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}
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}
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