This retrospective study evaluated the efficacy of desensitization therapy using sirolimus and an anti-CD20 monoclonal antibody (n = 47) plus either plasmapheresis (n = 3) or bortezomib (n = 3) in 53 candidates for haploidentical stem cell transplantation (Haplo-SCT) who had pre-transplant donor-specific anti-HLA antibodies (DSA; mean fluorescence intensity [MFI] ≥ 2000). The patients, with a median age of 46 years (range, 20-70), received desensitization therapy within 40 days before transplantation. The median DSA MFI decreased from 9242 (range, 2156-20,150) before treatment to 3974 (range, 0-16,336) after treatment, 43.4% of the patients became DSA-negative (MFI ≤ 2000), and 62.3% of patients achieved a response, defined as a ≥ 50% reduction in DSA MFI. Among 31 out of 53 patients who underwent transplantation after receiving myeloablative (n = 19) or reduced-intensity conditioning (n = 12) with infusion of haploidentical allografts and umbilical cord blood, all achieved engraftment without primary graft failure or poor graft function. The 100-day cumulative incidence of acute graft-versus-host disease (GVHD) was 25.8% (95% confidence interval [CI], 10.3-41.3%). With a median follow-up of 27 months (range, 3-44), the 1-year cumulative incidence of chronic GVHD was 31.0% (95% CI, 14.1-47.9%). The 1-year cumulative incidences of relapse and non-relapse mortality were 3.2% (95% CI, 0-9.6%) and 10.4% (95% CI, 6.5-14.3%), respectively. The 1-year probabilities of disease-free survival and overall survival were 86.4% and 89.7% (95% CI, 78.5-100%), respectively. These findings suggest that sirolimus combined with an anti-CD20 monoclonal antibody based regimen is an effective desensitization strategy that may improve outcomes in DSA-positive Haplo-SCT recipients.
{"title":"Desensitization therapy using sirolimus and anti-CD20 monoclonal antibody based regimen in haploidentical transplant recipients positive for donor-specific anti-HLA antibodies.","authors":"Ning Ma, Xiang-Yu Zhao, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Xiao-Dong Mo, Yuan-Yuan Zhang, Xiao-Su Zhao, Yi-Fei Cheng, Xiao-Jun Huang, Ying-Jun Chang","doi":"10.1016/j.jtct.2026.01.037","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.01.037","url":null,"abstract":"<p><p>This retrospective study evaluated the efficacy of desensitization therapy using sirolimus and an anti-CD20 monoclonal antibody (n = 47) plus either plasmapheresis (n = 3) or bortezomib (n = 3) in 53 candidates for haploidentical stem cell transplantation (Haplo-SCT) who had pre-transplant donor-specific anti-HLA antibodies (DSA; mean fluorescence intensity [MFI] ≥ 2000). The patients, with a median age of 46 years (range, 20-70), received desensitization therapy within 40 days before transplantation. The median DSA MFI decreased from 9242 (range, 2156-20,150) before treatment to 3974 (range, 0-16,336) after treatment, 43.4% of the patients became DSA-negative (MFI ≤ 2000), and 62.3% of patients achieved a response, defined as a ≥ 50% reduction in DSA MFI. Among 31 out of 53 patients who underwent transplantation after receiving myeloablative (n = 19) or reduced-intensity conditioning (n = 12) with infusion of haploidentical allografts and umbilical cord blood, all achieved engraftment without primary graft failure or poor graft function. The 100-day cumulative incidence of acute graft-versus-host disease (GVHD) was 25.8% (95% confidence interval [CI], 10.3-41.3%). With a median follow-up of 27 months (range, 3-44), the 1-year cumulative incidence of chronic GVHD was 31.0% (95% CI, 14.1-47.9%). The 1-year cumulative incidences of relapse and non-relapse mortality were 3.2% (95% CI, 0-9.6%) and 10.4% (95% CI, 6.5-14.3%), respectively. The 1-year probabilities of disease-free survival and overall survival were 86.4% and 89.7% (95% CI, 78.5-100%), respectively. These findings suggest that sirolimus combined with an anti-CD20 monoclonal antibody based regimen is an effective desensitization strategy that may improve outcomes in DSA-positive Haplo-SCT recipients.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158368","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 : 2026-02-07DOI: 10.1016/j.jtct.2026.02.001
Pashna N Munshi, Carrie Yuen, Taha Al-Juhaishi, Erica Jensen, Eneida R Nemecek, Brenda Sandmaier, Stella M Davies, Jeffery J Auletta, Jennifer Holter Chakrabarty
Autologous stem cell transplant (ASCT) and chimeric antigen receptor T cell therapy (CAR T) are approved treatments both with curative potential and/or excellent response rates in patients with aggressive hematologic malignancies. However, multiple barriers hinder the delivery of these treatments and thereby affecting access to patients. Minority patients are less likely to receive ASCT, and when they do, outcomes may not match those of non-minority patients, highlighting the need for accountability and targeted interventions to prevent further widening of disparities. Patient, physician, product, and logistics-related barriers further make life-saving treatments inequitable. Medicaid and public insurance coverage gaps, as well as social determinants of health, continue to limit access and worsen outcomes for ethnically diverse populations. Additionally, delays and lack of referral from physicians to cellular therapy specialists add to the problem with a risk of relapsed and missed opportunity for these treatments. Addressing these barriers with a sense of urgency especially in the era of expanding cell therapy indications could save many patients from succumbing to disease. The American Society of Transplantation and Cellular Therapy (ASTCT) and NMDP (formerly known as the National Marrow Donor Program) collaborate to investigate and address these barriers at a national level. This paper highlights treatment barriers and potential strategies to reduce them at individual program and ecosystem levels.
{"title":"Breaking Access Barriers to Autologous Stem Cell Transplant and Chimeric Antigen Receptor T Cell therapy in Hematological Malignancies - an ASTCT-NMDP ACCESS Initiative.","authors":"Pashna N Munshi, Carrie Yuen, Taha Al-Juhaishi, Erica Jensen, Eneida R Nemecek, Brenda Sandmaier, Stella M Davies, Jeffery J Auletta, Jennifer Holter Chakrabarty","doi":"10.1016/j.jtct.2026.02.001","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.02.001","url":null,"abstract":"<p><p>Autologous stem cell transplant (ASCT) and chimeric antigen receptor T cell therapy (CAR T) are approved treatments both with curative potential and/or excellent response rates in patients with aggressive hematologic malignancies. However, multiple barriers hinder the delivery of these treatments and thereby affecting access to patients. Minority patients are less likely to receive ASCT, and when they do, outcomes may not match those of non-minority patients, highlighting the need for accountability and targeted interventions to prevent further widening of disparities. Patient, physician, product, and logistics-related barriers further make life-saving treatments inequitable. Medicaid and public insurance coverage gaps, as well as social determinants of health, continue to limit access and worsen outcomes for ethnically diverse populations. Additionally, delays and lack of referral from physicians to cellular therapy specialists add to the problem with a risk of relapsed and missed opportunity for these treatments. Addressing these barriers with a sense of urgency especially in the era of expanding cell therapy indications could save many patients from succumbing to disease. The American Society of Transplantation and Cellular Therapy (ASTCT) and NMDP (formerly known as the National Marrow Donor Program) collaborate to investigate and address these barriers at a national level. This paper highlights treatment barriers and potential strategies to reduce them at individual program and ecosystem levels.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150605","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 : 2026-02-05DOI: 10.1016/j.jtct.2026.02.002
Daichi Kishi, Yoshimitsu Shimomura, Daisuke Yamashita, Masashi Nishikubo, Ami Masaoka, Azusa Uchimoto, Tadakazu Kondo
Background: Liver dysfunction is a frequent complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It may occur in both the early and late post-transplantation phases, with distinct etiologies. Chronic graft-versus-host disease is a well-known cause of late-onset liver dysfunction; however, other etiologies should also be considered. Among them, autoimmune-like hepatitis (AILH) is a rare but clinically significant complication.
Objectives: We aimed to analyze patients who developed AILH after allo-HSCT to determine its incidence, clinical features, histological findings, and responses to treatment.
Study design: We retrospectively reviewed 228 consecutive patients who underwent their first allo-HSCT without treatment failure by day 100 after allo-HSCT at our institution between April 2013 and December 2024. The cumulative incidence of liver injury after allo-HSCT was calculated using a competing risk model that included death, relapse, and a second transplantation due to graft failure as competing events.
Results: Among the study patients, 75 developed liver injury. A liver biopsy was performed in 13 patients, and eight met the pathological criteria for AILH. In patients diagnosed with AILH, the median age at allo-HSCT was 57 years, and the median onset of AILH was 300 days after allo-HSCT. Prednisolone (PSL) was administered to six of eight patients. All patients, including those who did not receive PSL, achieved a response, defined as an improvement in all liver enzymes, at a median of 28.5 days.
Conclusions: AILH is a rare but distinct form of liver injury that tends to occur in the late post-transplantation phase and shows an excellent response to corticosteroids.
{"title":"Clinical characteristics and treatment outcomes of autoimmune-like hepatitis after allogeneic hematopoietic stem cell transplantation.","authors":"Daichi Kishi, Yoshimitsu Shimomura, Daisuke Yamashita, Masashi Nishikubo, Ami Masaoka, Azusa Uchimoto, Tadakazu Kondo","doi":"10.1016/j.jtct.2026.02.002","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.02.002","url":null,"abstract":"<p><strong>Background: </strong>Liver dysfunction is a frequent complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). It may occur in both the early and late post-transplantation phases, with distinct etiologies. Chronic graft-versus-host disease is a well-known cause of late-onset liver dysfunction; however, other etiologies should also be considered. Among them, autoimmune-like hepatitis (AILH) is a rare but clinically significant complication.</p><p><strong>Objectives: </strong>We aimed to analyze patients who developed AILH after allo-HSCT to determine its incidence, clinical features, histological findings, and responses to treatment.</p><p><strong>Study design: </strong>We retrospectively reviewed 228 consecutive patients who underwent their first allo-HSCT without treatment failure by day 100 after allo-HSCT at our institution between April 2013 and December 2024. The cumulative incidence of liver injury after allo-HSCT was calculated using a competing risk model that included death, relapse, and a second transplantation due to graft failure as competing events.</p><p><strong>Results: </strong>Among the study patients, 75 developed liver injury. A liver biopsy was performed in 13 patients, and eight met the pathological criteria for AILH. In patients diagnosed with AILH, the median age at allo-HSCT was 57 years, and the median onset of AILH was 300 days after allo-HSCT. Prednisolone (PSL) was administered to six of eight patients. All patients, including those who did not receive PSL, achieved a response, defined as an improvement in all liver enzymes, at a median of 28.5 days.</p><p><strong>Conclusions: </strong>AILH is a rare but distinct form of liver injury that tends to occur in the late post-transplantation phase and shows an excellent response to corticosteroids.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137851","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 : 2026-02-04DOI: 10.1016/j.jtct.2026.01.032
Guillermo J Ruiz-Argüelles, Juan Carlos Olivares-Gazca, Sergio Giralt, José Emiliano Montelongo-Cepeda, David Gómez-Almaguer
{"title":"Innovations in Hematopoietic Stem Cell Transplants in Low and Middle-Income Countries: A Mexican Perspective.","authors":"Guillermo J Ruiz-Argüelles, Juan Carlos Olivares-Gazca, Sergio Giralt, José Emiliano Montelongo-Cepeda, David Gómez-Almaguer","doi":"10.1016/j.jtct.2026.01.032","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.01.032","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132952","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 : 2026-02-02DOI: 10.1016/j.jtct.2026.01.031
A A Hawkes, S G Kasimsetty, H Li, G P Morris, S M Kurian, S Almeida, S E DeWolf, D B McKay
<p><strong>Background: </strong>Hematopoietic stem cell transplantation (HSCT) remains limited by inefficient donor cell engraftment, which is influenced by inflammatory stress responses triggered during conditioning and immune reconstitution. While immune-mediated barriers have been extensively studied, the molecular regulators within donor hematopoietic stem and progenitor cells (HSPCs) that influence engraftment efficiency remain less defined. NOD1 and NOD2 are cytosolic pattern recognition receptors (PRRs) traditionally known for sensing bacterial peptidoglycans and initiating innate immune signaling. However, emerging data suggest that NOD1/2 signaling may be directly activated by cellular stressors that intersect with cellular stress pathways critical to HSPC function. Our previous work has demonstrated that NOD1 and NOD2 play a critical role in modulating sterile inflammation, a key component of the transplant environment. This positions these PRRs as potential regulators of HSPC stress responses and survival during transplantation. Despite this, the cell-intrinsic role of NOD1 and NOD2 in donor HSPC engraftment has not been fully explored. Understanding how these innate immune sensors influence HSPC function in the absence of infection could reveal novel strategies to improve engraftment and long-term chimerism following HSCT.</p><p><strong>Objective: </strong>This study aims to determine whether the cytosolic pattern recognition receptors NOD1 and NOD2 intrinsically regulate hematopoietic stem cell reconstitution and to define the underlying mechanisms by which their deletion may enhance donor cell persistence and chimerism in transplant settings.</p><p><strong>Study design: </strong>We evaluated NOD1/2 expression in murine HSPCs, tested reconstitution efficiency of wild-type (WT) versus NOD1/2 double knockout (NOD1×2<sup>⁻/⁻</sup>) donor cells in syngeneic and allogeneic recipients, and performed competitive transplant assays to assess cell-intrinsic effects. In addition, we tested the effect of NOD1/2 deletion in HSPCs on long-term survival, allograft rejection and tumor immunosurveillance. Transcriptomic profiling was performed to define mechanisms underlying altered reconstitution.</p><p><strong>Results: </strong>HSPCs constitutively expressed NOD1 and NOD2, and their transcription was upregulated by endotoxin and NOD ligands. Genetic deletion of NOD1/2 significantly increased donor cell reconstitution and long-term chimerism in both syngeneic and fully allogeneic recipients, with NOD1×2<sup>⁻/⁻</sup> cells outcompeting WT cells in competitive transplantation. Enhanced chimerism was observed across bone marrow, blood, spleen, and lymph nodes, without altering immune lineage differentiation. NOD1×2<sup>⁻/⁻</sup> chimeras showed normal survival, intact alloresponsiveness, and preserved tumor immunosurveillance. Transcriptomic profiling revealed significant reprogramming of NOD1×2<sup>⁻/⁻</sup> donor HSPCs, with highly significant alter
{"title":"Simultaneous NOD1 and NOD2 Deletion in Hematopoietic Stem and Progenitor cells Promotes Long-Term Donor Chimerism.","authors":"A A Hawkes, S G Kasimsetty, H Li, G P Morris, S M Kurian, S Almeida, S E DeWolf, D B McKay","doi":"10.1016/j.jtct.2026.01.031","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.01.031","url":null,"abstract":"<p><strong>Background: </strong>Hematopoietic stem cell transplantation (HSCT) remains limited by inefficient donor cell engraftment, which is influenced by inflammatory stress responses triggered during conditioning and immune reconstitution. While immune-mediated barriers have been extensively studied, the molecular regulators within donor hematopoietic stem and progenitor cells (HSPCs) that influence engraftment efficiency remain less defined. NOD1 and NOD2 are cytosolic pattern recognition receptors (PRRs) traditionally known for sensing bacterial peptidoglycans and initiating innate immune signaling. However, emerging data suggest that NOD1/2 signaling may be directly activated by cellular stressors that intersect with cellular stress pathways critical to HSPC function. Our previous work has demonstrated that NOD1 and NOD2 play a critical role in modulating sterile inflammation, a key component of the transplant environment. This positions these PRRs as potential regulators of HSPC stress responses and survival during transplantation. Despite this, the cell-intrinsic role of NOD1 and NOD2 in donor HSPC engraftment has not been fully explored. Understanding how these innate immune sensors influence HSPC function in the absence of infection could reveal novel strategies to improve engraftment and long-term chimerism following HSCT.</p><p><strong>Objective: </strong>This study aims to determine whether the cytosolic pattern recognition receptors NOD1 and NOD2 intrinsically regulate hematopoietic stem cell reconstitution and to define the underlying mechanisms by which their deletion may enhance donor cell persistence and chimerism in transplant settings.</p><p><strong>Study design: </strong>We evaluated NOD1/2 expression in murine HSPCs, tested reconstitution efficiency of wild-type (WT) versus NOD1/2 double knockout (NOD1×2<sup>⁻/⁻</sup>) donor cells in syngeneic and allogeneic recipients, and performed competitive transplant assays to assess cell-intrinsic effects. In addition, we tested the effect of NOD1/2 deletion in HSPCs on long-term survival, allograft rejection and tumor immunosurveillance. Transcriptomic profiling was performed to define mechanisms underlying altered reconstitution.</p><p><strong>Results: </strong>HSPCs constitutively expressed NOD1 and NOD2, and their transcription was upregulated by endotoxin and NOD ligands. Genetic deletion of NOD1/2 significantly increased donor cell reconstitution and long-term chimerism in both syngeneic and fully allogeneic recipients, with NOD1×2<sup>⁻/⁻</sup> cells outcompeting WT cells in competitive transplantation. Enhanced chimerism was observed across bone marrow, blood, spleen, and lymph nodes, without altering immune lineage differentiation. NOD1×2<sup>⁻/⁻</sup> chimeras showed normal survival, intact alloresponsiveness, and preserved tumor immunosurveillance. Transcriptomic profiling revealed significant reprogramming of NOD1×2<sup>⁻/⁻</sup> donor HSPCs, with highly significant alter","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146120291","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.2025.10.006
Brittany Salter , Adam Suleman , Robert Kridel , Amy M. Trottier , Regina Li , Matthew Binnie , Amaris K. Balitsky , Gwynivere A. Davies
Post-transplant lymphoproliferative disorder (PTLD) is a rare malignancy following solid organ transplantation (SOT), with lung transplant recipients experiencing disproportionately high rates of progression and mortality. While CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated efficacy in relapsed/refractory (R/R) B-cell lymphoma, its role in PTLD remains underexplored, particularly in lung SOT.
We present a multi-center retrospective study of three lung transplant recipients treated with Axicabtagene ciloleucel (Axicel) for R/R PTLD. All patients had received multiple lines of prior therapy, including chemoimmunotherapy, with one patient also receiving EBV-specific T-cell therapy (Tabelecleucel). CAR-T therapy resulted in complete or partial response in all three patients, although one subsequently developed allograft rejection. Immunosuppression (IST) was held at the time of lymphodepletion and re-introduced variably post-CAR-T depending on risk of rejection versus risk of relapse/recurrence. Cytokine release syndrome (CRS) was observed in all cases but was mild, occurred early post-CAR-T, and managed effectively with tocilizumab with/without dexamethasone
Our study highlights the feasibility of CAR-T therapy in lung SOT recipients with PTLD, with promising responses and manageable toxicities. Individualized and judicious modification of IST around CAR-T infusion is critical to balance efficacy and disease relapse with lung allograft preservation. These cases highlight the limitations of current CAR-T studies, which have excluded this high-risk, immunologically complex patient population, and underscore the need for further publications in this patient subset to better understand how to manage IST around CAR-T.
{"title":"CAR-T for Management of R/R PTLD Following Lung Transplant: A Multi-center Retrospective Study","authors":"Brittany Salter , Adam Suleman , Robert Kridel , Amy M. Trottier , Regina Li , Matthew Binnie , Amaris K. Balitsky , Gwynivere A. Davies","doi":"10.1016/j.jtct.2025.10.006","DOIUrl":"10.1016/j.jtct.2025.10.006","url":null,"abstract":"<div><div>Post-transplant lymphoproliferative disorder (PTLD) is a rare malignancy following solid organ transplantation (SOT), with lung transplant recipients experiencing disproportionately high rates of progression and mortality. While CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated efficacy in relapsed/refractory (R/R) B-cell lymphoma, its role in PTLD remains underexplored, particularly in lung SOT.</div><div>We present a multi-center retrospective study of three lung transplant recipients treated with Axicabtagene ciloleucel (Axicel) for R/R PTLD. All patients had received multiple lines of prior therapy, including chemoimmunotherapy, with one patient also receiving EBV-specific T-cell therapy (Tabelecleucel). CAR-T therapy resulted in complete or partial response in all three patients, although one subsequently developed allograft rejection. Immunosuppression (IST) was held at the time of lymphodepletion and re-introduced variably post-CAR-T depending on risk of rejection versus risk of relapse/recurrence. Cytokine release syndrome (CRS) was observed in all cases but was mild, occurred early post-CAR-T, and managed effectively with tocilizumab with/without dexamethasone</div><div>Our study highlights the feasibility of CAR-T therapy in lung SOT recipients with PTLD, with promising responses and manageable toxicities. Individualized and judicious modification of IST around CAR-T infusion is critical to balance efficacy and disease relapse with lung allograft preservation. These cases highlight the limitations of current CAR-T studies, which have excluded this high-risk, immunologically complex patient population, and underscore the need for further publications in this patient subset to better understand how to manage IST around CAR-T.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 119.e1-119.e6"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276067","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.2025.12.108
Alycia Hatashima PharmD , Xinyi Fan MS , Jeanne McCarthy-Kaiser PharmD , Amanda Peffer PharmD , Chris Davis MS , Ryan Basom BS , Bee Chua PharmD , Natalie Wuliji DO , Masumi Ueda Oshima MD, MA , Prof. Brenda M. Sandmaier MD , Timothy W Randolph PhD , Marco Mielcarek MD, PhD , Naveed J. Ali MD
<div><h3>Introduction</h3><div>Cyclophosphamide (Cy) plus high dose total body irradiation or busulfan are standard myeloablative conditioning (MAC) regimens for allogeneic hematopoietic cell transplant (alloHCT). Cy causes dose-dependent toxicities resulting in significant morbidity and mortality, particularly in obese patients. There is conflicting data regarding the impact of weight-based Cy dosing on clinical outcomes in obese individuals.</div></div><div><h3>Methods</h3><div>In this retrospective study, patients (≥18 years) who received high dose Cy (≥100 mg/kg)-based pre-transplant conditioning between 1/2010 and 3/2025 at Fred Hutchinson Cancer Center were included. Cy was dosed using actual weight or 25% adjusted body weight if actual weight exceeded 100% of ideal body weight. Patients were stratified by body mass index (BMI): <25 mg/m<sup>2</sup> (normal weight), 25-29.9 mg/m<sup>2</sup> (overweight), and ≥30 mg/m<sup>2</sup> (obese). Non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) probabilities with 95% confidence intervals were estimated using cumulative incidence, considering appropriate competing risks. Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Linear Cox regression modeling was applied to assess associations between BMI and clinical outcomes.</div></div><div><h3>Results</h3><div>Eligible for analysis were 880 patients (Table 1). Conditioning intensity was predominantly MAC (>95%), and GVHD prophylaxis did not include post-transplant Cy (PTCy). The NRM significantly differed between normal weight (low), overweight (intermediate) and obese (high) patients at day 100 (2% [1-5] vs 3% [2-6] vs 6% [3-9]), day 180 (4% [3-7] vs 7% [5-11] vs 10% [7-14]) and 1 year (7% [4-10] vs 12% [8-16] vs 17% [13-21]; Figure 1a). While the incidences of grade II-IV aGVHD were similar in the three groups, grade III-IV aGVHD was significantly higher in obese relative to overweight and normal weight patients (21% [17-26] vs 15% [11-20] vs 13% [10-18]; Figure 1b). The 1-year cumulative incidence of moderate-severe cGVHD requiring systemic therapy was only numerically higher in obese compared to overweight and normal weight patients (31% vs 25% vs 26%; Figure 1c). In multivariable analysis, BMI remained significantly associated with higher NRM (HR 1.03 [95% CI, 1-1.05], p=0.02) and trended towards higher grade III-IV aGVHD (HR 1.02 [95% CI, 1-1.05], p=0.06). A significant association was not observed between BMI and DFS and OS (Figure 1d).</div></div><div><h3>Conclusion</h3><div>We demonstrate that high dose Cy-based MAC is associated with a higher risk of NRM in overweight and obese patients, primarily driven by higher rates of severe aGVHD in the context of non-PTCy-based GVHD prophylaxis. Strategies to reduce GVHD (such as employing PTCy) may lower NRM risk in obese patients. Further, pharmacokinetic analysis could provide guidance to optimize Cy dosing
环磷酰胺（Cy）加高剂量全身照射或丁硫丹是同种异体造血细胞移植（allogenetic hematopoietic cell transplant, alloHCT）的标准清髓调节（myeleloative conditioning， MAC）方案。Cy引起剂量依赖性毒性，导致显著发病率和死亡率，特别是在肥胖患者中。关于基于体重的Cy剂量对肥胖个体临床结果的影响，有相互矛盾的数据。方法本回顾性研究纳入2010年1月至2025年3月期间在Fred Hutchinson癌症中心接受高剂量Cy（≥100mg /kg）移植前调理的患者（≥18岁）。Cy以实际体重给药，如果实际体重超过理想体重的100%，则以调整体重的25%给药。根据体重指数（BMI）对患者进行分层：25 mg/m2（正常体重），25-29.9 mg/m2（超重），≥30 mg/m2（肥胖）。非复发死亡率（NRM）、急性移植物抗宿主病（aGVHD）和慢性移植物抗宿主病（cGVHD）概率在95%置信区间内使用累积发病率进行估计，并考虑适当的竞争风险。Kaplan-Meier法估计总生存期（OS）和无病生存期（DFS）。采用线性Cox回归模型评估BMI与临床结果之间的关系。结果符合分析条件的患者有880例（表1）。调节强度主要是MAC (>95%)， GVHD预防不包括移植后Cy （PTCy）。正常体重（低）、超重（中等）和肥胖（高）患者的NRM在第100天（2% [1-5]vs 3% [2-6] vs 6%[3-9]）、第180天（4% [3-7]vs 7% [5-11] vs 10%[7-14]）和第1年（7% [4-10]vs 12% [8-16] vs 17%[13-21]；图1a）差异显著。虽然三组II-IV级aGVHD的发生率相似，但肥胖患者的III-IV级aGVHD明显高于超重和正常体重患者（21% [17-26]vs 15% [11-20] vs 13%[10-18]；图1b）。与超重和正常体重患者相比，肥胖患者需要全身治疗的中重度cGVHD的1年累积发病率仅在数字上较高（31% vs 25% vs 26%；图1c）。在多变量分析中，BMI与较高的NRM （HR 1.03 [95% CI, 1-1.05], p=0.02）和较高的III-IV级aGVHD （HR 1.02 [95% CI, 1-1.05], p=0.06）保持显著相关。BMI与DFS和OS之间没有明显的关联（图1d）。结论：我们证明，在超重和肥胖患者中，高剂量基于ptc的MAC与更高的NRM风险相关，主要是由于在非基于ptc的GVHD预防背景下，严重aGVHD的发生率更高。降低GVHD的策略（如使用PTCy）可能降低肥胖患者的NRM风险。此外，药代动力学分析可为肥胖患者优化Cy剂量提供指导。
{"title":"Higher Incidence of Severe Acute GVHD and NRM Following High Dose Cyclophosphamide Based Conditioning Regimen in Overweight and Obese Patients Undergoing Allogeneic HCT","authors":"Alycia Hatashima PharmD , Xinyi Fan MS , Jeanne McCarthy-Kaiser PharmD , Amanda Peffer PharmD , Chris Davis MS , Ryan Basom BS , Bee Chua PharmD , Natalie Wuliji DO , Masumi Ueda Oshima MD, MA , Prof. Brenda M. Sandmaier MD , Timothy W Randolph PhD , Marco Mielcarek MD, PhD , Naveed J. Ali MD","doi":"10.1016/j.jtct.2025.12.108","DOIUrl":"10.1016/j.jtct.2025.12.108","url":null,"abstract":"<div><h3>Introduction</h3><div>Cyclophosphamide (Cy) plus high dose total body irradiation or busulfan are standard myeloablative conditioning (MAC) regimens for allogeneic hematopoietic cell transplant (alloHCT). Cy causes dose-dependent toxicities resulting in significant morbidity and mortality, particularly in obese patients. There is conflicting data regarding the impact of weight-based Cy dosing on clinical outcomes in obese individuals.</div></div><div><h3>Methods</h3><div>In this retrospective study, patients (≥18 years) who received high dose Cy (≥100 mg/kg)-based pre-transplant conditioning between 1/2010 and 3/2025 at Fred Hutchinson Cancer Center were included. Cy was dosed using actual weight or 25% adjusted body weight if actual weight exceeded 100% of ideal body weight. Patients were stratified by body mass index (BMI): <25 mg/m<sup>2</sup> (normal weight), 25-29.9 mg/m<sup>2</sup> (overweight), and ≥30 mg/m<sup>2</sup> (obese). Non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) probabilities with 95% confidence intervals were estimated using cumulative incidence, considering appropriate competing risks. Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival (DFS). Linear Cox regression modeling was applied to assess associations between BMI and clinical outcomes.</div></div><div><h3>Results</h3><div>Eligible for analysis were 880 patients (Table 1). Conditioning intensity was predominantly MAC (>95%), and GVHD prophylaxis did not include post-transplant Cy (PTCy). The NRM significantly differed between normal weight (low), overweight (intermediate) and obese (high) patients at day 100 (2% [1-5] vs 3% [2-6] vs 6% [3-9]), day 180 (4% [3-7] vs 7% [5-11] vs 10% [7-14]) and 1 year (7% [4-10] vs 12% [8-16] vs 17% [13-21]; Figure 1a). While the incidences of grade II-IV aGVHD were similar in the three groups, grade III-IV aGVHD was significantly higher in obese relative to overweight and normal weight patients (21% [17-26] vs 15% [11-20] vs 13% [10-18]; Figure 1b). The 1-year cumulative incidence of moderate-severe cGVHD requiring systemic therapy was only numerically higher in obese compared to overweight and normal weight patients (31% vs 25% vs 26%; Figure 1c). In multivariable analysis, BMI remained significantly associated with higher NRM (HR 1.03 [95% CI, 1-1.05], p=0.02) and trended towards higher grade III-IV aGVHD (HR 1.02 [95% CI, 1-1.05], p=0.06). A significant association was not observed between BMI and DFS and OS (Figure 1d).</div></div><div><h3>Conclusion</h3><div>We demonstrate that high dose Cy-based MAC is associated with a higher risk of NRM in overweight and obese patients, primarily driven by higher rates of severe aGVHD in the context of non-PTCy-based GVHD prophylaxis. Strategies to reduce GVHD (such as employing PTCy) may lower NRM risk in obese patients. Further, pharmacokinetic analysis could provide guidance to optimize Cy dosing","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S72-S73"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098475","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.2025.12.049
Zachary Braunstein MD , Eric McLaughlin MS , Prasanth Lingamaneni MBBS , Stefan K. Barta MD, MS , Miao Cao BS , Tiffany Chang MS , Nivetha Ganesan MPH , Tanaya Shree MD, PhD , Binh Luu MS , Neha Mehta-Shah MD, MSCI , Marcus Watkins PhD , Jasmine Zain MD , Pamela Allen MD, MSc , Darina Paulino MS , Brittany Adams BS , Jie Wang MD , Amber Feng MD , Enrica Marchi MD, PhD , Nathan Roberts MD , Ryan Wilcox MD, PhD , Jonathan E. Brammer MD
Introduction
T-PLL is a rare, aggressive leukemia with poor prognosis and limited therapies. Previous studies on T-PLL patients receiving an alloSCT are limited by small numbers with limited disease and transplant characteristics. Our recent data demonstrated significant survival difference between TCL1A+/- T-PLL, and CD8+/- T-PLL.
Methods
We retrospectively evaluated 572 diagnosed with T-PLL at 21 academic cancer centers, of which 169 proceeded with alloSCT. Survival characteristics were assessed using Kaplan-Meier methods and Cox proportional hazard models.
Results
Among 169 alloSCT recipients with T-PLL, median follow-up time was 20.9 months post-alloSCT, the median age at transplant was 59 years (range: 35-77) and 52% were male, and 69% were TCL1A+. 90 (53%) of patients were CD4+CD8-, 17 (10%) were CD4-CD8+ and 52, (31%) were CD4+CD8+. At alloSCT, 136 (80%) patients were in CR and 23 (14%) patients were in PR. 45% (43/96) of known patients had minimal residual disease (MRD) at the time of alloSCT. 49 (30%) had myeloablative conditioning (MAC) and 114 (70%) had reduced intensity conditioning (RIC). 80 (49%) patients had total body irradiation (TBI) within conditioning. The most common regimens were fludarabine (Flu)/melphalan based regimens (n=44; 26.0%), lu/cyclophosphamide (Cy) based regimens (n=33; 19.5%), Flu/Busulfan based regimens (n=22; 13.0%), and Flu/TBI (n=8; 4.7%).
The median OS (Figure 1) and PFS post-alloSCT was 32.6 months (95% CI: 21.0-41.9) and 20.8 months (95% CI: 14.4-30.5) months while the 1-year cumulative incidences (CI) of NRM and relapse were 17% and 20%. The incidences of grade II-IV acute and chronic GVHD were 19% and 23%. There was no difference between MAC or RIC in OS or PFS (Table 1). Patients that were MRD+ had worse OS and PFS and higher rates of relapse (1-year relapse 20% vs 8%; p=0.08) (Table 1). PFS was improved in those who received alloSCT though only trended towards significance due to low numbers (HR 0.76, p=0.09).
TCL1A+ disease had significantly worse OS (21.6 vs 63.1; p=0.01) and PFS (12.4 vs 50.7; p=0.01) (Table 2). Additionally, CI of NRM (24% vs 3%; p=0.02) and relapse (25% vs 12%; p=0.86) was higher in TCL1A+ PLL. CD4+CD8-, CD4-CD8+, and CD4+CD8+ disease had no difference in survival via either OS or PFS (Table 2) as well as no difference 1-year CI of NRM (11.6 vs 23.5 vs 26.2; p=0.35) and relapse (18.5 vs 23.5 vs 20.0; p=0.67).
Conclusions
AlloSCT significantly improved outcomes for patients with T-PLL and remains the only curative therapy. OS, PFS, and CI relapse were significantly worse for patients with TCL1A+ T-PLL, MRD positivity, or PR prior to alloSCT. Novel strategies to decrease relapse such as post-alloSCT maintenance therapy to improve outcomes are urgently needed in these patients.
t - pll是一种罕见的侵袭性白血病，预后差，治疗方法有限。先前关于接受同种异体细胞移植的T-PLL患者的研究数量有限，疾病和移植特征有限。我们最近的数据显示TCL1A+/- T-PLL和CD8+/- T-PLL之间存在显著的生存差异。方法回顾性评价21个学术癌症中心572例诊断为T-PLL的患者，其中169例进行了同种异体细胞移植。采用Kaplan-Meier法和Cox比例风险模型评估生存特征。结果169例同种异体细胞移植T-PLL受者中位随访时间为20.9个月，移植时中位年龄为59岁（范围：35-77岁），52%为男性，69%为TCL1A+。CD4+CD8- 90例（53%），CD4-CD8+ 17例（10%），CD4+CD8+ 52例（31%）。在同种异体细胞移植时，136例（80%）患者处于CR， 23例（14%）患者处于PR。45%（43/96）的已知患者在同种异体细胞移植时存在微小残留疾病（MRD）。49例（30%）有清髓调节（MAC）， 114例（70%）有降低强度调节（RIC）。80例（49%）患者接受全身照射（TBI）。最常见的方案是氟达拉滨(Flu)/美法兰为基础的方案（n=44; 26.0%）， lu/环磷酰胺（Cy）为基础的方案（n=33; 19.5%）， Flu/Busulfan为基础的方案（n=22; 13.0%）和Flu/TBI （n=8; 4.7%）。移植后的中位OS（图1）和PFS分别为32.6个月（95% CI: 21.0-41.9）和20.8个月（95% CI: 14.4-30.5）个月，NRM和复发的1年累积发生率（CI）分别为17%和20%。II-IV级急性和慢性GVHD的发生率分别为19%和23%。MAC和RIC在OS和PFS方面没有差异（表1）。MRD+患者的OS和PFS更差，复发率更高（1年复发率20% vs 8%； p=0.08）（表1）。接受同种异体细胞移植的患者的PFS得到改善，但由于数量较少，PFS趋向显著（HR 0.76, p=0.09）。TCL1A+疾病的OS （21.6 vs 63.1, p=0.01）和PFS （12.4 vs 50.7, p=0.01）明显较差（表2）。此外，TCL1A+ PLL的NRM CI （24% vs 3%, p=0.02）和复发CI （25% vs 12%, p=0.86）更高。CD4+CD8-、CD4-CD8+和CD4+CD8+疾病通过OS或PFS的生存无差异（表2），NRM的1年CI （11.6 vs 23.5 vs 26.2, p=0.35）和复发（18.5 vs 23.5 vs 20.0, p=0.67）无差异。结论sct可显著改善T-PLL患者的预后，仍然是唯一的治疗方法。移植前TCL1A+ T-PLL、MRD阳性或PR患者的OS、PFS和CI复发明显更差。这些患者迫切需要新的策略来减少复发，如异体细胞移植后维持治疗以改善预后。
{"title":"Allogeneic Stem Cell Transplant Results in T-cell Prolymphocytic Leukemia (T-PLL): A Collaborative Multi-Center Study Cohort","authors":"Zachary Braunstein MD , Eric McLaughlin MS , Prasanth Lingamaneni MBBS , Stefan K. Barta MD, MS , Miao Cao BS , Tiffany Chang MS , Nivetha Ganesan MPH , Tanaya Shree MD, PhD , Binh Luu MS , Neha Mehta-Shah MD, MSCI , Marcus Watkins PhD , Jasmine Zain MD , Pamela Allen MD, MSc , Darina Paulino MS , Brittany Adams BS , Jie Wang MD , Amber Feng MD , Enrica Marchi MD, PhD , Nathan Roberts MD , Ryan Wilcox MD, PhD , Jonathan E. Brammer MD","doi":"10.1016/j.jtct.2025.12.049","DOIUrl":"10.1016/j.jtct.2025.12.049","url":null,"abstract":"<div><h3>Introduction</h3><div>T-PLL is a rare, aggressive leukemia with poor prognosis and limited therapies. Previous studies on T-PLL patients receiving an alloSCT are limited by small numbers with limited disease and transplant characteristics. Our recent data demonstrated significant survival difference between TCL1A+/- T-PLL, and CD8+/- T-PLL.</div></div><div><h3>Methods</h3><div>We retrospectively evaluated 572 diagnosed with T-PLL at 21 academic cancer centers, of which 169 proceeded with alloSCT. Survival characteristics were assessed using Kaplan-Meier methods and Cox proportional hazard models.</div></div><div><h3>Results</h3><div>Among 169 alloSCT recipients with T-PLL, median follow-up time was 20.9 months post-alloSCT, the median age at transplant was 59 years (range: 35-77) and 52% were male, and 69% were TCL1A+. 90 (53%) of patients were CD4+CD8-, 17 (10%) were CD4-CD8+ and 52, (31%) were CD4+CD8+. At alloSCT, 136 (80%) patients were in CR and 23 (14%) patients were in PR. 45% (43/96) of known patients had minimal residual disease (MRD) at the time of alloSCT. 49 (30%) had myeloablative conditioning (MAC) and 114 (70%) had reduced intensity conditioning (RIC). 80 (49%) patients had total body irradiation (TBI) within conditioning. The most common regimens were fludarabine (Flu)/melphalan based regimens (n=44; 26.0%), lu/cyclophosphamide (Cy) based regimens (n=33; 19.5%), Flu/Busulfan based regimens (n=22; 13.0%), and Flu/TBI (n=8; 4.7%).</div><div>The median OS (Figure 1) and PFS post-alloSCT was 32.6 months (95% CI: 21.0-41.9) and 20.8 months (95% CI: 14.4-30.5) months while the 1-year cumulative incidences (CI) of NRM and relapse were 17% and 20%. The incidences of grade II-IV acute and chronic GVHD were 19% and 23%. There was no difference between MAC or RIC in OS or PFS (Table 1). Patients that were MRD+ had worse OS and PFS and higher rates of relapse (1-year relapse 20% vs 8%; p=0.08) (Table 1). PFS was improved in those who received alloSCT though only trended towards significance due to low numbers (HR 0.76, p=0.09).</div><div>TCL1A+ disease had significantly worse OS (21.6 vs 63.1; p=0.01) and PFS (12.4 vs 50.7; p=0.01) (Table 2). Additionally, CI of NRM (24% vs 3%; p=0.02) and relapse (25% vs 12%; p=0.86) was higher in TCL1A+ PLL. CD4+CD8-, CD4-CD8+, and CD4+CD8+ disease had no difference in survival via either OS or PFS (Table 2) as well as no difference 1-year CI of NRM (11.6 vs 23.5 vs 26.2; p=0.35) and relapse (18.5 vs 23.5 vs 20.0; p=0.67).</div></div><div><h3>Conclusions</h3><div>AlloSCT significantly improved outcomes for patients with T-PLL and remains the only curative therapy. OS, PFS, and CI relapse were significantly worse for patients with TCL1A+ T-PLL, MRD positivity, or PR prior to alloSCT. Novel strategies to decrease relapse such as post-alloSCT maintenance therapy to improve outcomes are urgently needed in these patients.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S29-S30"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098562","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.2025.12.023
Sunmin Park MD, PhD , Ni-Chun Tsai MS , Dongyun Yang PhD , Amanda Blackmon DO , Vaibhav Agrawal MD , Brian Ball MD , Hoda Pourhassan MD , Salman Otoukesh MD , Shukaib Arslan MD , Idoroenyi Amanam MD , Paul Koller MD , Ahmed Aribi MD , Peter Curtin MD , Ibrahim Aldoss MD , Andrew Artz MD , Vinod Pullarkat MD , Haris Ali MD , Amandeep Salhotra MD , Pamela S. Becker MD, PhD , Monzr M. Al Malki MD , Ryotaro Nakamura MD
The MAGIC Algorithm probability (MAP), based on serum ST2 and REG3α, predicts acute GVHD-related non-relapse mortality (NRM) as early as 7 days after HCT (Hartwell et al. JCI Insight 2017). We retrospectively analyzed day 7 MAP in 721 patients transplanted in 2021-2024 at City of Hope (Park et al. ASH Abstract 2464, 2025). Among them, 164 (23%) were high-risk (HR) and 557 (77%) were low-risk (LR) with detailed characteristics shown in Table 1. With a median follow-up of 18 months among survivors (n=539), HR patients had higher NRM compared to LR (29.8% vs. 9.5% at 1 year, p<0.001), higher NRM without prior acute GVHD (17.4% vs. 3.7% at 1 year, p<0.001), and lower overall survival (63.8% vs. 84.0% at 1 year, p<0.001), with no difference in relapse or acute GVHD incidence. In multivariable analysis, MAP remained independently associated with NRM (HR 3.4, 95% CI 2.4-5.0, p<0.001). Cause-specific mortality analysis demonstrated higher GVHD-related and non-GVHD-related deaths (primarily infection and organ dysfunction) among HR patients, supporting day 7 MAP as a marker of systemic tissue injury rather than GVHD alone.
To identify clinical determinants of HR MAP, we further evaluated patient and HCT variables. Age, HCT-CI, KPS, disease type, conditioning regimen, donor type, and GVHD prophylaxis were significant in univariable analysis. In multivariable models, older age (each year: HR: 1.012 [1.000 - 1.024), p=0.047), HCT-CI ≥3 (HR: 1.941 [1.332 - 2.829], p<0.001), and unrelated donor (vs matched related) (HR: 2.246 [1.400 - 3.605], p=0.004) remained independently associated with HR MAP (Table 2). Regarding GVHD prophylaxis, PTCy or CNI+MTX, compared with tacrolimus/sirolimus (T/S), was not associated with higher HR MAP incidence, while ruxolitinib with T/S (mainly used in MF/MPN) and abatacept (primarily used in pediatric patients) were independently associated with lower incidence of HR MAP (HR: 0.232 [0.079 - 0.687], p=0.037). Because pre- HCT gut dysbiosis is associated with poor HCT outcomes, we examined pre-HCT broad-spectrum antibiotic exposure as a surrogate, which showed no association with HR MAP or clinical outcomes (NRM, acute GVHD).
In summary, day 7 MAP is a strong, independent predictor of NRM irrespective of the development of acute GVHD. Our data suggest that the tissue vulnerability and resiliency in the organ function (represented by HCT-CI and age) and the magnitude of the initial allo-immune response as seen in matched unrelated donor compared with matched related donor, are key drivers of HR MAP. These findings provide insight into the complex nature of post-transplant NRM and warrant further effort to develop biomarker-guided preemptive strategies to mitigate the risk of GVHD-related NRM as well as non-GVHD-related NRM.
{"title":"Determinants of High-Risk MAGIC Algorithm Probability (MAP) at Day 7 after Allogeneic Hematopoietic Stem Cell Transplantation (HCT)","authors":"Sunmin Park MD, PhD , Ni-Chun Tsai MS , Dongyun Yang PhD , Amanda Blackmon DO , Vaibhav Agrawal MD , Brian Ball MD , Hoda Pourhassan MD , Salman Otoukesh MD , Shukaib Arslan MD , Idoroenyi Amanam MD , Paul Koller MD , Ahmed Aribi MD , Peter Curtin MD , Ibrahim Aldoss MD , Andrew Artz MD , Vinod Pullarkat MD , Haris Ali MD , Amandeep Salhotra MD , Pamela S. Becker MD, PhD , Monzr M. Al Malki MD , Ryotaro Nakamura MD","doi":"10.1016/j.jtct.2025.12.023","DOIUrl":"10.1016/j.jtct.2025.12.023","url":null,"abstract":"<div><div>The MAGIC Algorithm probability (MAP), based on serum ST2 and REG3α, predicts acute GVHD-related non-relapse mortality (NRM) as early as 7 days after HCT (Hartwell et al. <em>JCI Insight</em> 2017). We retrospectively analyzed day 7 MAP in 721 patients transplanted in 2021-2024 at City of Hope (Park et al. ASH Abstract 2464, 2025). Among them, 164 (23%) were high-risk (HR) and 557 (77%) were low-risk (LR) with detailed characteristics shown in Table 1. With a median follow-up of 18 months among survivors (n=539), HR patients had higher NRM compared to LR (29.8% vs. 9.5% at 1 year, p<0.001), higher NRM without prior acute GVHD (17.4% vs. 3.7% at 1 year, p<0.001), and lower overall survival (63.8% vs. 84.0% at 1 year, p<0.001), with no difference in relapse or acute GVHD incidence. In multivariable analysis, MAP remained independently associated with NRM (HR 3.4, 95% CI 2.4-5.0, p<0.001). Cause-specific mortality analysis demonstrated higher GVHD-related and non-GVHD-related deaths (primarily infection and organ dysfunction) among HR patients, supporting day 7 MAP as a marker of systemic tissue injury rather than GVHD alone.</div><div>To identify clinical determinants of HR MAP, we further evaluated patient and HCT variables. Age, HCT-CI, KPS, disease type, conditioning regimen, donor type, and GVHD prophylaxis were significant in univariable analysis. In multivariable models, older age (each year: HR: 1.012 [1.000 - 1.024), p=0.047), HCT-CI ≥3 (HR: 1.941 [1.332 - 2.829], p<0.001), and unrelated donor (vs matched related) (HR: 2.246 [1.400 - 3.605], p=0.004) remained independently associated with HR MAP (Table 2). Regarding GVHD prophylaxis, PTCy or CNI+MTX, compared with tacrolimus/sirolimus (T/S), was not associated with higher HR MAP incidence, while ruxolitinib with T/S (mainly used in MF/MPN) and abatacept (primarily used in pediatric patients) were independently associated with lower incidence of HR MAP (HR: 0.232 [0.079 - 0.687], p=0.037). Because pre- HCT gut dysbiosis is associated with poor HCT outcomes, we examined pre-HCT broad-spectrum antibiotic exposure as a surrogate, which showed no association with HR MAP or clinical outcomes (NRM, acute GVHD).</div><div>In summary, day 7 MAP is a strong, independent predictor of NRM irrespective of the development of acute GVHD. Our data suggest that the tissue vulnerability and resiliency in the organ function (represented by HCT-CI and age) and the magnitude of the initial allo-immune response as seen in matched unrelated donor compared with matched related donor, are key drivers of HR MAP. These findings provide insight into the complex nature of post-transplant NRM and warrant further effort to develop biomarker-guided preemptive strategies to mitigate the risk of GVHD-related NRM as well as non-GVHD-related NRM.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S7-S8"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098632","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.2025.12.041
Anne Archer MPH, MSW , Eric Davis MPH , Gaurav Varma MD, MSPH , Luzmary Alvarez MHA , Tenzin Yingsal BS , Nora Chokr MD , Alexandra Gomez Arteaga MD , Sebastian Mayer MD , Tsiporah B. Shore MD , Joshua Fein MD , Juliet N. Barker MBBS (Hons), FRACP
<div><h3>Introduction</h3><div>While HLA-mismatched URD & cord blood (CB) grafts extend allograft access, searches & graft procurement can be expensive, especially if multiple URDs must be pursued. Double unit cord blood (dCB) grafts are also costly although domestic units are increasingly already confirmatory typed & are immediately available.</div></div><div><h3>Methods</h3><div>We analyzed costs of URD/ CB searches with confirmatory typing (CT) & the total cost of graft procurement using NMDP charges incorporating the indirect costs of search coordinator effort. To identify trends over time, URD searches conducted 1/2022-6/2025 were evaluated; dCB searches were analyzed 9/2023-6/2025 since our Center’s adoption of dCB transplant (dCBT).</div></div><div><h3>Results</h3><div>354 pts underwent URD search with donor CT, whereas 43 pts underwent CB search/CT (or hold if units previously typed at high-resolution). Accounting for the number of URDs or CB units pursued & coordinator time, total costs of URD search/CT was much higher than for search/CT (or hold) for CB units, $7,076 vs $1,693, respectively (<strong>Table 1A</strong>).</div><div>Of the 131 pts who underwent URD transplant, a median of 8 URDs were CT’d, & a median 2 underwent workup. Median URD graft cost was $47,264, but median total procurement cost (including URD CT & workup costs) was $67,851. In the 19 pts who underwent dCBT, a median of 4 units were evaluated, with median graft cost of $106,820, & median total procurement cost of $109,362 (<strong>Table 1B</strong>). In an additional 82 pts who underwent URD CT with donor workup (median 2) but did not undergo URD transplant, the median total URD evaluation cost was $11,515 (<strong>Table 1B</strong>). Analysis of searches over time revealed URD procurement costs are increasing by an average of ∼$5000/year, whereas dCB costs have not (<strong>Fig 2</strong>).</div></div><div><h3>Conclusions</h3><div>Our findings have major implications for center search strategy & financial stewardship. Centers should consider the increasing costs of URD CT +/- workup, & the recently instituted fees for donor collection date changes, especially if the pt is not transplanted, as many of these costs may not be reimbursed. URD procurement cost is increasing & the indirect costs of coordinator time will increase if multiple URDs must be pursued for workup. Although dCB grafts are expensive, benefits are realized as CT costs are not increasing, domestic units are now often already typed at high-resolution & have immediate availability. Interestingly, our data suggest that single CB units may be more cost-effective alternatives to URD grafts. Future analyses should model potential cost savings associated with refinements in search strategy. Moreover, modeling in pts suitable for CBT should assess the impact of immediate transplant vs the cost of delay while pursuing an URD, especially in non-European pts who
{"title":"Increasing Costs of Unrelated Donor (URD) Graft Procurement: Implications for Transplant Center Search Strategy & Financial Stewardship","authors":"Anne Archer MPH, MSW , Eric Davis MPH , Gaurav Varma MD, MSPH , Luzmary Alvarez MHA , Tenzin Yingsal BS , Nora Chokr MD , Alexandra Gomez Arteaga MD , Sebastian Mayer MD , Tsiporah B. Shore MD , Joshua Fein MD , Juliet N. Barker MBBS (Hons), FRACP","doi":"10.1016/j.jtct.2025.12.041","DOIUrl":"10.1016/j.jtct.2025.12.041","url":null,"abstract":"<div><h3>Introduction</h3><div>While HLA-mismatched URD & cord blood (CB) grafts extend allograft access, searches & graft procurement can be expensive, especially if multiple URDs must be pursued. Double unit cord blood (dCB) grafts are also costly although domestic units are increasingly already confirmatory typed & are immediately available.</div></div><div><h3>Methods</h3><div>We analyzed costs of URD/ CB searches with confirmatory typing (CT) & the total cost of graft procurement using NMDP charges incorporating the indirect costs of search coordinator effort. To identify trends over time, URD searches conducted 1/2022-6/2025 were evaluated; dCB searches were analyzed 9/2023-6/2025 since our Center’s adoption of dCB transplant (dCBT).</div></div><div><h3>Results</h3><div>354 pts underwent URD search with donor CT, whereas 43 pts underwent CB search/CT (or hold if units previously typed at high-resolution). Accounting for the number of URDs or CB units pursued & coordinator time, total costs of URD search/CT was much higher than for search/CT (or hold) for CB units, $7,076 vs $1,693, respectively (<strong>Table 1A</strong>).</div><div>Of the 131 pts who underwent URD transplant, a median of 8 URDs were CT’d, & a median 2 underwent workup. Median URD graft cost was $47,264, but median total procurement cost (including URD CT & workup costs) was $67,851. In the 19 pts who underwent dCBT, a median of 4 units were evaluated, with median graft cost of $106,820, & median total procurement cost of $109,362 (<strong>Table 1B</strong>). In an additional 82 pts who underwent URD CT with donor workup (median 2) but did not undergo URD transplant, the median total URD evaluation cost was $11,515 (<strong>Table 1B</strong>). Analysis of searches over time revealed URD procurement costs are increasing by an average of ∼$5000/year, whereas dCB costs have not (<strong>Fig 2</strong>).</div></div><div><h3>Conclusions</h3><div>Our findings have major implications for center search strategy & financial stewardship. Centers should consider the increasing costs of URD CT +/- workup, & the recently instituted fees for donor collection date changes, especially if the pt is not transplanted, as many of these costs may not be reimbursed. URD procurement cost is increasing & the indirect costs of coordinator time will increase if multiple URDs must be pursued for workup. Although dCB grafts are expensive, benefits are realized as CT costs are not increasing, domestic units are now often already typed at high-resolution & have immediate availability. Interestingly, our data suggest that single CB units may be more cost-effective alternatives to URD grafts. Future analyses should model potential cost savings associated with refinements in search strategy. Moreover, modeling in pts suitable for CBT should assess the impact of immediate transplant vs the cost of delay while pursuing an URD, especially in non-European pts who","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S23-S24"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098633","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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