.1–9.1 years) from established centres and 13 patients (median age: 5.12 years; IQR: 4.1–6.1 years) from startup centres.</div><div>Of the 128 patients treated at established centres, 122 were diagnosed with thalassemia major and 6 with sickle cell disease (SCD). All 13 patients at the startup centres had thalassemia major with liver size ≤3 cm below the costal margin at transplantation. GEFS was 94% in the established centres and 100% in the startup centres. Overall survival was 97% in established centres and 100% in startup centres, with a median follow-up of 12.8 months and 9.2 months in established respective start up centers. No statistically significant difference in GEFS was observed between the centres as determined by log-rank analysis.</div></div><div><h3>Conclusions</h3><div>The DKMS ATT platform focusing on low-risk MSD BMT for severe hemoglobinopathies seems to be a safe and effective BMT start up approach in LMICs maximizing initial success rates while promoting sustainability.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S25"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.082
Ran Reshef MD, MSc , Stefan O Ciurea MD , Ronald M. Sobecks MD , Dr. Iskra Pusic MD, MScI , Nelli Bejanyan MD , Sagar S. Patel MD , Arpita P. Gandhi MD , Vamsi Kota MD , M. Nabeel Rajeh MD , Piyanuch Kongtim MD, PhD , Jing Shi PhD , Yi Fu PhD , Natali Gulbahce PhD , Nishant Dwivedi MD, PhD , Monzr M. Al Malki MD , Corey Cutler MD MPH
<div><h3>Introduction</h3><div>Early detection of relapses in patients undergoing allogeneic hematopoietic cell transplantation (HCT) may enable early intervention. The ACROBAT study (NCT04635384) evaluates the use of AlloHeme, a next-generation sequencing (NGS)-based, ultra-sensitive monitoring test for relapse prediction in post-HCT patients.</div></div><div><h3>Methods</h3><div>Post-HCT acute myeloid leukemia (AML) and or myelodysplastic syndrome (MDS) patients enrolled in ACROBAT were included in this analysis. Testing was performed at 14 post-HCT time points over 2 years, as outlined in the study protocol. An increase of ≥0.2% in recipient chimerism between two consecutive time points was defined as increasing mixed chimerism (iMC) and an AlloHeme test positive. Treating physicians determined relapses per the Center for International Blood & Marrow Transplant Research criteria. Here we describe the findings of the 18-month interim analysis with the intent of presenting the final study readout for all subjects at Tandem Meetings 2026.</div></div><div><h3>Results</h3><div>Table 1 presents the demographics and disease characteristics of 227 enrolled AML and MDS patients. Out of the 227 enrolled patients, 32 subjects were excluded from the analysis due to events (non-relapse mortality (NRM), study withdrawal, and relapses) that occurred before the two tests used to determine iMC. Among the remaining 195 subjects with 18+ months of follow-up (median, 23.4 months; range, 1.8-24), 37 subjects (19%) experienced relapse, and 26 (13.3%) subjects had non-relapse mortality (NRM). AlloHeme had an AUC of 86% for relapse prediction based on sensitivity (88%), specificity (85%), PPV (60%), and NPV (97%). In comparison, modeling at the STR-PCR threshold of 1% iMC and site-reported multi-flow cytometry measurable residual disease (MFC-MRD) demonstrated lower sensitivity to predict relapse (Table 2). A time-varying risk model showed that the relapse risk for patients with an iMC is 54.0 times (95% CI = 22.4, 142.8; p < 0.001) higher than that of non-iMC patients. 3- and 6-month landmark analyses demonstrated significantly higher relapse incidence in subjects with iMC compared with non-iMC (p-values < 0.05) (Figure 1). Among subjects who were iMC positive before or at the time of the relapse event, the test provided a median lead time of 36 days to clinical relapse (IQR: 18–72 days), with 47% of relapses identified at least 45 days before the relapse.</div><div>Further optimizing the performance for risk prediction by incorporating additional AlloHeme cell subtype analytes into an algorithm improved specificity to >92% and PPV to >74% without affecting sensitivity and NPV.</div></div><div><h3>Conclusion</h3><div>ACROBAT interim results demonstrate that AlloHeme monitoring for post-HCT AML and MDS patients can identify relapses with a significant lead time compared to traditional methods of relapse detection, which could enable timely interventio
{"title":"Acrobat Interim Results: Peripheral Blood-Based Alloheme Test Enables Robust Relapse Surveillance in Post-HCT AML and MDS Patients","authors":"Ran Reshef MD, MSc , Stefan O Ciurea MD , Ronald M. Sobecks MD , Dr. Iskra Pusic MD, MScI , Nelli Bejanyan MD , Sagar S. Patel MD , Arpita P. Gandhi MD , Vamsi Kota MD , M. Nabeel Rajeh MD , Piyanuch Kongtim MD, PhD , Jing Shi PhD , Yi Fu PhD , Natali Gulbahce PhD , Nishant Dwivedi MD, PhD , Monzr M. Al Malki MD , Corey Cutler MD MPH","doi":"10.1016/j.jtct.2025.12.082","DOIUrl":"10.1016/j.jtct.2025.12.082","url":null,"abstract":"<div><h3>Introduction</h3><div>Early detection of relapses in patients undergoing allogeneic hematopoietic cell transplantation (HCT) may enable early intervention. The ACROBAT study (NCT04635384) evaluates the use of AlloHeme, a next-generation sequencing (NGS)-based, ultra-sensitive monitoring test for relapse prediction in post-HCT patients.</div></div><div><h3>Methods</h3><div>Post-HCT acute myeloid leukemia (AML) and or myelodysplastic syndrome (MDS) patients enrolled in ACROBAT were included in this analysis. Testing was performed at 14 post-HCT time points over 2 years, as outlined in the study protocol. An increase of ≥0.2% in recipient chimerism between two consecutive time points was defined as increasing mixed chimerism (iMC) and an AlloHeme test positive. Treating physicians determined relapses per the Center for International Blood & Marrow Transplant Research criteria. Here we describe the findings of the 18-month interim analysis with the intent of presenting the final study readout for all subjects at Tandem Meetings 2026.</div></div><div><h3>Results</h3><div>Table 1 presents the demographics and disease characteristics of 227 enrolled AML and MDS patients. Out of the 227 enrolled patients, 32 subjects were excluded from the analysis due to events (non-relapse mortality (NRM), study withdrawal, and relapses) that occurred before the two tests used to determine iMC. Among the remaining 195 subjects with 18+ months of follow-up (median, 23.4 months; range, 1.8-24), 37 subjects (19%) experienced relapse, and 26 (13.3%) subjects had non-relapse mortality (NRM). AlloHeme had an AUC of 86% for relapse prediction based on sensitivity (88%), specificity (85%), PPV (60%), and NPV (97%). In comparison, modeling at the STR-PCR threshold of 1% iMC and site-reported multi-flow cytometry measurable residual disease (MFC-MRD) demonstrated lower sensitivity to predict relapse (Table 2). A time-varying risk model showed that the relapse risk for patients with an iMC is 54.0 times (95% CI = 22.4, 142.8; p < 0.001) higher than that of non-iMC patients. 3- and 6-month landmark analyses demonstrated significantly higher relapse incidence in subjects with iMC compared with non-iMC (p-values < 0.05) (Figure 1). Among subjects who were iMC positive before or at the time of the relapse event, the test provided a median lead time of 36 days to clinical relapse (IQR: 18–72 days), with 47% of relapses identified at least 45 days before the relapse.</div><div>Further optimizing the performance for risk prediction by incorporating additional AlloHeme cell subtype analytes into an algorithm improved specificity to >92% and PPV to >74% without affecting sensitivity and NPV.</div></div><div><h3>Conclusion</h3><div>ACROBAT interim results demonstrate that AlloHeme monitoring for post-HCT AML and MDS patients can identify relapses with a significant lead time compared to traditional methods of relapse detection, which could enable timely interventio","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S53"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.047
Alfonso Molina MD, MPH , Parveen Shiraz MD , Alyssa Kanegai MPH , Ayesha Fraser CCRP, CHRC , Diana Kordek RN , Caroline Wagner BS , Lindsay Danley BS , Arvind Ramakrishnan BS , Hossein Daghagh MS , Yingwen Huang MS , Gaurav Dhapola MS , Aman Siddiqui BS, MBA , Sally Arai MD, MS , Sushma Bharadwaj MD , Saurabh Dahiya MD, FACP , Hany Elmariah MD , Matthew Frank MD, PhD , Hitomi Hosoya MD, PhD , Vanessa E Kennedy MD , Laura Johnston MD , Lori S. Muffly MD, MS
<div><h3>Background</h3><div>High-risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) remains difficult to cure in adults despite autologous CAR T cells or allogeneic hematopoietic cell transplant (HCT). Building on preclinical work showing CAR T cell safety post-HCT (Ghosh A, Smith M <em>Nature Medicine</em> 2017), we tested whether allogeneic CAR-T cells combined with myeloablative graft-engineered HCT (Orca-T) could enhance antileukemic activity without increasing GVHD or graft failure. We now report final clinical outcomes from this Phase 1 trial (NCT05507827).</div></div><div><h3>Methods</h3><div>This single-center trial tested allogeneic anti-CD19/CD22 CAR T cells combined with myeloablative conditioning and Orca-T (D0 HSPCs/Tregs; D+2 Tcons, per Meyer <em>Blood</em> 2025) in adults with HR B-ALL. Donor-derived CAR T cells were administered on D+2, tacrolimus began on D+3. The primary endpoint was engraftment without grade 3+ acute GVHD at D+42; secondary endpoints included survival outcomes, CAR persistence, and immune reconstitution.</div></div><div><h3>Results</h3><div>Eighteen patients (pts) enrolled between Sept 2022 and May 2025; 16 received both Orca-T and allogeneic CAR T cells; 1 received only Orca-T due to active infection at time of planned CAR T infusion and 1 did not proceed on trial. Median age was 31 years (range, 21–58); 70% were Hispanic, 76% were MRD+ post-induction. Most (76%) received matched sibling grafts; 24% were from matched unrelated donors. All pts have now reached the primary endpoint: engraftment occurred in 100% and no pts have developed 3+ acute GVHD. Acute GVHD occurred in 1 pt (grade 1) and chronic GVHD in 2 pts (1 mild; 1 moderate). There were no high-grade CAR mediated toxicities.</div><div>With median follow-up of 14 months (range, 3-35), disease-free and overall survival are both 100% (Figure 1A, 1B). Figure 1C depicts pre-and post-treatment MRD. Following allogeneic CAR T plus Orca-T, all pts achieved MRD clearance by flow cytometry (10-4) and remain undetectable to date. Two pts with pre-treatment MRD have ongoing detectable MRD by clonoSEQ (10-6) without evidence of relapse. Median time to peak CAR expansion was 13 days. Median circulating CAR T cells at peak expansion was 1,205 copies/100ng DNA, with a median D0-28 AUC of 13,324 copies/100ng DNA. <strong>Figure 2</strong> shows ongoing CAR detection by qPCR (LOD 10 copies/100ng DNA) averaged across patients; only 4 pts have evidence of functional B cell recovery.</div></div><div><h3>Conclusion</h3><div>Here, we report final safety and anti-tumor activity of the combination of allogeneic anti-CD19/CD22 CAR T cells with a myeloablative graft-engineered HCT in pts with HR B-ALL. This paradigm-shifting combination of CAR T and HCT resulted in 100% DFS without graft failure, significant GVHD, or severe CAR-mediated toxicity. We hypothesize this is due to tolerance for CAR molecules, resulting in persistent CAR expression and improved antitumor activity.
成人高危（HR） b细胞急性淋巴细胞白血病（B-ALL）仍然难以治愈，尽管采用自体CAR - T细胞或同种异体造血细胞移植（HCT）。在临床前研究显示HCT后CAR-T细胞安全性的基础上（Ghosh A, Smith M Nature Medicine 2017），我们测试了异体CAR-T细胞联合骨髓清除移植工程HCT （Orca-T）是否可以增强抗白血病活性，而不会增加GVHD或移植物失败。我们现在报告该1期试验（NCT05507827）的最终临床结果。方法：这项单中心试验检测了同种异体抗cd19 /CD22 CAR -T细胞联合清髓调节和Orca-T （D0 HSPCs/Tregs; D+2 Tcons, per Meyer Blood 2025）在成人HR B-ALL患者中的应用。供体来源的CAR - T细胞在D+2给予，他克莫司在D+3开始。主要终点是在D+42时无3级急性GVHD的移植；次要终点包括生存结局、CAR持续性和免疫重建。结果2022年9月至2025年5月入组患者18例；16例同时接受Orca-T和同种异体CAR -T细胞；1例患者在计划CAR -T输注时因活动性感染仅接受了Orca-T， 1例患者未进行试验。中位年龄31岁（范围21-58岁）；70%为西班牙裔，76%为入职后MRD+。大多数（76%）接受了匹配的同胞移植物；24%来自匹配的非亲属捐赠者。所有患者现在都达到了主要终点：移植的发生率为100%，没有患者发展为3+急性GVHD。1例患者发生急性GVHD（1级），2例患者发生慢性GVHD（1例轻度，1例中度）。没有CAR介导的高级别毒性。中位随访14个月（范围3-35），无病生存率和总生存率均为100%（图1A， 1B）。图1C描述了处理前和处理后的MRD。同种异体CAR -T + Orca-T治疗后，所有患者通过流式细胞术（10-4）达到MRD清除，并且迄今为止仍无法检测到。两名治疗前MRD患者通过克隆seq检测到MRD(10-6)，但没有复发的证据。中非共和国扩张达到峰值的中位时间为13天。扩增峰值时循环CAR - T细胞的中位数为1205拷贝/100ng DNA，中位数D0-28 AUC为13324拷贝/100ng DNA。图2显示了正在进行的CAR检测的qPCR （LOD 10拷贝/100ng DNA）在患者中的平均水平；只有4例患者有B细胞功能恢复的证据。结论：我们报告了同种异体抗cd19 /CD22 CAR - T细胞与清骨髓移植工程HCT联合治疗HR B-ALL患者的最终安全性和抗肿瘤活性。这种范式转换的CAR- T和HCT的结合导致了100%的DFS，没有移植物衰竭、明显的GVHD或严重的CAR介导的毒性。我们假设这是由于对CAR分子的耐受性，导致CAR的持续表达和抗肿瘤活性的提高。我们的all-in- all- car - hct代表了一种合理的方法，值得进一步的研究。
{"title":"Mature Outcomes from the Phase I Trial of Orca-T and Allogeneic CD19/CD22 CAR-T cells for Adults with High-Risk B-ALL","authors":"Alfonso Molina MD, MPH , Parveen Shiraz MD , Alyssa Kanegai MPH , Ayesha Fraser CCRP, CHRC , Diana Kordek RN , Caroline Wagner BS , Lindsay Danley BS , Arvind Ramakrishnan BS , Hossein Daghagh MS , Yingwen Huang MS , Gaurav Dhapola MS , Aman Siddiqui BS, MBA , Sally Arai MD, MS , Sushma Bharadwaj MD , Saurabh Dahiya MD, FACP , Hany Elmariah MD , Matthew Frank MD, PhD , Hitomi Hosoya MD, PhD , Vanessa E Kennedy MD , Laura Johnston MD , Lori S. Muffly MD, MS","doi":"10.1016/j.jtct.2025.12.047","DOIUrl":"10.1016/j.jtct.2025.12.047","url":null,"abstract":"<div><h3>Background</h3><div>High-risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) remains difficult to cure in adults despite autologous CAR T cells or allogeneic hematopoietic cell transplant (HCT). Building on preclinical work showing CAR T cell safety post-HCT (Ghosh A, Smith M <em>Nature Medicine</em> 2017), we tested whether allogeneic CAR-T cells combined with myeloablative graft-engineered HCT (Orca-T) could enhance antileukemic activity without increasing GVHD or graft failure. We now report final clinical outcomes from this Phase 1 trial (NCT05507827).</div></div><div><h3>Methods</h3><div>This single-center trial tested allogeneic anti-CD19/CD22 CAR T cells combined with myeloablative conditioning and Orca-T (D0 HSPCs/Tregs; D+2 Tcons, per Meyer <em>Blood</em> 2025) in adults with HR B-ALL. Donor-derived CAR T cells were administered on D+2, tacrolimus began on D+3. The primary endpoint was engraftment without grade 3+ acute GVHD at D+42; secondary endpoints included survival outcomes, CAR persistence, and immune reconstitution.</div></div><div><h3>Results</h3><div>Eighteen patients (pts) enrolled between Sept 2022 and May 2025; 16 received both Orca-T and allogeneic CAR T cells; 1 received only Orca-T due to active infection at time of planned CAR T infusion and 1 did not proceed on trial. Median age was 31 years (range, 21–58); 70% were Hispanic, 76% were MRD+ post-induction. Most (76%) received matched sibling grafts; 24% were from matched unrelated donors. All pts have now reached the primary endpoint: engraftment occurred in 100% and no pts have developed 3+ acute GVHD. Acute GVHD occurred in 1 pt (grade 1) and chronic GVHD in 2 pts (1 mild; 1 moderate). There were no high-grade CAR mediated toxicities.</div><div>With median follow-up of 14 months (range, 3-35), disease-free and overall survival are both 100% (Figure 1A, 1B). Figure 1C depicts pre-and post-treatment MRD. Following allogeneic CAR T plus Orca-T, all pts achieved MRD clearance by flow cytometry (10-4) and remain undetectable to date. Two pts with pre-treatment MRD have ongoing detectable MRD by clonoSEQ (10-6) without evidence of relapse. Median time to peak CAR expansion was 13 days. Median circulating CAR T cells at peak expansion was 1,205 copies/100ng DNA, with a median D0-28 AUC of 13,324 copies/100ng DNA. <strong>Figure 2</strong> shows ongoing CAR detection by qPCR (LOD 10 copies/100ng DNA) averaged across patients; only 4 pts have evidence of functional B cell recovery.</div></div><div><h3>Conclusion</h3><div>Here, we report final safety and anti-tumor activity of the combination of allogeneic anti-CD19/CD22 CAR T cells with a myeloablative graft-engineered HCT in pts with HR B-ALL. This paradigm-shifting combination of CAR T and HCT resulted in 100% DFS without graft failure, significant GVHD, or severe CAR-mediated toxicity. We hypothesize this is due to tolerance for CAR molecules, resulting in persistent CAR expression and improved antitumor activity.","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S27"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.054
Shambavi Richard MD , Mahmoud Gaballa MMBCh , Tara Gregory MD , Saurabh Chhabra MD, MS , Larry D. Anderson Jr. MD, PhD , Luciano J. Costa MD, PhD , Caitlin Costello MD , Scott R. Goldsmith MD , Doris K. Hansen MD , Sridevi Rajeeve MD , Shaji Kumar MD , Dr. Aravind Ramakrishnan MD , Minoo Battiwalla MD, MS , Ajay K. Nooka MD, MPH , Hira Shaikh MBBS , Meiyue G. Hong MD , Steven Wang MS , Patricia Cheung PhD , Liang Li PhD , Binod Dhakal MD
<div><h3>Introduction</h3><div>Multiple myeloma (MM) accounts for nearly 20% of all hematologic cancers in the US and remains a substantial clinical burden. While BCMA-directed CAR T-cell therapy has improved outcomes, challenges persist. AZD0120 (formerly GC012F) is a first-in-class autologous BCMA/CD19 dual-targeting CAR T-cell therapy using the FasTCAR rapid manufacturing platform. We report preliminary phase 1b results from DURGA-1, an ongoing phase 1b/2 trial evaluating AZD0120 in patients (pts) with relapsed/refractory (RR) MM.</div></div><div><h3>Methods</h3><div>This open-label, single-arm, US-based, multicenter study (NCT05850234) evaluated the safety of 2 dose levels (DLs) of AZD0120. Eligible pts were ≥18 y with RRMM (3+ prior lines of therapy [pLOT]), ECOG PS 0–1, and evidence of progressive disease. Prior BCMA-directed therapy ≥6 mo with best response of partial response or better was permitted. Pts received a single infusion of AZD0120 (DL1: 1×10<sup>5</sup> cells/kg; DL2: 3×10<sup>5</sup> cells/kg). Phase 1b primary objectives: safety/tolerability, RP2D determination; secondary objectives: efficacy, cellular kinetics (CK), pharmacodynamics.</div></div><div><h3>Results</h3><div>At data cutoff (DCO; 18 July 2025), 25 pts received AZD0120 (n=12 DL1; n=13 DL2). Median age was 64 y (range 44–78), median pLOT was 4 (range 3–7), 72% were triple-class refractory, 20% had prior BCMA CAR T-cell therapy, and 28% had high-risk cytogenetic features. Median time from apheresis to infusion was 28 d (range 19–44); 5 pts received bridging therapy. Median follow-up was 1.4 mo (range 0–19.3). No dose-limiting toxicities were reported. Most common treatment-emergent AEs (any grade) were CRS (64%), neutrophil count decreased (56%), and anemia (32%). CRS was reported in 75% (DL1) and 54% (DL2) of pts, with no cases grade ≥3. Median time to CRS onset (DL1/DL2) was 9 d (range 2–11); 12 pts (48%) received tocilizumab to manage CRS. No deaths or cases of ICANSEC-colitis, or secondary primary malignancies were reported. For efficacy-evaluable pts (n=15), overall response rate was 100% and complete response rate was 33%; median time to response was 0.9 mo for both DLs (range 0.6–1.9). All pts evaluable for minimal residual disease (MRD; n=5 DL1; n=3 DL2; DCO 1 July 2025) were MRD negative by next-generation sequencing (10<sup>-5</sup> sensitivity). Three pts in DL1 with ≥12 mo follow-up maintained MRD negativity. CK analysis from 16 evaluable pts (DCO 12 June 2025) demonstrated median T<sub>max</sub> of 13 d post-infusion and median persistence of 42 d (range 13–273). Updated clinical data will be presented.</div></div><div><h3>Conclusion</h3><div>Preliminary phase 1b results demonstrated AZD0120 was well tolerated, with a low incidence of serious AEs, no grade ≥3 CRS, and no ICANS. FasTCAR-manufactured AZD0120 had controlled in vivo expansion leading to a predictable safety profile. A single infusion of AZD0120 achieved early, deep responses with 100% MRD ne
{"title":"Safety and Efficacy of AZD0120, a BCMA/CD19 Dual-Targeting CAR T-cell Therapy, in relapsed/refractory Multiple Myeloma: Preliminary Results from the DURGA-1 phase 1b/2 Study","authors":"Shambavi Richard MD , Mahmoud Gaballa MMBCh , Tara Gregory MD , Saurabh Chhabra MD, MS , Larry D. Anderson Jr. MD, PhD , Luciano J. Costa MD, PhD , Caitlin Costello MD , Scott R. Goldsmith MD , Doris K. Hansen MD , Sridevi Rajeeve MD , Shaji Kumar MD , Dr. Aravind Ramakrishnan MD , Minoo Battiwalla MD, MS , Ajay K. Nooka MD, MPH , Hira Shaikh MBBS , Meiyue G. Hong MD , Steven Wang MS , Patricia Cheung PhD , Liang Li PhD , Binod Dhakal MD","doi":"10.1016/j.jtct.2025.12.054","DOIUrl":"10.1016/j.jtct.2025.12.054","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple myeloma (MM) accounts for nearly 20% of all hematologic cancers in the US and remains a substantial clinical burden. While BCMA-directed CAR T-cell therapy has improved outcomes, challenges persist. AZD0120 (formerly GC012F) is a first-in-class autologous BCMA/CD19 dual-targeting CAR T-cell therapy using the FasTCAR rapid manufacturing platform. We report preliminary phase 1b results from DURGA-1, an ongoing phase 1b/2 trial evaluating AZD0120 in patients (pts) with relapsed/refractory (RR) MM.</div></div><div><h3>Methods</h3><div>This open-label, single-arm, US-based, multicenter study (NCT05850234) evaluated the safety of 2 dose levels (DLs) of AZD0120. Eligible pts were ≥18 y with RRMM (3+ prior lines of therapy [pLOT]), ECOG PS 0–1, and evidence of progressive disease. Prior BCMA-directed therapy ≥6 mo with best response of partial response or better was permitted. Pts received a single infusion of AZD0120 (DL1: 1×10<sup>5</sup> cells/kg; DL2: 3×10<sup>5</sup> cells/kg). Phase 1b primary objectives: safety/tolerability, RP2D determination; secondary objectives: efficacy, cellular kinetics (CK), pharmacodynamics.</div></div><div><h3>Results</h3><div>At data cutoff (DCO; 18 July 2025), 25 pts received AZD0120 (n=12 DL1; n=13 DL2). Median age was 64 y (range 44–78), median pLOT was 4 (range 3–7), 72% were triple-class refractory, 20% had prior BCMA CAR T-cell therapy, and 28% had high-risk cytogenetic features. Median time from apheresis to infusion was 28 d (range 19–44); 5 pts received bridging therapy. Median follow-up was 1.4 mo (range 0–19.3). No dose-limiting toxicities were reported. Most common treatment-emergent AEs (any grade) were CRS (64%), neutrophil count decreased (56%), and anemia (32%). CRS was reported in 75% (DL1) and 54% (DL2) of pts, with no cases grade ≥3. Median time to CRS onset (DL1/DL2) was 9 d (range 2–11); 12 pts (48%) received tocilizumab to manage CRS. No deaths or cases of ICANSEC-colitis, or secondary primary malignancies were reported. For efficacy-evaluable pts (n=15), overall response rate was 100% and complete response rate was 33%; median time to response was 0.9 mo for both DLs (range 0.6–1.9). All pts evaluable for minimal residual disease (MRD; n=5 DL1; n=3 DL2; DCO 1 July 2025) were MRD negative by next-generation sequencing (10<sup>-5</sup> sensitivity). Three pts in DL1 with ≥12 mo follow-up maintained MRD negativity. CK analysis from 16 evaluable pts (DCO 12 June 2025) demonstrated median T<sub>max</sub> of 13 d post-infusion and median persistence of 42 d (range 13–273). Updated clinical data will be presented.</div></div><div><h3>Conclusion</h3><div>Preliminary phase 1b results demonstrated AZD0120 was well tolerated, with a low incidence of serious AEs, no grade ≥3 CRS, and no ICANS. FasTCAR-manufactured AZD0120 had controlled in vivo expansion leading to a predictable safety profile. A single infusion of AZD0120 achieved early, deep responses with 100% MRD ne","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S33"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.072
Bonnie YeungLuk PhD , Yiouli P. Ktena MD , Margarita Dionysiou MD , Azeb Haile MS , Sarah Watt MD , Samara P Singh PhD , Anant Mashalkar Student , Johanna Tenaglia Student , Brianna Lee Student , Dheeksha Sudhakar BS , Ethan Sherman Student , Kenneth R. Cooke MD
<div><h3>Background</h3><div>Idiopathic pneumonia syndrome (IPS) is a major noninfectious lung complication following allogeneic bone marrow transplantation (AlloBMT). It arises from endothelial cell (EC) activation and injury, resulting in vascular leak and immune cell infiltration into the lung. The angiopoietin (Ang)-Tie2 signaling pathway plays a central role in regulating vascular integrity: Ang-1 stabilizes blood vessels and maintains EC quiescence, while Ang-2 acts as a functional antagonist, disrupting Tie2 signaling, promoting vascular permeability, and sensitizing ECs to inflammatory cytokines like TNFα. We hypothesize that dysregulation of the Ang:Tie2 axis drives EC dysfunction, inflammation, and lung injury characteristic of IPS.</div></div><div><h3>Methods</h3><div>We interrogated the proteome of blood samples from patients with IPS. Clinical insights were brought back to the bench using established murine BMT models.</div></div><div><h3>Results</h3><div>Antibody microarrays revealed that IPS patients had significant elevations in plasma TNFα and EC activation markers, including Ang-2 VCAM-1 and E-selectin. ELISA confirmed markedly increased Ang-2 and decreased Ang-1 at IPS onset compared with baseline and with uncomplicated BMT recipients. Importantly, Ang-2 levels decreased and Ang-1 levels normalized in patients responding to treatment, whereas both remained abnormal in those with progressive disease, indicating their biomarker potential for IPS activity and response.</div><div>Preclinical studies using a B6->F1 BMT model demonstrated elevated Ang2 mRNA and protein expression as early as day7 post AlloBMT, persisting through day14. Western blots on whole lung lysates (D14) showed down regulation of phospho-Tie2, PI3K, and Akt consistent with Ang2-mediated control of Tie2 signaling (Fig1). To determine therapeutic relevance, AlloBMT recipients were treated with the Ang-2 blocking antibody L1-10 (Amgen) subQ from day -1 through day+42. Compared to saline-treated controls, L1-10 treated mice exhibited significantly reduced bronchoalveolar lavage cellularity, CD4+, CD8+T-cell, and macrophage infiltration and lower lung pathology scores. Functionally, L1-10 treatment led to significant improvements in pulmonary physiology. Early blockade of Ang2 signaling also decreased EC apoptosis at D7 post BMT as evidenced by reduced annexin V and caspase 3/7 staining (Fig2). Notably, TNFa enhances Ang2, IL-6, and adhesion molecule gene expression while reducing EC resistance and increasing EC permeability in a novel ex vivo EC system (Fig3).</div></div><div><h3>Conclusions</h3><div>Elevated Ang-2 and suppressed Ang-1 signaling disrupts EC stability, amplifying cytokine sensitivity and lung injury. These results identify the Ang2 axis as a pivotal regulator of TNFa mediated EC activation, permeability, and immune driven inflammation in IPS, and highlight Ang-2 inhibition as a promising therapeutic strategy for this life-threatening complication
{"title":"The Ang2:Tie2 Axis Regulates Pulmonary Vascular Endothelial Cell Injury and Activation Responsible for the Development of Idiopathic Pneumonia Syndrome Following Allogeneic Blood and Marrow Transplantation","authors":"Bonnie YeungLuk PhD , Yiouli P. Ktena MD , Margarita Dionysiou MD , Azeb Haile MS , Sarah Watt MD , Samara P Singh PhD , Anant Mashalkar Student , Johanna Tenaglia Student , Brianna Lee Student , Dheeksha Sudhakar BS , Ethan Sherman Student , Kenneth R. Cooke MD","doi":"10.1016/j.jtct.2025.12.072","DOIUrl":"10.1016/j.jtct.2025.12.072","url":null,"abstract":"<div><h3>Background</h3><div>Idiopathic pneumonia syndrome (IPS) is a major noninfectious lung complication following allogeneic bone marrow transplantation (AlloBMT). It arises from endothelial cell (EC) activation and injury, resulting in vascular leak and immune cell infiltration into the lung. The angiopoietin (Ang)-Tie2 signaling pathway plays a central role in regulating vascular integrity: Ang-1 stabilizes blood vessels and maintains EC quiescence, while Ang-2 acts as a functional antagonist, disrupting Tie2 signaling, promoting vascular permeability, and sensitizing ECs to inflammatory cytokines like TNFα. We hypothesize that dysregulation of the Ang:Tie2 axis drives EC dysfunction, inflammation, and lung injury characteristic of IPS.</div></div><div><h3>Methods</h3><div>We interrogated the proteome of blood samples from patients with IPS. Clinical insights were brought back to the bench using established murine BMT models.</div></div><div><h3>Results</h3><div>Antibody microarrays revealed that IPS patients had significant elevations in plasma TNFα and EC activation markers, including Ang-2 VCAM-1 and E-selectin. ELISA confirmed markedly increased Ang-2 and decreased Ang-1 at IPS onset compared with baseline and with uncomplicated BMT recipients. Importantly, Ang-2 levels decreased and Ang-1 levels normalized in patients responding to treatment, whereas both remained abnormal in those with progressive disease, indicating their biomarker potential for IPS activity and response.</div><div>Preclinical studies using a B6->F1 BMT model demonstrated elevated Ang2 mRNA and protein expression as early as day7 post AlloBMT, persisting through day14. Western blots on whole lung lysates (D14) showed down regulation of phospho-Tie2, PI3K, and Akt consistent with Ang2-mediated control of Tie2 signaling (Fig1). To determine therapeutic relevance, AlloBMT recipients were treated with the Ang-2 blocking antibody L1-10 (Amgen) subQ from day -1 through day+42. Compared to saline-treated controls, L1-10 treated mice exhibited significantly reduced bronchoalveolar lavage cellularity, CD4+, CD8+T-cell, and macrophage infiltration and lower lung pathology scores. Functionally, L1-10 treatment led to significant improvements in pulmonary physiology. Early blockade of Ang2 signaling also decreased EC apoptosis at D7 post BMT as evidenced by reduced annexin V and caspase 3/7 staining (Fig2). Notably, TNFa enhances Ang2, IL-6, and adhesion molecule gene expression while reducing EC resistance and increasing EC permeability in a novel ex vivo EC system (Fig3).</div></div><div><h3>Conclusions</h3><div>Elevated Ang-2 and suppressed Ang-1 signaling disrupts EC stability, amplifying cytokine sensitivity and lung injury. These results identify the Ang2 axis as a pivotal regulator of TNFa mediated EC activation, permeability, and immune driven inflammation in IPS, and highlight Ang-2 inhibition as a promising therapeutic strategy for this life-threatening complication","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S45-S46"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.070
Van Anh Do-Thi PhD , Jathniel Hernandez BS , Emma Bratch BS , Pavan Reddy MD , Daniel Peltier MD, PhD
<div><div>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often complicated by acute graft-versus-host disease (aGVHD), a potentially life-threatening condition driven by donor allo-reactive T cells. Mechanisms regulating allo-T cell function remain incompletely understood. Emerging evidence suggests that noncanonical microproteins (<100 amino acids) act as cell type-specific immune regulators, yet their roles in T cell-intrinsic function are largely unknown.</div><div>Noncanonical microproteins are frequently encoded by long noncoding RNAs (lncRNAs) with ribosomal access (i.e. cytoplasmic). These lncRNA-encoded microproteins can function independent of their parent transcripts, creating “bifunctional” genes whose RNA and protein products may act concordantly or separately.</div><div>We previously identified a T cell-specific lncRNA, <em>ReLoT/LINC00402</em>, as a biomarker for aGVHD (Peltier et al., <em>Sci. Transl. Med.</em>, 2021). Because <em>ReLoT</em> is cytoplasmic, we performed an <em>in vitro</em> transcription-translation assay, revealing a 10 kDa microprotein. Translation prediction algorithms identified a small open reading frame (sORF) near the 5′ end of <em>ReLoT</em> consistent with this size. Using deletion and frameshift mutants and a custom polyclonal antibody, we confirmed that this sORF encodes the 90-amino acid <em>ReLoT</em> microprotein. When ectopically expressed in Jurkat T cells, the microprotein localized to cytoplasmic and mitochondrial compartments and was detected endogenously in primary human T cells.</div><div>To dissect RNA- versus microprotein-dependent functions, we overexpressed <em>ReLoT</em> mutants enabling either or both activities in Jurkat T cells lacking endogenous <em>ReLoT</em>. Both the lncRNA and microprotein independently suppressed IL-2 production after T cell receptor activation (p<0.01), without affecting ERK phosphorylation, suggesting cooperative inhibition of IL-2.</div><div>We next introduced these constructs into primary murine T cells via lentiviral transduction of hematopoietic stem cells, followed by adoptive transfer into congenic mice. Naïve T cell proliferation in response to anti-CD3/CD28 stimulation was microprotein-dependent (p<0.05), and Ki67 expression was reduced in splenic T cells following allo-HSCT using donor T cells expressing microprotein-only constructs (p<0.05). Conversely, CRISPR/Cas9 disruption of the sORF in human T cells increased proliferation (p<0.01).</div><div>In an MHC-mismatched (B6→BALB/c) murine aGVHD model, recipients of T cells expressing microprotein-only constructs exhibited reduced mortality and clinical scores (mortality p=0.01; score p=0.007), with similar trends for RNA-only constructs (mortality p=0.06; score p=0.06).</div><div>These findings establish <em>ReLoT</em> as a bifunctional, T cell-intrinsic regulator of alloimmunity. Modulating either the <em>ReLoT</em> RNA or its microprotein may offer a novel strategy to
{"title":"A Long Noncoding RNA-Encoded Noncanonical Microprotein Regulates Allogeneic T cell-Driven Acute Graft-Versus-Host Disease","authors":"Van Anh Do-Thi PhD , Jathniel Hernandez BS , Emma Bratch BS , Pavan Reddy MD , Daniel Peltier MD, PhD","doi":"10.1016/j.jtct.2025.12.070","DOIUrl":"10.1016/j.jtct.2025.12.070","url":null,"abstract":"<div><div>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often complicated by acute graft-versus-host disease (aGVHD), a potentially life-threatening condition driven by donor allo-reactive T cells. Mechanisms regulating allo-T cell function remain incompletely understood. Emerging evidence suggests that noncanonical microproteins (<100 amino acids) act as cell type-specific immune regulators, yet their roles in T cell-intrinsic function are largely unknown.</div><div>Noncanonical microproteins are frequently encoded by long noncoding RNAs (lncRNAs) with ribosomal access (i.e. cytoplasmic). These lncRNA-encoded microproteins can function independent of their parent transcripts, creating “bifunctional” genes whose RNA and protein products may act concordantly or separately.</div><div>We previously identified a T cell-specific lncRNA, <em>ReLoT/LINC00402</em>, as a biomarker for aGVHD (Peltier et al., <em>Sci. Transl. Med.</em>, 2021). Because <em>ReLoT</em> is cytoplasmic, we performed an <em>in vitro</em> transcription-translation assay, revealing a 10 kDa microprotein. Translation prediction algorithms identified a small open reading frame (sORF) near the 5′ end of <em>ReLoT</em> consistent with this size. Using deletion and frameshift mutants and a custom polyclonal antibody, we confirmed that this sORF encodes the 90-amino acid <em>ReLoT</em> microprotein. When ectopically expressed in Jurkat T cells, the microprotein localized to cytoplasmic and mitochondrial compartments and was detected endogenously in primary human T cells.</div><div>To dissect RNA- versus microprotein-dependent functions, we overexpressed <em>ReLoT</em> mutants enabling either or both activities in Jurkat T cells lacking endogenous <em>ReLoT</em>. Both the lncRNA and microprotein independently suppressed IL-2 production after T cell receptor activation (p<0.01), without affecting ERK phosphorylation, suggesting cooperative inhibition of IL-2.</div><div>We next introduced these constructs into primary murine T cells via lentiviral transduction of hematopoietic stem cells, followed by adoptive transfer into congenic mice. Naïve T cell proliferation in response to anti-CD3/CD28 stimulation was microprotein-dependent (p<0.05), and Ki67 expression was reduced in splenic T cells following allo-HSCT using donor T cells expressing microprotein-only constructs (p<0.05). Conversely, CRISPR/Cas9 disruption of the sORF in human T cells increased proliferation (p<0.01).</div><div>In an MHC-mismatched (B6→BALB/c) murine aGVHD model, recipients of T cells expressing microprotein-only constructs exhibited reduced mortality and clinical scores (mortality p=0.01; score p=0.007), with similar trends for RNA-only constructs (mortality p=0.06; score p=0.06).</div><div>These findings establish <em>ReLoT</em> as a bifunctional, T cell-intrinsic regulator of alloimmunity. Modulating either the <em>ReLoT</em> RNA or its microprotein may offer a novel strategy to ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S44-S45"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.093
Nosha Farhadfar MD , Brent R Logan PhD , Naya He MPH , Joseph A. Pidala MD, PhD , Heather J. Symons MD , Jason Dehn MPH , Asad Bashey MD, PhD , Steven M Devine MD , Michael R. Grunwald MD , Brandon Hayes-Lattin MD , William J. Hogan MB, BCh , Eric Leifer PhD , Peter Westervelt MD , Stefan O. Ciurea MD , Mary M. Horowitz MD, MS , Stephanie J. Lee MD, MPH , Bronwen E. Shaw MD, PhD
Introduction
Quality of life (QoL) is a critical indicator of therapeutic benefit and long-term recovery after allogeneic hematopoietic cell transplantation (HCT). BMT CTN 1702 trial (NCT03904134), a multicenter study (2019-2022) evaluating donor search, selection practices and outcomes of HCT using alternative donor sources, incorporated QoL as a secondary endpoint.
Objectives
The aim of the QoL sub-study was to explore the long-term QoL in a more homogenous subset of patients with AML/ALL in CR1/early stage MDS who provided additional clinical and patient-reported outcomes (PRO) data and compare those receiving MUD or Haplo donors.
Methods
QoL was assessed using PROMIS measures and Lee Symptom Scale (LSS). PROs were completed at baseline, 1 and 2 years post-HCT. PRO analysis was done using a generalized estimating equation linear regression model with an independent working covariance matrix to model the mean PRO outcome at each time point. Late effects, infection rates, and healthcare utilization were also compared. Statistical significance was defined as p-value ≤ 0.01.
Results
304 patients were analyzed (61 Haplo and 243 MUD). Some characteristics differed at baseline (Table 1), but consistent with findings from the parent study. No significant differences were observed in any clinical outcomes including Graft versus Host Disease (GvHD) or GVHD-free survival (GRFS). While PRO submission rates at baseline were similar (MUD 67%, Haplo 64%), retention in the MUD cohort was higher than Haplo (80% and 83% vs. 58% and 60% at year 1, at year 2, respectively). In univariate analysis, there was no significant difference in median PROs score between the two cohorts at any timepoint. Similarly, in multivariable analysis, there were no significant differences in post-HCT trajectory of QoL domains. No significant differences in late effects including pulmonary, cardiac, or renal complications were observed. The use of Haplo donors were associated with significantly more hospital days (median days 27.0 vs. 21.0, p<0.01) and viral infections (49.2% vs. 31.8%, p=0.01) in the first 100 days.
Conclusion
Despite similar QoL trajectories, the increased hospital days and viral infections in Haplo HCT may reflect differences in post-transplant burden, possible associated with the treatment strategy. These findings suggest that QoL data meaningfully inform donor selection and long-term care strategies.
生活质量（QoL）是异体造血细胞移植（HCT）后治疗效果和长期恢复的重要指标。BMT CTN 1702试验（NCT03904134）是一项多中心研究（2019-2022），评估使用替代供体来源的HCT供体搜索、选择实践和结果，将生活质量作为次要终点。生活质量亚研究的目的是探索更同质的CR1/早期MDS AML/ALL患者的长期生活质量，这些患者提供了额外的临床和患者报告的结果（PRO）数据，并比较接受MUD或Haplo供体的患者。方法采用PROMIS量表和Lee症状量表（LSS）进行满意度评价。在hct后的基线、1年和2年完成PROs。PRO分析采用广义估计方程线性回归模型，采用独立工作协方差矩阵对每个时间点的平均PRO结果进行建模。后期效应、感染率和医疗保健利用率也进行了比较。统计学意义定义为p值≤0.01。结果共分析304例患者（Haplo 61例，MUD 243例）。一些特征在基线时有所不同（表1），但与母体研究的结果一致。在包括移植物抗宿主病（GvHD）或无GvHD生存（GRFS）在内的任何临床结果中均未观察到显著差异。虽然基线时PRO提交率相似（MUD 67%, Haplo 64%），但MUD队列的保留率高于Haplo（第一年和第二年分别为80%和83%，第二年分别为58%和60%）。在单变量分析中，两个队列在任何时间点的pro评分中位数均无显著差异。同样，在多变量分析中，hct后生活质量域的轨迹没有显著差异。包括肺、心脏或肾脏并发症在内的晚期效应未观察到显著差异。使用Haplo供体与前100天住院天数（中位天数27.0 vs. 21.0, p=0.01）和病毒感染（49.2% vs. 31.8%, p=0.01）显著增加相关。结论：尽管生活质量轨迹相似，但Haplo HCT患者住院天数和病毒感染增加可能反映了移植后负担的差异，这可能与治疗策略有关。这些发现表明，生活质量数据对供体选择和长期护理策略有意义。
{"title":"Quality of Life and Late Effects Following Haploidentical Vs. Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantation: Secondary Analysis of BMT CTN 1702","authors":"Nosha Farhadfar MD , Brent R Logan PhD , Naya He MPH , Joseph A. Pidala MD, PhD , Heather J. Symons MD , Jason Dehn MPH , Asad Bashey MD, PhD , Steven M Devine MD , Michael R. Grunwald MD , Brandon Hayes-Lattin MD , William J. Hogan MB, BCh , Eric Leifer PhD , Peter Westervelt MD , Stefan O. Ciurea MD , Mary M. Horowitz MD, MS , Stephanie J. Lee MD, MPH , Bronwen E. Shaw MD, PhD","doi":"10.1016/j.jtct.2025.12.093","DOIUrl":"10.1016/j.jtct.2025.12.093","url":null,"abstract":"<div><h3>Introduction</h3><div>Quality of life (QoL) is a critical indicator of therapeutic benefit and long-term recovery after allogeneic hematopoietic cell transplantation (HCT). BMT CTN 1702 trial (NCT03904134), a multicenter study (2019-2022) evaluating donor search, selection practices and outcomes of HCT using alternative donor sources, incorporated QoL as a secondary endpoint.</div></div><div><h3>Objectives</h3><div>The aim of the QoL sub-study was to explore the long-term QoL in a more homogenous subset of patients with AML/ALL in CR1/early stage MDS who provided additional clinical and patient-reported outcomes (PRO) data and compare those receiving MUD or Haplo donors.</div></div><div><h3>Methods</h3><div>QoL was assessed using PROMIS measures and Lee Symptom Scale (LSS). PROs were completed at baseline, 1 and 2 years post-HCT. PRO analysis was done using a generalized estimating equation linear regression model with an independent working covariance matrix to model the mean PRO outcome at each time point. Late effects, infection rates, and healthcare utilization were also compared. Statistical significance was defined as p-value ≤ 0.01.</div></div><div><h3>Results</h3><div>304 patients were analyzed (61 Haplo and 243 MUD). Some characteristics differed at baseline (Table 1), but consistent with findings from the parent study. No significant differences were observed in any clinical outcomes including Graft versus Host Disease (GvHD) or GVHD-free survival (GRFS). While PRO submission rates at baseline were similar (MUD 67%, Haplo 64%), retention in the MUD cohort was higher than Haplo (80% and 83% vs. 58% and 60% at year 1, at year 2, respectively). In univariate analysis, there was no significant difference in median PROs score between the two cohorts at any timepoint. Similarly, in multivariable analysis, there were no significant differences in post-HCT trajectory of QoL domains. No significant differences in late effects including pulmonary, cardiac, or renal complications were observed. The use of Haplo donors were associated with significantly more hospital days (median days 27.0 vs. 21.0, p<0.01) and viral infections (49.2% vs. 31.8%, p=0.01) in the first 100 days.</div></div><div><h3>Conclusion</h3><div>Despite similar QoL trajectories, the increased hospital days and viral infections in Haplo HCT may reflect differences in post-transplant burden, possible associated with the treatment strategy. These findings suggest that QoL data meaningfully inform donor selection and long-term care strategies.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S62"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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