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.
{"title":"Long-Term Cardiac Function Remains Stable to Improved Following Curative Allogeneic Hematopoietic Cell Transplantation for Pediatric Sickle Cell Disease: A STAR Analysis","authors":"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","doi":"10.1016/j.jtct.2025.12.091","DOIUrl":"10.1016/j.jtct.2025.12.091","url":null,"abstract":"<div><div>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.</div><div>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.</div><div>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.</div><div>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.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S60-S61"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098793","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/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.2025.09.043
Jingjing Lan , Yulan Qiu , Mengmeng Teng , Chao Meng , Dan Sun , Ziyuan Ma , Shiqi Cheng , Xiaoning Wang , Juan Ren , Siying Chen , Yalin Dong
<div><div>Letermovir (LMV) is vital for cytomegalovirus prevention in transplant recipients, but its safety and drug–drug interactions (DDI) related adverse event (AE) risks require further investigation. This study conducted a pharmacovigilance analysis to identify novel AE signals of LMV and assess DDI-related AEs with commonly co-administered drugs. AE reports from 29 quarters, from the launch of LMV to the fourth quarter of 2024, were collected from the Food and Drug Administration Adverse Event Reporting System for analysis. Two statistical models (reporting odds ratio [ROR] method and medicines and healthcare products regulatory agency) were used to identify AEs meeting the threshold, which were then compared with LMV drug labels and designated medical event (DME) risk signals. Four models were applied to detect potential AE signals related to LMV combination use, and DDI-related AEs and DMEs were analyzed in conjunction with single-drug mining results. Finally, 54 LMV AE signals were identified, of which 4 AE signals had appeared in the LMV drug labels, namely edema (ROR = 3.69), acute heart failure (ROR = 14.48), pericardial effusion (ROR = 4.77), and atrial fibrillation (ROR = 3.61). Among the remaining new AE signals, AEs with stronger ROR values included herpetic gastritis (ROR = 23,772.49), human herpesvirus 6 encephalitis (ROR = 214.17), and acute graft-versus-host disease (aGVHD) in skin (ROR = 190.2). Eight DME signals of LMV were determined, such as hepatic failure, drug-induced liver injury, renal failure, and acute kidney injury (AKI). In the DDI analysis, 279 DDI-related AE signals meeting all four model criteria were identified. Among 28 drugs commonly co-administered with LMV, immunomodulatory agents contributed the highest proportion of signals (34.4%, 96/279), with cyclosporine associated with the most AE types (10.4%, 29/279). The most frequent AEs included aplastic anemia (4.3%), esophagitis (3.9%), and renal failure (3.6%). There was a positive AE signal difference when LMV was combined with cyclosporine or tacrolimus. When used in combination with cyclosporine, in addition to cardiac events and peripheral edema listed in the LMV drug label, DME signals such as pancytopenia, febrile neutropenia, AKI, and hepatic failure may also occur; when used in combination with tacrolimus, one needs to be alert to the occurrence of aGVHD in skin/intestine. LMV use may induce cardiac AE signals such as acute heart failure, pericardial effusion, and atrial fibrillation, and may increase the risk of herpes virus reactivation. When LMV is used in combination with drugs such as cyclosporine or tacrolimus, it may exacerbate hepatic and renal toxicity. Acute heart failure and atrial fibrillation AE signals were detected when combined with cyclosporine. Future efforts should focus on the safety of LMV in clinical practice and real-world settings, with optimized medication strategies to minimize risks and enhance therapeutic outcomes.</div></
{"title":"Mining Safety Signals of Letermovir Drug Combinations: Real-World Pharmacovigilance Analysis","authors":"Jingjing Lan , Yulan Qiu , Mengmeng Teng , Chao Meng , Dan Sun , Ziyuan Ma , Shiqi Cheng , Xiaoning Wang , Juan Ren , Siying Chen , Yalin Dong","doi":"10.1016/j.jtct.2025.09.043","DOIUrl":"10.1016/j.jtct.2025.09.043","url":null,"abstract":"<div><div>Letermovir (LMV) is vital for cytomegalovirus prevention in transplant recipients, but its safety and drug–drug interactions (DDI) related adverse event (AE) risks require further investigation. This study conducted a pharmacovigilance analysis to identify novel AE signals of LMV and assess DDI-related AEs with commonly co-administered drugs. AE reports from 29 quarters, from the launch of LMV to the fourth quarter of 2024, were collected from the Food and Drug Administration Adverse Event Reporting System for analysis. Two statistical models (reporting odds ratio [ROR] method and medicines and healthcare products regulatory agency) were used to identify AEs meeting the threshold, which were then compared with LMV drug labels and designated medical event (DME) risk signals. Four models were applied to detect potential AE signals related to LMV combination use, and DDI-related AEs and DMEs were analyzed in conjunction with single-drug mining results. Finally, 54 LMV AE signals were identified, of which 4 AE signals had appeared in the LMV drug labels, namely edema (ROR = 3.69), acute heart failure (ROR = 14.48), pericardial effusion (ROR = 4.77), and atrial fibrillation (ROR = 3.61). Among the remaining new AE signals, AEs with stronger ROR values included herpetic gastritis (ROR = 23,772.49), human herpesvirus 6 encephalitis (ROR = 214.17), and acute graft-versus-host disease (aGVHD) in skin (ROR = 190.2). Eight DME signals of LMV were determined, such as hepatic failure, drug-induced liver injury, renal failure, and acute kidney injury (AKI). In the DDI analysis, 279 DDI-related AE signals meeting all four model criteria were identified. Among 28 drugs commonly co-administered with LMV, immunomodulatory agents contributed the highest proportion of signals (34.4%, 96/279), with cyclosporine associated with the most AE types (10.4%, 29/279). The most frequent AEs included aplastic anemia (4.3%), esophagitis (3.9%), and renal failure (3.6%). There was a positive AE signal difference when LMV was combined with cyclosporine or tacrolimus. When used in combination with cyclosporine, in addition to cardiac events and peripheral edema listed in the LMV drug label, DME signals such as pancytopenia, febrile neutropenia, AKI, and hepatic failure may also occur; when used in combination with tacrolimus, one needs to be alert to the occurrence of aGVHD in skin/intestine. LMV use may induce cardiac AE signals such as acute heart failure, pericardial effusion, and atrial fibrillation, and may increase the risk of herpes virus reactivation. When LMV is used in combination with drugs such as cyclosporine or tacrolimus, it may exacerbate hepatic and renal toxicity. Acute heart failure and atrial fibrillation AE signals were detected when combined with cyclosporine. Future efforts should focus on the safety of LMV in clinical practice and real-world settings, with optimized medication strategies to minimize risks and enhance therapeutic outcomes.</div></","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 211.e1-211.e13"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226148","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.2025.10.031
Hannah R. Abrams , Helene Starks , Lindsey Bandini , Terry Harrington , Mary-Elizabeth M. Percival , Roland B. Walter , Kathryn Russell , Raya Mawad , Jacob Appelbaum , Mohamed L. Sorror , Anna B. Halpern
Background
New disease indications and supportive care advances have expanded the populations who may benefit from cellular therapies, including autologous or allogeneic hematopoietic cell transplant (HCT) and/or chimeric antigen receptor T-cell therapy (CAR T). However, nonmedical requirements for these therapies, such as caregiver and housing availability, may limit access. We sought a detailed national assessment of nonmedical requirements for HCT and CAR T-cell therapy to describe and quantify barriers.
Objective
Describe the national landscape and implementation of logistical and nonmedical requirements for HCT and CAR T-cell therapy.
Study Design
We developed a web-based survey of HCT/CAR T-cell therapy requirements and obtained pilot feedback from 3 centers that regularly perform HCT/CAR T-cell therapy. We distributed the survey via the NCCN Best Practices Committee, which is composed of physician, nursing, and administrative leaders from 34 member institutions. We requested survey completion by an institutional content area expert.
Results
The response rate was 91% (31/34). >80% of centers required a caregiver, local housing, and local transportation, but the number of days required, institutional supports, and acceptable distances varied widely. A subset of centers offered "all-outpatient" procedures and required more stringent logistical criteria, including autologous HCT by 13/19 centers (68%), allogeneic HCT by 4/8 centers (50%), and CAR T-cell therapy by 10/16 centers (63%). Many centers excluded patients with a history of medication nonadherence, substance use, or psychiatric comorbidity, but most did not employ formal adjudication or definition of patient eligibility. Institutions noted “soft” contraindications or case-by-case review for these patients and those experiencing homelessness, lack of insurance, or without citizenship. Overall, caregiving, housing, cost, and insurance coverage emerged as the top nonmedical barriers to HCT and CAR T-cell therapy.
Conclusions
Significant variability exists in nonmedical requirements for HCT and CAR T-cell therapy, with a lack of standard policies across institutions. We recommend that centers formally track reasons for noneligibility to identify nonmedical barriers to HCT and CAR T-cell therapy and develop targeted interventions to reduce the number of patients who are excluded for nonmedical reasons.
{"title":"National Landscape of Logistical and Nonmedical Requirements for Transplantation and Cellular Therapy","authors":"Hannah R. Abrams , Helene Starks , Lindsey Bandini , Terry Harrington , Mary-Elizabeth M. Percival , Roland B. Walter , Kathryn Russell , Raya Mawad , Jacob Appelbaum , Mohamed L. Sorror , Anna B. Halpern","doi":"10.1016/j.jtct.2025.10.031","DOIUrl":"10.1016/j.jtct.2025.10.031","url":null,"abstract":"<div><h3>Background</h3><div>New disease indications and supportive care advances have expanded the populations who may benefit from cellular therapies, including autologous or allogeneic hematopoietic cell transplant (HCT) and/or chimeric antigen receptor T-cell therapy (CAR T). However, nonmedical requirements for these therapies, such as caregiver and housing availability, may limit access. We sought a detailed national assessment of nonmedical requirements for HCT and CAR T-cell therapy to describe and quantify barriers.</div></div><div><h3>Objective</h3><div>Describe the national landscape and implementation of logistical and nonmedical requirements for HCT and CAR T-cell therapy.</div></div><div><h3>Study Design</h3><div>We developed a web-based survey of HCT/CAR T-cell therapy requirements and obtained pilot feedback from 3 centers that regularly perform HCT/CAR T-cell therapy. We distributed the survey via the NCCN Best Practices Committee, which is composed of physician, nursing, and administrative leaders from 34 member institutions. We requested survey completion by an institutional content area expert.</div></div><div><h3>Results</h3><div>The response rate was 91% (31/34). >80% of centers required a caregiver, local housing, and local transportation, but the number of days required, institutional supports, and acceptable distances varied widely. A subset of centers offered \"all-outpatient\" procedures and required more stringent logistical criteria, including autologous HCT by 13/19 centers (68%), allogeneic HCT by 4/8 centers (50%), and CAR T-cell therapy by 10/16 centers (63%). Many centers excluded patients with a history of medication nonadherence, substance use, or psychiatric comorbidity, but most did not employ formal adjudication or definition of patient eligibility. Institutions noted “soft” contraindications or case-by-case review for these patients and those experiencing homelessness, lack of insurance, or without citizenship. Overall, caregiving, housing, cost, and insurance coverage emerged as the top nonmedical barriers to HCT and CAR T-cell therapy.</div></div><div><h3>Conclusions</h3><div>Significant variability exists in nonmedical requirements for HCT and CAR T-cell therapy, with a lack of standard policies across institutions. We recommend that centers formally track reasons for noneligibility to identify nonmedical barriers to HCT and CAR T-cell therapy and develop targeted interventions to reduce the number of patients who are excluded for nonmedical reasons.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 209.e1-209.e13"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453222","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}
Inflammatory bowel disease (IBD) is a phenotype of patients with inborn errors of immunity (IEI). Allogeneic hematopoietic cell transplantation (HCT) is an established curative treatment for IEI; however, the effect of IBD on HCT outcomes is unclear. We evaluated the impact of IBD on post-HCT prognosis in pediatric patients with IEI. We used the Japanese transplant registry database to retrospectively analyze the medical records of 625 patients with pediatric IEI who underwent allogeneic HCT between 2007 and 2022 to evaluate the clinical impact of IBD on these patients. Sixty-six (10.6%) patients had concurrent IBD before HCT. Compared with patients without IBD, those with IBD did not show inferior overall survival, transplant-related mortality, or neutrophil and platelet engraftment. Moreover, no significant differences were observed in the incidence of acute or chronic graft-versus-host disease (GVHD) between the two groups. However, the IBD group had a higher incidence of acute gastrointestinal GVHD. These findings remained consistent even after propensity score matching, accounting for the identified risk factors, including age at HCT, performance status, total HCT-specific comorbidity index score, HLA mismatch, era of HCT, and underlying disease classification. IBD has a limited effect on HCT outcomes in patients with pediatric IEI, despite the higher incidence of acute gastrointestinal GVHD. Nevertheless, in this study, we included patients with heterogeneous and complex disease backgrounds, indicating the need for further investigation to confirm the findings.
{"title":"Effect of Inflammatory Bowel Disease on Clinical Outcomes of Hematopoietic Cell Transplantation for Inborn Errors of Immunity","authors":"Ryu Yanagisawa , Satoshi Miyamoto , Yoji Sasahara , Michiko Kajiwara , Masataka Ishimura , Hirotoshi Sakaguchi , Takehiko Doi , Yoshiyuki Takahashi , Yuko Cho , Maho Sato , Saori Katayama , Katsuyoshi Koh , Masakatsu Yanagimachi , Daiichiro Hasegawa , Keiko Okada , Junko Takita , Shoji Saito , Atsushi Sato , Moeko Hino , Kimikazu Matsumoto , Katsutsugu Umeda","doi":"10.1016/j.jtct.2025.11.006","DOIUrl":"10.1016/j.jtct.2025.11.006","url":null,"abstract":"<div><div>Inflammatory bowel disease (IBD) is a phenotype of patients with inborn errors of immunity (IEI). Allogeneic hematopoietic cell transplantation (HCT) is an established curative treatment for IEI; however, the effect of IBD on HCT outcomes is unclear. We evaluated the impact of IBD on post-HCT prognosis in pediatric patients with IEI. We used the Japanese transplant registry database to retrospectively analyze the medical records of 625 patients with pediatric IEI who underwent allogeneic HCT between 2007 and 2022 to evaluate the clinical impact of IBD on these patients. Sixty-six (10.6%) patients had concurrent IBD before HCT. Compared with patients without IBD, those with IBD did not show inferior overall survival, transplant-related mortality, or neutrophil and platelet engraftment. Moreover, no significant differences were observed in the incidence of acute or chronic graft-versus-host disease (GVHD) between the two groups. However, the IBD group had a higher incidence of acute gastrointestinal GVHD. These findings remained consistent even after propensity score matching, accounting for the identified risk factors, including age at HCT, performance status, total HCT-specific comorbidity index score, HLA mismatch, era of HCT, and underlying disease classification. IBD has a limited effect on HCT outcomes in patients with pediatric IEI, despite the higher incidence of acute gastrointestinal GVHD. Nevertheless, in this study, we included patients with heterogeneous and complex disease backgrounds, indicating the need for further investigation to confirm the findings.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 203.e1-203.e11"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145507474","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.2025.10.003
Jae-Ho Yoon, Daehun Kwag, Gi June Min, Sung-Soo Park, Silvia Park, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication following hematopoietic cell transplantation (HCT), with a markedly poor prognosis in patients with severe or very severe presentations. Defibrotide (DF) is the sole approved treatment for severe to very severe VOD/SOS, but real-world evidence remains limited, particularly in East Asian populations. We retrospectively analyzed 73 adult patients with severe or very severe VOD/SOS treated with DF between 2016 and 2023 at a single tertiary center in Korea. Diagnosis and grading were based on the revised European Society for Blood and Marrow Transplantation criteria. During the study period, national reimbursement guidelines for DF evolved from requiring ≥4 of 6 severity criteria to ≥2 of 5 severity criteria, allowing earlier initiation of treatment. The median time from HCT to diagnosis of VOD/SOS was 24 days (range, 1 to 843 days), and DF was administered within a median of 1 day after diagnosis. At DF initiation, 40 patients were classified as severe and 33 were classified as very severe; disease progression resulted in 53 patients reaching the very severe category. The overall response rate was 46.5%, and complete resolution was achieved in 39.7% of cases. The 100-day overall survival was 34.2%, significantly higher in the patients receiving DF within 2 days of diagnosis (36.0% versus 17.4%; P = .049). High total bilirubin levels at diagnosis and at the worst disease period were strongly associated with poor long-term survival regardless of severity criteria. These data provide real-world support for the early use of DF and suggest the prognostic utility of total bilirubin level in guiding treatment for VOD/SOS following HCT.
{"title":"Real-World Outcome of Defibrotide Treatment for Severe Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation","authors":"Jae-Ho Yoon, Daehun Kwag, Gi June Min, Sung-Soo Park, Silvia Park, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho","doi":"10.1016/j.jtct.2025.10.003","DOIUrl":"10.1016/j.jtct.2025.10.003","url":null,"abstract":"<div><div>Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication following hematopoietic cell transplantation (HCT), with a markedly poor prognosis in patients with severe or very severe presentations. Defibrotide (DF) is the sole approved treatment for severe to very severe VOD/SOS, but real-world evidence remains limited, particularly in East Asian populations. We retrospectively analyzed 73 adult patients with severe or very severe VOD/SOS treated with DF between 2016 and 2023 at a single tertiary center in Korea. Diagnosis and grading were based on the revised European Society for Blood and Marrow Transplantation criteria. During the study period, national reimbursement guidelines for DF evolved from requiring ≥4 of 6 severity criteria to ≥2 of 5 severity criteria, allowing earlier initiation of treatment. The median time from HCT to diagnosis of VOD/SOS was 24 days (range, 1 to 843 days), and DF was administered within a median of 1 day after diagnosis. At DF initiation, 40 patients were classified as severe and 33 were classified as very severe; disease progression resulted in 53 patients reaching the very severe category. The overall response rate was 46.5%, and complete resolution was achieved in 39.7% of cases. The 100-day overall survival was 34.2%, significantly higher in the patients receiving DF within 2 days of diagnosis (36.0% versus 17.4%; <em>P</em> = .049). High total bilirubin levels at diagnosis and at the worst disease period were strongly associated with poor long-term survival regardless of severity criteria. These data provide real-world support for the early use of DF and suggest the prognostic utility of total bilirubin level in guiding treatment for VOD/SOS following HCT.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 193.e1-193.e11"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293863","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.2025.10.028
Victoria G. Hall , Caden Chiarello , Mats Remberger , Deepali Kumar , Ivan Pasic , Dennis Dong Hwan Kim , Rajat Kumar , Auro Viswabandya , Fotios V. Michelis , Arjun Law , Armin Gerbitz , Sapna Humar , Wilson Lam , Igor Novitzky-Basso , Jonas Mattsson
<div><div>The prevention of herpes zoster (HZ) is of prime importance in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). Shingrix, an inactivated, adjuvanted recombinant zoster vaccine (aRZV), is now available and recommended for preventing HZ in seropositive immunocompromised patients. The safety and efficacy of this vaccine have been established in autologous HCT (autoHCT) recipients and other immunocompromised patients; however, data on alloHCT recipients are limited. The primary outcome of this study was a comparison of HZ frequency in alloHCT recipients who received aRZV vaccination and those who did not. Other characteristics of interest include the clinical presentation of HZ, treatment, and outcomes related to the HZ episode. This single-center retrospective observational cohort study was conducted at Princess Margaret Hospital, Toronto, Canada between April 1, 2018, and May 1, 2024. Adult patients who underwent alloHCT between April 1 2018, and December 31, 2022, were included in a prospective registry. Follow-up was censored at time of death, at 90 days after the first episode of HZ, at loss to follow-up, at the end of the study period, or 36 months post-alloHCT. Data were collected systematically from the electronic medical record or registry. A confirmed HZ episode was defined by clinical and/or molecular criteria. Statistical analysis was performed to determine risk factors associated with HZ and the relative risk (RR) of HZ episodes occurring in those ≥12 months post-alloHCT considering aRZV status and the cumulative follow-up period. A total of 445 patients were included. The median age was 56 years (interquartile range [IQR], 38 to 64 years), with a slight male predominance (n = 241/445; 54.2%). From ≥12 months post-alloHCT, there were 43 HZ episodes, including 26 of 263 patients (9.9%) who had received at least 1 dose of aRZV, 19 of 263 (7.2%) who had received 2 doses, 7 of 70 (10.0%) who did not receive RZV, and 10 of 112 (8.9%) with unknown vaccination status. The median time to HZ after receipt of any dose of aRZV was 8.1 months (IQR, 3.9 to 12.3 months). Overall, the median time to first HZ episode post-alloHCT was 20.7 months (IQR, 16.9 to 27.9 months), and the majority of HZ episodes occurred after cessation of antiviral prophylaxis (n = 38 of 43; 88.4%). Most HZ episodes were localized (n = 38; 88.4%) and treated in the outpatient setting with oral antiviral therapy (n = 39; 90.7%) for a median of 10 days (IQR, 7 to 14 days). Disseminated HZ did not occur in any aRZV recipients. Considering aRZV status and follow-up period, the RR of HZ in those who had received 2 doses of aRZV compared to those who had not received any doses of aRZV was 0.90 (95% confidence interval, 0.75 to 1.07; <em>P</em> = .22). In a sensitivity analysis, the risk of HZ was reduced (lower RR) in those receiving aRZV ≥12 months post-alloHCT compared with those who did not receive aRZV. Overall, the receipt of aRZV did not a
{"title":"Herpes Zoster Frequency and Adjuvanted Recombinant Zoster Vaccination after Allogeneic Hematopoietic Cell Transplantation","authors":"Victoria G. Hall , Caden Chiarello , Mats Remberger , Deepali Kumar , Ivan Pasic , Dennis Dong Hwan Kim , Rajat Kumar , Auro Viswabandya , Fotios V. Michelis , Arjun Law , Armin Gerbitz , Sapna Humar , Wilson Lam , Igor Novitzky-Basso , Jonas Mattsson","doi":"10.1016/j.jtct.2025.10.028","DOIUrl":"10.1016/j.jtct.2025.10.028","url":null,"abstract":"<div><div>The prevention of herpes zoster (HZ) is of prime importance in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). Shingrix, an inactivated, adjuvanted recombinant zoster vaccine (aRZV), is now available and recommended for preventing HZ in seropositive immunocompromised patients. The safety and efficacy of this vaccine have been established in autologous HCT (autoHCT) recipients and other immunocompromised patients; however, data on alloHCT recipients are limited. The primary outcome of this study was a comparison of HZ frequency in alloHCT recipients who received aRZV vaccination and those who did not. Other characteristics of interest include the clinical presentation of HZ, treatment, and outcomes related to the HZ episode. This single-center retrospective observational cohort study was conducted at Princess Margaret Hospital, Toronto, Canada between April 1, 2018, and May 1, 2024. Adult patients who underwent alloHCT between April 1 2018, and December 31, 2022, were included in a prospective registry. Follow-up was censored at time of death, at 90 days after the first episode of HZ, at loss to follow-up, at the end of the study period, or 36 months post-alloHCT. Data were collected systematically from the electronic medical record or registry. A confirmed HZ episode was defined by clinical and/or molecular criteria. Statistical analysis was performed to determine risk factors associated with HZ and the relative risk (RR) of HZ episodes occurring in those ≥12 months post-alloHCT considering aRZV status and the cumulative follow-up period. A total of 445 patients were included. The median age was 56 years (interquartile range [IQR], 38 to 64 years), with a slight male predominance (n = 241/445; 54.2%). From ≥12 months post-alloHCT, there were 43 HZ episodes, including 26 of 263 patients (9.9%) who had received at least 1 dose of aRZV, 19 of 263 (7.2%) who had received 2 doses, 7 of 70 (10.0%) who did not receive RZV, and 10 of 112 (8.9%) with unknown vaccination status. The median time to HZ after receipt of any dose of aRZV was 8.1 months (IQR, 3.9 to 12.3 months). Overall, the median time to first HZ episode post-alloHCT was 20.7 months (IQR, 16.9 to 27.9 months), and the majority of HZ episodes occurred after cessation of antiviral prophylaxis (n = 38 of 43; 88.4%). Most HZ episodes were localized (n = 38; 88.4%) and treated in the outpatient setting with oral antiviral therapy (n = 39; 90.7%) for a median of 10 days (IQR, 7 to 14 days). Disseminated HZ did not occur in any aRZV recipients. Considering aRZV status and follow-up period, the RR of HZ in those who had received 2 doses of aRZV compared to those who had not received any doses of aRZV was 0.90 (95% confidence interval, 0.75 to 1.07; <em>P</em> = .22). In a sensitivity analysis, the risk of HZ was reduced (lower RR) in those receiving aRZV ≥12 months post-alloHCT compared with those who did not receive aRZV. Overall, the receipt of aRZV did not a","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 213.e1-213.e9"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410121","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.2025.10.030
Wilson Y.K. Chan , Pamela P.W. Lee , Daniel K.L. Cheuk , Wing Leung
<div><div>Haploidentical (haplo-) hematopoietic stem cell transplantation (HSCT) has been increasingly used as an alternative transplantation strategy for patients lacking a suitable HLA-matched donor. T cell depletion reduces the risk of graft-versus-host disease (GVHD) but at a cost of increased risk of graft failure, necessitating immediate retransplantation if a cryopreserved autologous graft is not available for rescue. Traditional high-intensity reconditioning with myeloablative and immunoablative regimens of approximately 1 week’s duration aimed at further suppressing the recipient-derived immune system capable of rejecting the primary graft, is associated with high morbidity and mortality. A shortened and reduced-intensity conditioning regimen might reduce infection risk and mortality, but sustained engraftment would be a concern with lowered intensity. Here we report the excellent outcomes of 11 pediatric patients who received a 1-day reduced-intensity preparative regimen prior to retransplantation for graft failure following initial myeloablative haplo-HSCT for various malignant and nonmalignant disease conditions. This was a retrospective study conducted at the Hong Kong Children’s Hospital, the sole territory-wide pediatric HSCT center in Hong Kong. All pediatric patients who were age ≤18 years at the time of initial haplo-HSCT and subsequently underwent salvage haplo-HSCT with a 1-day nonmyeloablative salvage regimen owing to graft failure between June 1, 2021, and May 31, 2024, were included. The salvage regimen consisted of fludarabine (30 mg/m<sup>2</sup>), cyclophosphamide (2000 mg/m<sup>2</sup> or 60 mg/kg), and alemtuzumab (0.3 mg/kg), with or without total body irradiation (2 Gy), all administered 1 day before retransplantation. G-CSF-mobilized peripheral blood stem cells (PBSCs) were collected and transplanted fresh without ex vivo T cell depletion whenever possible, while cryopreserved PBSCs were used if fresh apheresis was not possible. GVHD prophylaxis consisted of cyclosporine, mycophenolate mofetil, tacrolimus, or sirolimus. A total of 11 patients were recruited, including 9 males and 2 females, with a median age of 8.8 years (range, 2.4 to 17.5 years). Underlying diseases included transfusion-dependent anemias (n = 7; beta-thalassemia major = 4, hemoglobin Hammersmith = 1, pyruvate kinase deficiency = 1, severe aplastic anemia = 1), chronic granulomatous disease (n = 1), acute lymphoblastic leukemia (n = 1), post-liver transplant lymphoproliferative disease (n = 1) and neuroblastoma (n = 1). The median interval between haplo-HSCT and administration of the 1-day regimen was 26 days (range, 18 to 50 days). Fresh PBSC grafts were used in 9 patients, and cryopreserved PBSC grafts were used in 2 patients. Median cell viability was 99.6%, with a median stem cell dose of 7.2 × 10<sup>6</sup> CD34<sup>+</sup> cells/kg (range, 4.81 to 20.6 × 10<sup>6</sup> cells/kg) and a median total nucleated cell (TNC) dose of 8.0 × 10<sup>8<
{"title":"Excellent Outcome of 1-Day Nonmyeloablative Salvage Regimen for Pediatric Patients with Graft Failure following Haploidentical Hematopoietic Stem Cell Transplantation","authors":"Wilson Y.K. Chan , Pamela P.W. Lee , Daniel K.L. Cheuk , Wing Leung","doi":"10.1016/j.jtct.2025.10.030","DOIUrl":"10.1016/j.jtct.2025.10.030","url":null,"abstract":"<div><div>Haploidentical (haplo-) hematopoietic stem cell transplantation (HSCT) has been increasingly used as an alternative transplantation strategy for patients lacking a suitable HLA-matched donor. T cell depletion reduces the risk of graft-versus-host disease (GVHD) but at a cost of increased risk of graft failure, necessitating immediate retransplantation if a cryopreserved autologous graft is not available for rescue. Traditional high-intensity reconditioning with myeloablative and immunoablative regimens of approximately 1 week’s duration aimed at further suppressing the recipient-derived immune system capable of rejecting the primary graft, is associated with high morbidity and mortality. A shortened and reduced-intensity conditioning regimen might reduce infection risk and mortality, but sustained engraftment would be a concern with lowered intensity. Here we report the excellent outcomes of 11 pediatric patients who received a 1-day reduced-intensity preparative regimen prior to retransplantation for graft failure following initial myeloablative haplo-HSCT for various malignant and nonmalignant disease conditions. This was a retrospective study conducted at the Hong Kong Children’s Hospital, the sole territory-wide pediatric HSCT center in Hong Kong. All pediatric patients who were age ≤18 years at the time of initial haplo-HSCT and subsequently underwent salvage haplo-HSCT with a 1-day nonmyeloablative salvage regimen owing to graft failure between June 1, 2021, and May 31, 2024, were included. The salvage regimen consisted of fludarabine (30 mg/m<sup>2</sup>), cyclophosphamide (2000 mg/m<sup>2</sup> or 60 mg/kg), and alemtuzumab (0.3 mg/kg), with or without total body irradiation (2 Gy), all administered 1 day before retransplantation. G-CSF-mobilized peripheral blood stem cells (PBSCs) were collected and transplanted fresh without ex vivo T cell depletion whenever possible, while cryopreserved PBSCs were used if fresh apheresis was not possible. GVHD prophylaxis consisted of cyclosporine, mycophenolate mofetil, tacrolimus, or sirolimus. A total of 11 patients were recruited, including 9 males and 2 females, with a median age of 8.8 years (range, 2.4 to 17.5 years). Underlying diseases included transfusion-dependent anemias (n = 7; beta-thalassemia major = 4, hemoglobin Hammersmith = 1, pyruvate kinase deficiency = 1, severe aplastic anemia = 1), chronic granulomatous disease (n = 1), acute lymphoblastic leukemia (n = 1), post-liver transplant lymphoproliferative disease (n = 1) and neuroblastoma (n = 1). The median interval between haplo-HSCT and administration of the 1-day regimen was 26 days (range, 18 to 50 days). Fresh PBSC grafts were used in 9 patients, and cryopreserved PBSC grafts were used in 2 patients. Median cell viability was 99.6%, with a median stem cell dose of 7.2 × 10<sup>6</sup> CD34<sup>+</sup> cells/kg (range, 4.81 to 20.6 × 10<sup>6</sup> cells/kg) and a median total nucleated cell (TNC) dose of 8.0 × 10<sup>8<","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 201.e1-201.e16"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426983","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.2026.01.012
Mithun Vinod Shah
{"title":"Applicability of Allogeneic Hematopoietic Cell Transplant for TP53-Mutated Myeloid Neoplasms: Are We There Yet?","authors":"Mithun Vinod Shah","doi":"10.1016/j.jtct.2026.01.012","DOIUrl":"10.1016/j.jtct.2026.01.012","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 114-117"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081321","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号