Transplantation and Cellular Therapy最新文献

{"title":"Narsoplimab Treatment for Hematopoietic Cell Transplant Associated Thrombotic Microangiopathy (TA-TMA) – Real World Outcomes from an Expanded Access Program","authors":"Michelle Long Schoettler MD, MS , Narinder Nangia PhD , Miguel Angel Perales MD , Rafael F. Duarte MD, PhD , Dr. Andreas Grauer MD , Alessandro Rambaldi MD","doi":"10.1016/j.jtct.2025.01.058","DOIUrl":"10.1016/j.jtct.2025.01.058","url":null,"abstract":"<div><h3>Background</h3><div>TA-TMA is a common, severe complication of HCT driven by endothelial damage and complement dysregulation. In a pivotal trial, the MASP-2 inhibitor narsoplimab resulted in a 61% response rate in adults with TA-TMA. This study's objective is to report overall survival (OS) of narsoplimab-treated TA-TMA patients via an expanded access program (EAP).</div></div><div><h3>Methods</h3><div>All EAP allogeneic HCT recipients treated for TA-TMA from October 15, 2017 to October 16, 2023 (data lock point) were included. Per FDA regulations, study enrollment required all the following: FDA authorization, company approval, IRB approval, and informed consent. Inclusion criteria included TA-TMA, defined by thrombocytopenia and evidence of microangiopathy. Exclusion criteria included malignant hypertension and uncontrolled infection. The protocol recommended narsoplimab intravenous dosing (<50 kg, 4 mg/kg; ≥50 kg, 370 mg) twice weekly for a minimum of 8 weeks. SAS 9.4 (Cary, NC) was used to perform the survival data analysis, which began at the time of TA-TMA diagnosis.</div></div><div><h3>Results</h3><div>128 allogeneic recipients (Full Analysis Set, FAS) were enrolled: 77 adults, median age 51.7 yrs (range 19 – 72), and 51 children, median age 10.1 yrs (range 0 – 18); 67 were male (52.3%). Median time of TA-TMA diagnosis was 98 days post HCT (range 0 – 1042). Risk stratification data were available in 102 patients of whom 100 (98.0%) – the High-Risk Analysis Subset (HRAS) <strong>–</strong> were confirmed to have had ≥1 HR feature with 80 (80.0%) having ≥2 <strong>(</strong>Schoettler et al. TCT 2023)<strong>.</strong> HR features were captured only at time of enrollment; with multi-organ failure (n=87, 87.0%) and acute GVHD (n= 40, 40.0%) as the most reported. In the HRAS cohort, 36 (36.0%) patients were confirmed to have failed eculizumab, with some failing >1 alternative therapy regimen prior to initiating narsoplimab.</div><div>The FAS cohort (n=128) received a median of 9 narsoplimab doses (range 1 – 170), with median follow up of 3.2 months (range 0.1 – 38.5). 1-yr OS across all patients in the FAS cohort was 51.1%, 50.1% in adults and 52.6% in children. For those receiving narsoplimab as front-line therapy, 1-yr OS was 54.2% (52.1% in adults, 60.0% in children).</div><div>In the HRAS cohort (n=100), 1-yr OS across all HR patients was 56.1%, 53.4% in adults and 59.7% in children (<strong>Fig 1</strong>). In this HR group, 14 (14.0%) adults and 22 (22.0%) children had failed prior TA-TMA-directed therapy and received narsoplimab as second-line therapy, with 1-yr OS of 46.9% and 46.9%, respectively (<strong>Fig 2A,2B</strong>).</div></div><div><h3>Discussion</h3><div>In a large EAP including children and adults with high-risk TA-TMA, survival of front-line therapy with narsoplimab mirrored the pivotal trial and exceeded 50%. Further, patients who failed prior TA-TMA therapy had OS rates >45% – historically survival in n","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Page S25"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488160","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}

{"title":"Adapted Anthracycline-Free Sequential Reduced Intensity Conditioning Regimen for Hematopoietic Stem Cell Transplantation: Initial Safety and Efficacy Outcomes.","authors":"Debabrata Mohapatra MD, DM ,&nbsp;Ranjit Kumar Sahoo ,&nbsp;Sabitha Paramasivam ,&nbsp;Sushant Chib","doi":"10.1016/j.jtct.2025.01.030","DOIUrl":"10.1016/j.jtct.2025.01.030","url":null,"abstract":"<div><h3>Background</h3><div>Myeloablative-conditioning (MAC) regimens have their own limitations of toxicity, demanding supportive-care requirements in resource-constrained settings as well as poor tolerance in elderly. We designed a novel conditioning-regimen, developed on the principles of sequential-reduced-intensity-conditioning (RIC).</div></div><div><h3>Method</h3><div>The modified FLAG-based sequential-RIC comprised of lower (non-myeloablative) doses of busulfan, cyclophosphamide (only in haploidentical settings) after initial cytoreductive-phase of FLAG-based regimen (<strong>Figure 1</strong>). Graft-versus-host-disease(GVHD) prophylaxis included: ATLG, cyclosporin, mycophenolate-mofetil and methotrexate.</div><div>Additional adaptations were: 1) Lower-dose ATLG (10mg/kg) and fludarabine (120mg/m²) to reduce viral/fungal infections. 2) Rituximab-100mg on Day+4, as EBV-prophylaxis. 3) Low-dose methylprednisolone from Day4-Day30 as additional GVHD-prophylaxis in haploidentical-settings. 4) Idarubicin replaced by etoposide and venetoclax. 5) Premptive donor-lymphocyte-infusion(DLI) on rising/persistent MRD.</div></div><div><h3>Results</h3><div>Total 28 patients were enrolled between July 2023 to July 2024. Majority were males (75%) and were AML (71.4%) with median age of 31(16-66) years. Ten(35.7%), 7(25%) and 11(39.3%) patients were transplanted in CR1, CR2 and active disease respectively. While 16(57.1%) patients had matched-related-donors (MRD), 12(42.9%) had haploidentical-donors. Sources of graft were either sibling (89.3%) or father (10.7%). After peripheral-blood-stemcell (PBSC) mobilization, median yield of CD34-cells was 21.1(3-42.8)million/kg and CD3 was 415.6(141-1078.5) million/kg. Median CD34-cell dose was 9.5(3-18.8) million/kg and CD3 cell dose 170(36-630) million/kg.</div><div>Neutrophil engraftment occurred at median 12.5 (8-20) days and platelet engraftment occurred at 16 (11-37) days. While febrile neutropenia was universal, 22 (78.6%) patients had culture-positive bacterial sepsis. Other toxicity outcomes are given in <strong>Table1</strong>. Acute and chronic graft-versus-host-disease (GVHD) occurred in 6 and 5 cases respectively. Duration of median follow-up was 117 (11-410) days. Disease-free-survival at 3 months and 6 months were 91.2% (95%CI: 68.9-97.7) and 76.9% (95%CI: 48.1-91.1), while non-relapse mortality(NRM) at 6 months was 11.1% (95%CI: 8.5-30.1) (<strong>Figure 2</strong>). Pre-transplant remission status (<em>p</em>=0.78) and type of donor (<em>p</em>=0.27) did not affect survival.</div></div><div><h3>Conclusions</h3><div>In this preliminary report, we find that the adapted sequential-RIC regimen appears safe, with promising short-term efficacy, albeit high infection rates. Long term follow-up is ongoing.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages S17-S18"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488188","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}

{"title":"Gene Therapy with Reduced-Intensity Conditioning for Sickle Cell Disease","authors":"Stella M. Davies MBBS, PhD, MRCP ,&nbsp;Michael S Grimley MD ,&nbsp;Archana Shrestha PhD ,&nbsp;Amy Shova BS ,&nbsp;Monika Asnani DM, PhD ,&nbsp;Michael Kent MD ,&nbsp;Farzana Sayani ,&nbsp;Charles T Quinn MD, MS ,&nbsp;Omar Niss MD ,&nbsp;Carolyn M. Lutzko PhD ,&nbsp;Parinda A. Mehta MD ,&nbsp;Pooja Khandelwal MD ,&nbsp;Courtney Little BSN ,&nbsp;Sharat Chandra MD ,&nbsp;Sydney Felker PhD ,&nbsp;Mengna J. Chi PhD ,&nbsp;Theodosia A. Kalfa MD, PhD ,&nbsp;Jennifer Knight-Madden MBBS, PhD ,&nbsp;Paritha Arumugam PhD ,&nbsp;Kristie N. Ramos MD ,&nbsp;Punam Malik MA","doi":"10.1016/j.jtct.2025.01.008","DOIUrl":"10.1016/j.jtct.2025.01.008","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Autologous transplantation of gene-modified cells for treatment of sickle cell disease (SCD) involves myeloablative conditioning, with associated cytopenias, toxicities and long hospitalization. We report the first successful demonstration of gene therapy using reduced-intensity conditioning (RIC) for SCD, made possible with an enhanced lentiviral vector and melphalan dosing modified by pharmacokinetics&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To evaluate gene therapy with RIC for SCD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We report seven patients treated in a first-in-human Phase 1/2 study for SCD using RIC transplant (melphalan 140mg/m&lt;sup&gt;2&lt;/sup&gt;) of autologous HSCs genetically modified with a lentiviral vector (GbG&lt;sup&gt;M&lt;/sup&gt;) encoding a modified γ-globin gene that expresses a potent anti-sickling fetal hemoglobin, HbF&lt;sup&gt;G16D&lt;/sup&gt; (ClinicalTrials.gov NCT02186418). Melphalan pharmacokinetics were performed to identify optimal area under the curve (AUC) to maximize engraftment of gene-modified cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Seven patients received gene therapy as described in &lt;strong&gt;Figure 1&lt;/strong&gt;. Minimum duration of follow-up is 2 years (range 2-7 years). No chemotherapy or product-related serious adverse events other than expected cytopenias were reported. The gene therapy product had relatively rich abundance of clones and engraftment was polyclonal with no evidence of clonal dominance on vector integration site analysis after gene transfer. All seven patients demonstrated sustained HbF&lt;sup&gt;G16D&lt;/sup&gt; expression with &gt;80% reduction in severe vaso-occlusive events (VOE) (&lt;strong&gt;Figure 2A,B).&lt;/strong&gt; Melphalan pharmacokinetics were performed after a single dose of 140 mg/m&lt;sup&gt;2&lt;/sup&gt; and melphalan exposure is shown in &lt;strong&gt;Figure 2C&lt;/strong&gt;. Patient 2 had reduced melphalan exposure due to renal hyperfiltration (estimated GFR = 200 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt;), which was associated with lower engraftment of transduced cells. Therefore, patients 6 and 7 received melphalan dosing adjusted for GFR, hematocrit and lean body mass, based on published melphalan PK modeling. As a result, six of seven patients had what appears to be adequate RIC melphalan exposure with melphalan AUC &gt; 6.7 mg·h/L. All six demonstrated stable engraftment with a median vector copy number of 74% (range, 55-99%) compared to the infused product in peripheral blood at 6-12 months (&lt;strong&gt;Figure 2C&lt;/strong&gt;). Median time to platelet engraftment was 20 days (35-36 days reported after busulfan) and to neutrophil engraftment 16 days (20-27 days reported after busulfan). Grade 4 thrombocytopenia was present a median of 5 days and grade 4 neutropenia a median of 8 days (&lt;strong&gt;Figure 3A,B&lt;/strong&gt;). Median length of hospital stay was 24 days (range 17-32 days), shorter than 35 days (range 26-65 days) reported with busulfan.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Translation of sickle cell gene therapy to middle and low ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages S2-S3"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488366","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}

{"title":"CD33 Microchimerism Assessment By Alloheme Predicts Early Relapse in Patients with AML/MDS—Interim Results from the Acrobat Multicenter Study.","authors":"Monzr M. Al Malki MD ,&nbsp;Ronald M. Sobecks MD ,&nbsp;Corey S. Cutler MD MPH ,&nbsp;Ran Reshef MD ,&nbsp;Iskra Pusic MD, MSCI ,&nbsp;Nelli Bejanyan MD ,&nbsp;Sagar S. Patel MD ,&nbsp;Arpita P. Gandhi MD ,&nbsp;Vamsi Kota MD ,&nbsp;M. Nabeel Rajeh MD ,&nbsp;Piyanuch Kongtim MD, PhD ,&nbsp;Ling Shen PhD ,&nbsp;Nishant Dwivedi MD, PhD ,&nbsp;Ashish S Kothari MD, MS ,&nbsp;Stefan O. Ciurea MD","doi":"10.1016/j.jtct.2025.01.013","DOIUrl":"10.1016/j.jtct.2025.01.013","url":null,"abstract":"<div><h3>Introduction</h3><div>AlloHeme® micro chimerism test is a novel NGS method of chimerism detection after HCT with a limit of detection (LOD) of 0.04% for unrelated donors and up to 0.07% for related donors. We present interim results of the ACROBAT study (NCT04635384) evaluating the role of micro-chimerism in predicting relapse in post-allo HCT patients with AML, ALL, or MDS.</div></div><div><h3>Methods</h3><div>A total of 287 subjects (163 AML, 66 MDS, 58 ALL) across 11 US sites received allo-HCT and periodic testing with the AlloHeme® micro chimerism test on whole blood, CD33, and CD3 sorted cells at 14 time-points post-HCT (weeks 4, 6, 8, 10, 12; months 4, 5, 6, 9, 12, 15, 18, 21, and 24). Interim analyses from the AML/MDS sub-group, with 235 patients, a median (IQR) follow-up of 14 months (9.3 – 18.2), 17% relapses, and 23% non-relapse mortality are presented.</div><div>Increasing micro-chimerism (iMC) was defined as ≥0.2% increase in recipient chimerism between two consecutive time points. Complete chimerism (CC) was defined as donor chimerism ≥99.8% at 3 months post-HCT. Relapses were defined as per CIBMTR criteria.</div></div><div><h3>Results</h3><div>Table 1 presents the demographics and disease characteristics of the AML/MDS subgroup. CD33 iMC was the most informative and those results are presented.</div><div>3- and 6-month landmark analyses demonstrated significantly higher relapse incidence in subjects with iMC compared with non-iMC (p-values 0.016 and &lt;0.001, respectively) (Figure 1). A time-varying risk effect model (TVEM) model with iMC as a time-varying variable and non-relapse mortality as a competing risk for relapse demonstrated a hazard ratio (HR) of 35.2 for relapse (CI = 15.5, 80.3; p&lt;0.001) (Table 2). iMC ≥0.2% demonstrated a sensitivity of 93%, specificity of 76%, negative predictive value of 98%, and positive predictive value of 47% for relapse prediction. The median lead time from iMC to relapse was 50 days (IQR – 27,77 days) among subjects in whom iMC was detected before the relapse event (n = 25, 63% of relapses).</div><div>While considering the CD33 CC status, subjects who never achieved CC (Never CC, n=30) had a cause-specific HR of 12.2 (CI = 4.1, 35.7) for relapse compared to those who achieved CC (n=199). Patients who achieved CC and subsequently lost it (Lost CC, n = 60) had an HR of 27.5 (CI = 10.9, 69.4) compared to those who maintained their CC status (n=139) in the TVEM model. The median lead time from loss of CC to relapse for the lost CC sub-group was 153 days (n=27, 68% of relapses).</div></div><div><h3>Conclusion</h3><div>Interim analyses of the ACROBAT study data at 14-month median follow-up suggest that micro chimerism using AlloHeme is an accurate and sensitive test for monitoring relapse in post-alloHCT AML and MDS patients with a clinically meaningful lead time to relapse prediction.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Page S6"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488370","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}

{"title":"Ciltacabtagene Autoleucel (Cilta-cel) Vs Standard of Care (SoC) in Patients with Lenalidomide (Len)-Refractory Multiple Myeloma (MM) after 1–3 Lines of Therapy: Minimal Residual Disease (MRD) Negativity in the Phase 3 Cartitude-4 Trial","authors":"Rakesh Popat ,&nbsp;Albert Oriol ,&nbsp;Michele Cavo ,&nbsp;Lionel Karlin ,&nbsp;Irit Avivi ,&nbsp;Wilfried Roeloffzen ,&nbsp;Seok Jin Kim ,&nbsp;Brea Lipe ,&nbsp;Noffar Bar ,&nbsp;Noemi Horvath ,&nbsp;Andrew Spencer ,&nbsp;Chang-Ki Min ,&nbsp;Diana Chen ,&nbsp;Quanlin Li ,&nbsp;Katherine Li ,&nbsp;Ana Slaughter ,&nbsp;Carolina Lonardi ,&nbsp;Nina Benachour ,&nbsp;Arnab Ghosh ,&nbsp;Martin Vogel ,&nbsp;Yi Lin MD, PhD","doi":"10.1016/j.jtct.2025.01.047","DOIUrl":"10.1016/j.jtct.2025.01.047","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Cilta-cel is approved for the treatment (tx) of patients (pts) with len-refractory MM after ≥1 line based on results of the phase 3 CARTITUDE-4 trial (NCT04181827) showing significantly improved progression-free survival (PFS) vs SoC (hazard ratio [HR], 0.26; &lt;em&gt;P&lt;/em&gt;&lt;0.0001 [protocol-specified weighted analysis]) at the first interim analysis (15.9-month [mo] median follow-up [MFU]) and significant improvements in overall survival (OS) vs SoC (HR, 0.55; &lt;em&gt;P&lt;/em&gt;=0.0009) at the second interim analysis. We report MRD negativity results from a second interim analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Pts were assigned to cilta-cel or SoC (pomalidomide, bortezomib, dexamethasone [PVd]/daratumumab, pomalidomide, dexamethasone [DPd]). Pts in the cilta-cel arm underwent apheresis and received bridging therapy (PVd/DPd) followed by cilta-cel infusion (target dose, 0.75 × 10&lt;sup&gt;6&lt;/sup&gt; CAR+ viable T cells/kg) 5–7 days (d) after the start of lymphodepletion. MRD was assessed via next-generation sequencing (clonoSEQ v2.0; Adaptive Biotechnologies) at d 56 and 6, 12, 18, and 24 mo post infusion in the cilta-cel arm; cycle 1 d 1 in the SoC arm; and in both arms at suspected complete response or better (≥CR) and yearly until progression/start of subsequent therapy in pts in ≥CR. MRD negativity ≥12 mo apart without MRD positivity in between was considered sustained MRD negativity (10&lt;sup&gt;-5&lt;/sup&gt;).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;419 pts were randomized (intent-to-treat [ITT] set; cilta-cel, n=208; SoC, n=211); MFU was 33.6 mo as of May 1, 2024. 145 pts in the cilta-cel arm and 103 in the SoC arm were MRD-evaluable (10&lt;sup&gt;-5&lt;/sup&gt;). MRD-negativity rates (10&lt;sup&gt;−5&lt;/sup&gt;) in the ITT set and the MRD-evaluable subset were higher with cilta-cel vs SoC (Table 1). Across subgroups, cilta-cel vs SoC consistently increased overall MRD-negativity rates. In the ITT set, 48% of the cilta-cel arm achieved MRD negativity by d 56, with the MRD-negative rate rising to 60% by 6 mo post cilta-cel infusion. Overall MRD-negativity rates (10&lt;sup&gt;−6&lt;/sup&gt;) and rates of overall and 12-mo MRD-negative (10&lt;sup&gt;-5&lt;/sup&gt;) ≥CR were higher with cilta-cel vs SoC. Median PFS for pts with 12-mo MRD-negative ≥CR was not reached (NR; 95% CI, not estimable [NE]–NE) for cilta-cel and 37.8 mo (95% CI, 25.0–NE) for SoC; median OS was NR (95% CI, NE–NE) and NR (95% CI, 37.8 mo–NE), respectively. Sustained MRD-negativity rates were higher with cilta-cel vs SoC (Table 2). Overall MRD negativity at 10&lt;sup&gt;−5&lt;/sup&gt; was achieved by 129/176 (73%) pts who received cilta-cel as study tx (89% of 145 evaluable pts).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;At 33.6-mo MFU in CARTITUDE-4, cilta-cel vs SoC significantly increased overall MRD-negativity rates, with pts achieving MRD negativity rapidly post cilta-cel. These data underscore the benefit of cilta-cel, which led to significant increases vs SoC in rates of MRD-negative ≥CR and sustained MRD negativity ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Page S35"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488449","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}

{"title":"A CD33-Deleted Allograft (Trem-cel) Enables Post-Hematopoietic Cell Transplant (HCT) Maintenance Dosing of Gemtuzumab Ozogamicin (GO) with Therapeutic Levels of Drug Exposure and Low Hematologic and Hepatic Toxicity in Patients with High-Risk Acute Myeloid Leukemia (AML)","authors":"John F. DiPersio MD, PhD ,&nbsp;Guenther Koehne M.D., PhD ,&nbsp;Nirali N. Shah MD, MHSc ,&nbsp;Alain Mina MD ,&nbsp;Lea Bernard MD ,&nbsp;Hyung C. Suh MD, PhD ,&nbsp;Divya Koura MD ,&nbsp;Miguel Angel Perales MD ,&nbsp;Roni Tamari MD ,&nbsp;Muhammad Umair Mushtaq MD ,&nbsp;Joseph E. Maakaron MD ,&nbsp;Vanessa E Kennedy MD ,&nbsp;Lori S. Muffly MD ,&nbsp;Sagar S. Patel MD ,&nbsp;Michael Loken PhD ,&nbsp;Chad Hudson MD, PhD ,&nbsp;Darren Stanizzi BA ,&nbsp;Melissa Lee-Sundlov PhD ,&nbsp;Sanjana Thosar PhD ,&nbsp;Sharon L. Hyzy MS ,&nbsp;Brenda Cooper MD","doi":"10.1016/j.jtct.2025.01.098","DOIUrl":"10.1016/j.jtct.2025.01.098","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Maintenance therapy post-HCT is a strategy to reduce AML relapse, however use of GO (Mylotarg&lt;sup&gt;TM&lt;/sup&gt;), an anti-CD33 antibody-drug conjugate, for this purpose is limited by hepato- and hematologic toxicity. Tremtelectogene empogeditemcel (trem-cel, formerly VOR33) is a hematopoietic stem and progenitor cell product produced by CRISPR/Cas9 gene-editing to delete CD33 from CD34+ cells allowing CD33-directed targeting of leukemia while sparing the donor graft.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;VBP101 (NCT04849910) is a Phase 1/2 trial testing safety of trem-cel followed by GO maintenance for patients with CD33+ AML or MDS with high-risk features for relapse post-HCT. Patients must have an 8/8 HLA-matched donor. Donor CD34+ cells are isolated from G-CSF/plerixafor-mobilized peripheral blood. After ∼60 days post-myeloablative HCT with trem-cel, patients begin maintenance therapy with GO in a 3+3 dose escalation with 0.5, 1 and 2 mg/m&lt;sup&gt;2&lt;/sup&gt; doses given every 28 days for 4-8 cycles.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;18 patients received trem-cel with a median dose of 8.71 × 10&lt;sup&gt;6&lt;/sup&gt; CD34+ cells/kg (2.62-12.44) and CD33 editing efficiency median 89% (71-94%). All patients achieved primary neutrophil engraftment, with a median of 9 days (8-12d). Platelet recovery occurred at a median of 16 days (13-22d) (Fig 1). D28 assessment showed full donor myeloid chimerism in all evaluable patients and a mean of 93.1% (73-99%) of myeloid cells lacked CD33 expression by flow cytometry.&lt;/div&gt;&lt;div&gt;Pharmacokinetic analysis demonstrated dose proportional AUC exposures in trem-cel patients in all cohorts, with the 2 mg/m&lt;sup&gt;2&lt;/sup&gt; doses of GO similar to 9 mg/m&lt;sup&gt;2&lt;/sup&gt; therapeutic doses in relapsed/refractory (R/R) AML patients. C&lt;sub&gt;max&lt;/sub&gt;, after 2 mg/m&lt;sup&gt;2&lt;/sup&gt; doses in trem-cel patients, was comparable to R/R AML patients receiving 4-5 mg/m&lt;sup&gt;2&lt;/sup&gt; doses, suggesting a reduced risk of hepatotoxicity.(Fig 2)&lt;/div&gt;&lt;div&gt;No Gr 4 neutropenia was observed and only a single episode of Gr 4 thrombocytopenia was reported in 40 GO cycles administered (Fig 3). No elevation of transaminases beyond transient Gr 1 was observed during GO cycles. CD33 negative myeloid cells increased from a mean 93.2% (76-99%) to 98.2% (95-99.9%) after the first GO cycle suggesting enrichment for CD33-edited cells which was increased and sustained through subsequent cycles. With a median follow-up of ∼6 months, 4 patients relapsed (2 prior to GO dosing) and the median RFS has not been reached. Enrollment is ongoing at the 2 mg/m&lt;sup&gt;2&lt;/sup&gt; dose.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Preliminary results from VBP101 show trem-cel rapidly engrafts, sustains hematopoiesis with persistent myeloid absence of CD33 and protects from prolonged deep GO-associated cytopenias. GO exposures correlate with higher doses seen in R/R AML patients, likely due to reduction CD33-mediated clearance and supports an increased therapeutic window. These da","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages S61-S62"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488476","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}

{"title":"Post-Transplant Cyclophosphamide-Based Graft-Versus-host Disease Prophylaxis Following Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation Using Myeloablative Conditioning – Results from the Access Trial","authors":"Monzr M. Al Malki MD ,&nbsp;Stephanie Bo-Subait MPH ,&nbsp;Brent R. Logan PhD ,&nbsp;Janelle Olson PhD ,&nbsp;Erin Leckrone ,&nbsp;Juan (Maggie) Wu MS ,&nbsp;Dr. Heather E. Stefanski MD, PhD ,&nbsp;Dr. Jeffery J. Auletta MD ,&nbsp;Stephen R. Spellman MBS ,&nbsp;Craig Malmberg ,&nbsp;Rachel J Cook MD, MS ,&nbsp;Brian C. Shaffer MD ,&nbsp;Dipenkumar Modi MD ,&nbsp;Farhad Khimani MD ,&nbsp;Karen K Ballen MD ,&nbsp;Alison W. Loren MD, MSCE ,&nbsp;Karilyn T Larkin MD ,&nbsp;Sally Arai MD ,&nbsp;Mahasweta Gooptu MD ,&nbsp;Mehdi Hamadani MD ,&nbsp;Antonio M. Jimenez Jimenez MD","doi":"10.1016/j.jtct.2025.01.105","DOIUrl":"10.1016/j.jtct.2025.01.105","url":null,"abstract":"<div><h3>Introduction</h3><div>Our prior prospective multi-center clinical trial (15-MMUD) reported 72% overall survival (OS) at one year in adult patients with hematological malignancies undergoing myeloablative conditioning (MAC) and bone marrow (BM) grafts from HLA-mismatched unrelated donors (MMUD) and post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (Shaw, J Clin Oncol 2021).</div></div><div><h3>Objectives</h3><div>We sought to determine whether OS in adults receiving mobilized peripheral blood stem cells (PBSC) from MMUD would be comparable.</div></div><div><h3>Methods</h3><div>We conducted a prospective, multi-center Phase II study (NCT04904588) to assess the impact of PTCy-based GVHD prophylaxis on OS following MMUD transplantation in adults and children with advanced hematological malignancies. The study included three strata: two adult cohorts based on conditioning regimen intensity [MAC (N=75) or reduced intensity conditioning (RIC; N= 193)] using PBSC, and one pediatric cohort using MAC and BM (still enrolling). Donors were matched at 4-7/8 HLA-loci (HLA -A, -B, -C, and -DRB1) and ≤ 35 years old. The primary endpoint was OS at one year following transplantation. Here, we report the analysis results of all 75 adult patients enrolled on the MAC PBSC stratum.</div></div><div><h3>Results</h3><div>Eighteen sites enrolled 75 patients with the following demographics: median age of 46 years (range 20-65); 60% male; diagnoses: AML (44%), ALL (39%), MDS (12%), other heme malignancies (5%); Patient race/ethnicity: non-Hispanic white (29%). Donor characteristics included: median age 25y (range 18-34); male (44%); and HLA match level: 7/8: 69%; 6/8: 25%; 5/8: 4%; 4/8: 1%. Conditioning regimens included fludarabine (flu) and busulfan (49%) and flu/TBI (51%). OS at one year post HCT was 84% (95% confidence interval (CI): 73-90%). Secondary endpoints are provided in Table 1.</div></div><div><h3>Conclusion</h3><div>OS observed at one year following MMUD PBSC in patients receiving MAC and PTCy was encouraging and appears similar to historical data in MAC recipients of HLA-matched donor PBSC grafts. Notably, 71% of enrolled patients were non-white or Hispanic. OS compares favorably relative to our prior study using BM grafts. Rates of GVHD and other complications were also in the range of those observed in HLA-matched donor recipients, suggesting MMUD HCT expands access to a potentially life-saving therapy for all patients regardless of ancestry. Accrual to both adult strata of ACCESS is complete, with analysis of the full adult RIC stratum planned for later this year.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Page S67"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488671","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}

{"title":"Results from a Prospective Phase II Clinical Study: High Vs Medium-Intensity Regimens in Patients Undergoing Cord Blood Transplantation","authors":"John N Colgan BMed, MD ,&nbsp;Ted A. Gooley PhD ,&nbsp;Brandon Hadland MD, PhD ,&nbsp;Corinne Summers MD ,&nbsp;Colleen Delaney MD, MSc ,&nbsp;Filippo Milano MD, PhD ,&nbsp;Ann Dahlberg MD","doi":"10.1016/j.jtct.2025.01.018","DOIUrl":"10.1016/j.jtct.2025.01.018","url":null,"abstract":"<div><h3>Introduction</h3><div>We prospectively analyzed outcomes for UCB transplant (UCBT) in a malignant cohort receiving either a high-dose TBI or a medium-intensity conditioning regimen.</div></div><div><h3>Methods</h3><div>From 2006-2023, 132 patients were enrolled on a single-arm, phase II study for patients undergoing UCBT after myeloablative preparative regimen with either cyclophosphamide, fludarabine and 13.2Gy total body irradiation (TBI) (Reg A) or cyclophosphamide, fludarabine, thiotepa and 4Gy TBI (Reg B) for the treatment of hematologic malignancies. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. Kaplan-Meier or cumulative incidence estimates were used to summarize point estimates of overall survival (OS), progression-free survival (PFS), relapse, and non-relapse mortality (NRM). Cox regression was used to compare outcomes between treatment regimens (high-intensity vs. medium-intensity regimens) and between patients with vs. without measurable residual disease (MRD).</div></div><div><h3>Results</h3><div>Median follow-up among 93 survivors was 3.5 years and median age at time of transplant was 20. Fifty-seven of 132 enrolled were female. The most common indications for transplant were acute myeloid leukemia (n=57) and acute lymphoblastic leukemia (n=48). 51 patients received a single cord-blood unit and 81 received double-cord units. 105 patients received Reg A whilst 27 patients received Reg B. Average total nucleated cell dose was 5.42 × 10^7/kg. Median time to engraftment was 21 days with 3 patients experiencing primary graft failure. Incidence of grade III-IV acute GVHD was 20%.</div><div>Estimates of OS, PFS, relapse, and NRM in the entire cohort, the acute leukemia cohort (patients with AML, ALL or myelodysplastic syndrome, n=114) and the pediatric leukemia cohort (patients &lt;/= 21, n=64) are represented in figures 1-3. Table 1 summarizes comparisons for each examined outcome between Regimens B and A for all patients, and between MRD+ and MRD- patients in the acute leukemia cohort.</div></div><div><h3>Discussion</h3><div>The data from this single center prospective trial demonstrate excellent overall outcomes for patients undergoing UCBT. A comparison between the medium-intensity and high-dose TBI regimens yielded numerical increases in the hazard of failure for each outcome, although none were large enough to draw definitive conclusions. In contrast to other stem cell sources, this analysis saw no evidence of increased relapse among patients with MRD relative to those without MRD. These results highlight the utility of UCB as a donor source for HSCT.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Page S10"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488845","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}

{"title":"Manufacturing Characteristics and Early Outcomes of a Tandem aCD22-aCD19 CAR-T Therapy for Childhood and Adult Relapsed/Refractory Acute Precursor B Lymphoblastic Leukemia","authors":"Michaela Su-fern Seng MBBS, FRACP, PhD ,&nbsp;Shui Yen Soh MBBS, MRCPCH ,&nbsp;Francesca Lorraine Lim MD ,&nbsp;William Ying Khee Hwang FRCP, FAMS, MMed, MRCP, MBBS ,&nbsp;Liang Piu Koh MD ,&nbsp;Esther Chan MBBS ,&nbsp;Jia Meng PhD ,&nbsp;Joe P Yeong MBBS, FRCPath, PhD ,&nbsp;Jason Chan MBBS, PhD ,&nbsp;Wing H. Leung MD, PhD","doi":"10.1016/j.jtct.2025.01.020","DOIUrl":"10.1016/j.jtct.2025.01.020","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Real-world data shows that 50% of B-ALL patients with CD19-41BBz-CAR-T and 80% with CD19-28z-CAR-T eventually relapse due to antigen escape or loss of CAR-T persistence. This often necessitates consolidation with haematopoietic stem cell transplant (HSCT) while in post-CAR-T remission, which has significant long-term effects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;To address the limitations of aCD19 CAR-T therapy, we conducted a Phase I/II trial investigating tandem aCD22-aCD19 CAR-T therapy (MB-CART2219.1) for relapsed/refractory (r/r) B-ALL. (NCT 05429905). We hypothesised that simultaneous targeting of CD19 and CD22 would improve leukaemia-free survival (LFS) after CAR-T without needing HSCT consolidation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Patients aged 2 to 75 who had multiply relapsed B-ALL or who had refractory MRD after consolidation chemotherapy were eligible, including those with relapsed extramedullary disease, prior CAR-T or immunotherapy after a washout period. Patients received fludarabine and cyclophosphamide lymphodepletion followed by a single fresh infusion of MB-CART2219.1 manufactured in a 12-day vein-to-vein protocol. We assessed bone marrow disease response by flow-MRD and ddPCR-MRD. We generated knowledge on cellular kinetics and immune signatures of MB-CART2219.1 using multiparameter flow immunophenotyping and single-cell RNA sequencing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Eleven patients (7 paediatric, 4 adults) received MB-CART2219.1 for r/r B-ALL. CAR-T cells were predominantly central and effector memory and minimally exhausted. Mean %CAR+ T cells in the final product was 77.7% (aCD19 CAR) and 82.1% (aCD22 CAR). The primary aims of our phase I study were met in the paediatric cohort, with an RP2D of 2.5 × 10^6/kg CAR+ T cells. Besides CRS, notable severe adverse events included IEC-HLH and delayed cytopenias. No neurotoxicity was reported. Our interim efficacy analysis for Phase I showed a 91% MRD-negative complete remission rate, a 12-month LFS probability of 63.6% ± 14.5% and 12-month overall survival of 77.9% ± 14.1% without transplant consolidation, surpassing historical benchmarks. Multi-omic data provided insights into the MB-CART2219.1 CAR-T product and post-infusion signatures in our responders. A durable clinical response associated favourably with CAR-T product effector signatures (CD62L-, CD27-, CD56+, low Treg), cytotoxic transcriptome (GZMB, IFNG, TNFSF10) and a balanced CD4/8 ratio. Post-infusion, clinical response was associated with CD8+ CART activation signatures at peak expansion and the acquisition of CD127 at day 28.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;MB-CART2219.1 is a promising definitive treatment for multiply relapsed or primary refractory (high MRD) B-ALL. An ongoing Phase II study will confirm the early efficacy and safety results. Multiomic analysis in a representative subset of patients suggests that cytotoxic effector potential of CAR-T is important f","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Page S11"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488846","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}

{"title":"Disparities in Allograft Access in the Era of Post-Transplant Cyclophosphamide (PTCy)-Based Graft-Versus-Host Disease Prophylaxis","authors":"Frances Natalia Cervoni-Curet M.D. ,&nbsp;Denai R. Milton MS ,&nbsp;Ricky Garcia ,&nbsp;Ligny Hunter ,&nbsp;Celina Ledesma BS ,&nbsp;Charles S Martinez BS ,&nbsp;Gabriela Rondon MD ,&nbsp;Yudith Carmazzi ,&nbsp;Kai Cao MD ,&nbsp;Gheath Al-Atrash D.O., Ph.D. ,&nbsp;Yosra M. Aljawai MD ,&nbsp;Amin M. Alousi MD ,&nbsp;Qaiser Bashir MD ,&nbsp;George L. Chen MD ,&nbsp;Chitra M. Hosing MD ,&nbsp;Jin S. Im MD, PhD ,&nbsp;Partow Kebriaei MD ,&nbsp;Issa F. Khouri MD ,&nbsp;David Marin MD ,&nbsp;Rohtesh S. Mehta MD ,&nbsp;Warren B. Fingrut MD","doi":"10.1016/j.jtct.2025.01.080","DOIUrl":"10.1016/j.jtct.2025.01.080","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Although PTCy based GVHD prophylaxis has extended allograft access to patients (pts) from underserved populations, the extent to which disparities in allograft access persist is unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We examined racial &amp; socioeconomic (SES) disparities in graft source/characteristics &amp; time to BMT in all adult 1&lt;sup&gt;st&lt;/sup&gt; allograft recipients 1/2018-6/2024 transplanted for AML, a diagnosis for which BMT is urgent (since 1/2018, our center routinely used PTCy GVHD ppx for adult donor grafts). We defined: 1) low SES as the composite of area deprivation index (ADI) ≥60%, Medicaid/Indigent insurance, &amp;/or pt self report of cost of living/medical expense insecurity; 2) BMT indication date as date of diagnosis if ELN 2017 int/high risk or high risk molecular mutations or 2&lt;sup&gt;o&lt;/sup&gt; AML (n=672), else date of relapse (n=45); &amp; 3) delayed BMT indication to transplant time as ≥180 days. Associations between delayed times to BMT &amp; pt characteristics were evaluated using multivariable logistic regression models.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Of 717 AML pts (median age 57 yrs, range 18-78; 87% received PTCy GVHD ppx), 485 (68%) were White/non-Hispanic &amp; 232 (32%) non-White [49 Black, 97 Hispanic, 81 Asian, 5 Other]. Compared with White pts, fewer older non-White pts were transplanted (median age 60 vs 52 yrs, p&lt;.001).&lt;/div&gt;&lt;div&gt;Examining SES, 225 (31%) pts had low SES by ADI, 33 (5%) by insurance &amp; 29 (4%) by self report. However, each measure classified different pts as low (Fig 1), with 256 (36%) pts having low SES by ≥1 measure (including 53% of Black pts).&lt;/div&gt;&lt;div&gt;By donor type, 199 (28%) pts received HLA-identical related, 345 (48%) 8/8 unrelated donor (URD), 12 (2%) cord blood (CB), 129 (18%) haplo &amp; 32 (4%) 6-7/8 URD grafts. Compared with White pts, non-White pts received &gt;2x as many mismatched grafts (ie haplo/ CB/ 6-7/8 URDs), 40% vs 17%, p&lt;.001. Over half (54%) of Black low SES pts received mismatched grafts. Considering graft characteristics, non-White pts received older adult donors including &gt;2x as many haplos &gt;40 yrs, 39% vs 18%, p=.010.&lt;/div&gt;&lt;div&gt;Overall, 40% of pts faced delays to BMT ≥180 days. Analysis of factors associated with time from BMT indication to transplant revealed marked disparities, with non-White pts more likely to face delays to BMT ≥180 days [OR (95% CI) 1.65 (1.17, 2.33), p=.004], due to the combinations of delays from indication to consult ≥90 days (1.62 (1.11, 2.36), p=.013), consult to financial approval ≥ 45 days (1.59 (1.13, 2.25), p=.008) &amp; financial approval to BMT ≥90 days (1.65 (1.17, 2.32), p=.004). 8/8 URD recipients also faced delays from BMT indication to transplant [1.61 (1.10, 2.35), p=.014] due to delays from financial approval to BMT [1.53 (1.05, 2.21), p=.025]. In subgroup analysis, non-White 6-8/8 URDs faced greatest delays to BMT (Fig 2).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;We demo","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages S49-S50"},"PeriodicalIF":3.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488870","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}