Transplantation and Cellular Therapy最新文献

{"title":"CAR T-cell Consolidation Versus Lenalidomide Maintenance after Autologous Stem Cell Transplant in Multiple Myeloma: A Comparative Analysis of Toxicity and Cost","authors":"Batoul Sadek DO ,&nbsp;Muhammad Saad Waqas MD ,&nbsp;Harry Balanta-Murcia MD ,&nbsp;Tamila L Kindwall-Keller DO ,&nbsp;Jennifer Mason Lobo PhD","doi":"10.1016/j.jtct.2025.12.056","DOIUrl":"10.1016/j.jtct.2025.12.056","url":null,"abstract":"<div><h3>Background</h3><div>Multiple myeloma (MM) is a heterogeneous plasma cell malignancy, with recent therapeutic advances extending the median survival to 8-10 years. Standard of care for eligible patients includes induction chemotherapy followed by autologous stem cell transplant (ASCT) and lenalidomide maintenance. Chimeric antigen receptor T-cell (CAR-T) therapy, approved for relapsed/refractory MM, is a promising cellular immunotherapy approach. This study evaluates and compares clinical efficacy, toxicities, costs, and cost-effectiveness of lenalidomide maintenance versus (vs) CAR-T consolidation after ASCT.</div></div><div><h3>Methods</h3><div>We evaluated the comparative effectiveness and cost-effectiveness of lenalidomide maintenance vs CAR-T consolidation after ASCT in patients achieving <u>&gt;</u>partial response after receiving daratumumab, lenalidomide, bortezomib, and dexamethasone (Dara-VRd). Clinical inputs for lenalidomide maintenance were from phase III trials: CAR-T outcomes were from second-line treatment studies. Post-progression treatments were standard regimens with reduced efficacy in later lines. A Markov model was built in TreeAge Pro Healthcare 2022 using monthly cycles and lifetime horizon from a US payer perspective. Costs/utilities were discounted at 3% annually. Outcomes were assessed using incremental cost-effectiveness ratio (ICER) with a willingness to pay threshold of $250,000/quality-adjusted life year (QALY). Costs included one-time hospitalization costs for inpatient toxicities and ongoing monthly costs for outpatient events. Cost and disutility estimates were sourced from the literature and adjusted to 2025 US dollars.</div></div><div><h3>Results</h3><div>Simulation results demonstrated higher probabilities of grade 3/4 complications with CAR-T consolidation compared to lenalidomide maintenance including infections (26.9% vs 6.5%), anemia (35.6% vs 4.8%), neutropenia (89.9% vs 50.2%), thrombocytopenia (41.3% vs 14.7%), lymphopenia (20.7% vs 9.1%), cytokine release syndrome (CRS) (1.1% vs 0%), and neurotoxicity (2.8% vs 0%). CRS and neurotoxicity were the costliest complications ($74,609 and $113,848). In contrast, lenalidomide maintenance showed higher rates of febrile neutropenia (6.5% vs 0%) and diarrhea (5.2% vs 3.8%), but an overall lower toxicity burden. Disutilities reflected clinical course, with acute events modeled as short-term decrements and chronic toxicities as ongoing quality-of-life losses during active therapy. The overall most effective treatment depended on assumptions for response to therapy and rates of progression.</div></div><div><h3>Conclusion</h3><div>CAR-T consolidation after ASCT is associated with greater toxicity and cost, particularly from CRS and neurotoxicity, whereas lenalidomide maintenance shows a more favorable toxicity profile. These findings highlight the need to integrate toxicity and cost-effectiveness in treatment decisions for newly diagnosed MM.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S34"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098625","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":"KarMMa-3 Subgroup Analysis in Older Patients with Relapsed/Refractory Multiple Myeloma Treated with Idecabtagene Vicleucel","authors":"Sikander Ailawadhi MD ,&nbsp;Bertrand Arnulf MD ,&nbsp;Krina K. Patel MD, MS ,&nbsp;Michele Cavo MD ,&nbsp;Ajay K. Nooka MD, MPH ,&nbsp;Salomon Manier MD, PhD ,&nbsp;Shinsuke Iida MD, PhD ,&nbsp;Sophie Hello PharmD ,&nbsp;Devender Dhanda PhD ,&nbsp;Prachi Ghodke MSc ,&nbsp;Martina Raggi PhD ,&nbsp;Roland Marion Gallois MSc ,&nbsp;Jaclyn Davis MD ,&nbsp;Paula Rodríguez-Otero MD, PhD","doi":"10.1016/j.jtct.2025.12.057","DOIUrl":"10.1016/j.jtct.2025.12.057","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Chimeric antigen receptor (CAR) T-cell therapies are an effective treatment option for patients with relapsed/refractory multiple myeloma (RRMM). Idecabtagene vicleucel (ide-cel) is a B-cell maturation antigen-targeted CAR T-cell therapy approved for patients with RRMM with ≥2 prior lines of therapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;To present a subgroup analysis from the KarMMa-3 trial (NCT03651128) evaluating efficacy and safety outcomes in older and younger patients with RRMM who received ide-cel or standard therapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;KarMMa-3 is an open-label, phase 3 trial of adults with RRMM who received 2-4 prior treatment regimens with disease refractory to the last therapy. Enrolled patients were randomized (2:1) to receive either a one-time infusion of ide-cel or 1 of 5 standard regimens. The efficacy and safety of ide-cel compared with standard regimens were evaluated by age (≥70 vs &lt;70 y). Outcome measures assessed include overall response rate (ORR), progression-free survival (PFS), overall survival (OS), patient-reported quality of life (QoL), and incidence of selected adverse events.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 386 patients were evaluated; 19.3% (49/254) of those receiving ide-cel and 20.5% (27/132) of those receiving standard regimens were aged ≥70 y. Compared with older patients, younger patients receiving ide-cel exhibited more high-risk baseline characteristics, including high-risk cytogenic abnormalities (44.4% vs 32.7%) and triple-class refractory disease (66.8% vs 55.1%).&lt;/div&gt;&lt;div&gt;ORR for patients aged &lt;70 y was 68.8% (95% CI, 62.4%-75.1%) with ide-cel and 41.0% (31.5%-50.4%) with standard regimens (&lt;em&gt;P&lt;/em&gt;&lt;0.0001). Patients aged ≥70 y treated with ide-cel achieved an ORR of 81.6% (95% CI, 70.8%-92.5%) vs 48.1% (29.3%-67.0%) with standard regimens (&lt;em&gt;P&lt;/em&gt;&lt;0.01). Median PFS for patients aged &lt;70 y was longer with ide-cel treatment vs standard regimens (12.5 mo [95% CI, 11.2-15.4] vs 4.2 mo [3.5-5.7]; &lt;em&gt;P&lt;/em&gt;&lt;0.0001). In patients aged ≥70 y, median PFS was 18.9 mo (95% CI, 12.1-24.5) with ide-cel treatment and 5.7 mo (2.2-12.2) with standard regimens (&lt;em&gt;P&lt;/em&gt;&lt;0.01). Median OS was not reached (NR) in older patients in either treatment arm; in younger patients, median OS was 39.5 mo (95% CI, 27.8-NR) with ide-cel and 27.9 mo (20.6-NR) with standard regimens. Incidence of adverse events reported with ide-cel treatment was similar between age groups for cytokine release syndrome, neurotoxicity, and infections. Analyses of patient-reported QoL data and other relevant safety endpoints are ongoing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;In KarMMa-3, older patients derived substantial benefit from ide-cel treatment, demonstrated by longer PFS and a notable ORR compared with standard regimens. Efficacy and safety outcomes were consistent across age groups, reinforcing the potential for durable benefit with a single ide-cel ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S34-S35"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098626","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":"Dosing-Dependent Effects of Post-Transplantation Cyclophosphamide (PTCy) on Human Early Immune Responses: Insights from Single-Cell Analysis","authors":"Natalia S. Nunes PhD ,&nbsp;Jing Bian BS ,&nbsp;Michael C. Kelly PhD ,&nbsp;Maggie Cam PhD ,&nbsp;Christopher G. Kanakry MD","doi":"10.1016/j.jtct.2025.12.071","DOIUrl":"10.1016/j.jtct.2025.12.071","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Based on murine data, we initiated a phase I/II clinical study to reduce PTCy from 50 mg/kg/day on days +3/+4 (Set 1) to 25 mg/kg/day on days +3/+4 (Set 2) or 25 mg/kg on day +4 only (Set 3) along with sirolimus and MMF (both starting day +5) for myeloablative HLA-haploidentical bone marrow HCT. Phase II used the Set 2 dosing and found no grade II-IV acute GVHD events and 13% chronic GVHD requiring systemic therapy, but with faster T-cell recovery and less frequent CMV reactivation and less severe BK virus cystitis compared with Set 1.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Single-cell RNA sequencing was performed fresh in donor PBMCs and marrow on day 0 and in recipient PBMCs on days 0, +3, +5, +7, and +21 for the 19 phase I patients (n=5-7 per Set). Donor- and recipient-derived cells were separated using unique SNPs identified from day 0 samples. Data were batch corrected (Harmony), annotated (Seurat Azimuth), and analyzed in a pseudobulk manner. Alloreactive T cells were defined based either on CITEseq expression of CD69 or CD137 at day +3, +5, and/or +7 or based on matching with donor T-cell clones proliferating against recipient pre-HCT cells in mixed lymphocyte cultures &lt;em&gt;in vitro&lt;/em&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;594,070 cells were captured across 132 patient samples. Alloreactive CD4&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; T cells were trackable and persisted despite PTCy; interestingly, given the HLA-haploidentical setting, alloreactive T cells commonly derived from memory cells in the donor. T-cell receptor diversity was more clonal at day +21 after Set 1 vs. Sets 2/3. Pathway analysis showed donor CD4&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt; T cells, natural killer cells, and monocytes had less DNA damage at days +5/+7 in Sets 2/3 vs. Set 1, an effect also seen within alloreactive T cells. At day +21, CD4&lt;sup&gt;+&lt;/sup&gt; T cells in Sets 2 and 3 had increased Th17 differentiation compared with Set 1, and Set 2 also had increased type I interferon signaling vs. Set 1. Donor CD8&lt;sup&gt;+&lt;/sup&gt; T cells and alloreactive CD8&lt;sup&gt;+&lt;/sup&gt; T cells within Sets 2/3 at days +5/+7/+21 had increases in pathways related both to GVHD but also responses to pathogens when compared to Set 1. Donor monocytes had increased interleukin-10 signaling at day +21 in Set 2 compared with Set 1. Cell chat analyses showed different patterns of cell-cell communications between Sets 2/3 and Set 1, particularly between donor and recipient T cells at day +5/+7 and between donor monocytes and T cells at day +21. Gene correlation network analysis across Sets and timepoints showed consistent associations at days +3, +5, +7, and +21 with non-relapse mortality.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Reducing PTCy dosing results in less DNA damage, increased CD8&lt;sup&gt;+&lt;/sup&gt; T-cell pathways of GVHD and pathogen response, and modulations in cell-cell interactions. Even so, these effects did not increase clinical GVHD, even as they decreased infection. Gene modu","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S45"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098704","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":"Three-Year Efficacy and Longitudinal Safety of Lisocabtagene Maraleucel (liso-cel) in Patients with Third-Line or Later (3L+) Follicular Lymphoma (FL) from TRANSCEND FL","authors":"Sairah Ahmed MD ,&nbsp;Alejandro Martin García-Sancho MD, PhD ,&nbsp;Juan Luis Reguera Ortega MD ,&nbsp;Guillaume Cartron MD, PhD ,&nbsp;Aaron P. Rapoport MD ,&nbsp;Koji Izutsu MD, PhD ,&nbsp;Hervé Ghesquieres MD, PhD ,&nbsp;Hideki Goto MD, PhD ,&nbsp;Jeremy S. Abramson MD, MMSc ,&nbsp;Peter Borchmann MD ,&nbsp;Ulrich Jager MD ,&nbsp;Manali Kamdar MD, MBBS ,&nbsp;Martin Dreyling MD ,&nbsp;Merav Bar MD ,&nbsp;Maria Strocchia PharmD, PhD ,&nbsp;Martina Raggi PhD ,&nbsp;Luciana Bueno MD ,&nbsp;Jessica Papuga PhD ,&nbsp;Silvia Colicino PhD ,&nbsp;Franck Morschhauser MD, PhD","doi":"10.1016/j.jtct.2025.12.079","DOIUrl":"10.1016/j.jtct.2025.12.079","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;In the primary analysis of TRANSCEND FL (NCT04245839), an open-label, pivotal study, liso-cel showed high response rates and favorable safety in patients with R/R FL.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;To report 3-y follow-up (FU) results in patients with 3L+ FL, including efficacy, safety, and longitudinal safety analyses for key AEs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Eligible patients had R/R FL after ≥ 2 prior lines of combination systemic therapy, including an anti-CD20 antibody and an alkylator. Patients received liso-cel after lymphodepleting chemotherapy (LDC). Bridging therapy was allowed with reconfirmation of PET-positive disease before LDC. The primary endpoint was ORR per independent review committee by PET/CT using Lugano 2014 criteria. Secondary endpoints included CR rate, duration of response, PFS, OS, and safety. Additional post hoc analyses included time to next treatment and efficacy by progression of disease ≤ 24 mo from first-line chemoimmunotherapy (POD24) status (yes vs no) and by prior bendamustine exposure before leukapheresis (yes vs no). Incidences of infections, second primary malignancies (SPM), hypogammaglobulinemia, and grade ≥ 3 cytopenia (overall and by lineage) were assessed over time from Days 1–30, at 3-mo intervals until Month 12, at 6-mo intervals until Month 36, and from Month 36 until end of study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;At data cutoff (03/31/2025), 107 patients with 3L+ FL received liso-cel and were evaluable for safety; 103 were efficacy evaluable. Median (range) age was 62 y (23–80); 95 (89%) had Ann Arbor stage III/IV disease; 61 (57%) were high risk per FL International Prognostic Index. Fifty-nine patients (55%) had POD24; 69 (64%) were double refractory to anti-CD20 antibody and an alkylator; 65 (61%) had prior bendamustine exposure.&lt;/div&gt;&lt;div&gt;Median (range) on-study FU was 41.5 mo (0.3–54.0). Response rates were high overall and regardless of POD24 status or prior bendamustine exposure (&lt;strong&gt;Table 1&lt;/strong&gt;).&lt;/div&gt;&lt;div&gt;Treatment-emergent (TE) AE rates were consistent with the primary and 2-y FU analyses. Grade 3 cytokine release syndrome was reported in 1% (no grade 4/5) and grade 3 neurological events in 2% (no grade 4/5). SPMs were reported in 11 patients (10%; 4 additional patients since the 2-y FU analysis; no secondary T-cell malignancies). Grade ≥ 3 infections were reported in 13 (12%) patients, including 7 (7%) in the TE period (≤ 90 d after infusion) and 8 (7%) in the post-TE period (3 more patients since the 2-y analysis). AE incidences over time are shown in &lt;strong&gt;Table 2&lt;/strong&gt;.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In patients with 3L+ FL, a single infusion of liso-cel demonstrated remarkable efficacy, with durable responses and high 3-y survival rates, regardless of POD24 status or prior bendamustine exposure. No new safety signals were identified. Grade ≥ 3 neutropenia and hypogammaglobulinemia decreased over time and severe","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S50-S51"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098750","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":"Landmark Long-Term Remission Achieved with ICG318, a BCMA-CD19 Armored Compound CAR T-cell Therapy, in Refractory Systemic Lupus Erythematosus/Lupus Nephritis with Follow-up Approaching 6 Years","authors":"Ming Hong Ph.D. ,&nbsp;Mingxia Wang M.D. ,&nbsp;Ronghao Zeng M.D. ,&nbsp;Ling Ding M.D. ,&nbsp;Shanzhi He M.D. ,&nbsp;Ting Lan M.S. ,&nbsp;Vincent M. DeStefano B.E. ,&nbsp;Masayuki Wada Ph.D. ,&nbsp;Kevin Pinz M.S. ,&nbsp;Jennifer E. Chow B.S. ,&nbsp;Byeong Hyeok Choi Ph.D. ,&nbsp;Nabil Hagag Ph.D. ,&nbsp;Min Wang M.D. ,&nbsp;Yu Ma M.S. ,&nbsp;Jing Luo M.S. ,&nbsp;Yingwen Liang B.E. ,&nbsp;Ziji Lu M.D. ,&nbsp;Wenli Zhang Ph.D. ,&nbsp;Shihao Ding B.E. ,&nbsp;Yupo Ma Ph.D. ,&nbsp;Weijia Wang Ph.D.","doi":"10.1016/j.jtct.2025.12.061","DOIUrl":"10.1016/j.jtct.2025.12.061","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Systemic lupus erythematosus (SLE) and lupus nephritis (LN) result from autoantibodies produced by CD19+ B cells and BCMA+ plasma cells. Autoimmune disease relapses after CD19 CAR-T successfully treated with subsequent plasma-cell-directed therapy suggests the need to target both cell types, in particular long-lived plasma cells. We report up to 67-month follow-up of ICG318 in SLE/LN being the first, to our knowledge, to show sustained stringent, medication-free, complete remission (CR) approaching 6 years.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;To provide updated long-term safety and efficacy of ICG318 to treat refractory SLE/LN in a phase I clinical trial.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Twelve patients (P) with refractory SLE, including 10 with biopsy-confirmed LN, were enrolled. P3-13 (excluding P11) received 3×10&lt;sup&gt;6&lt;/sup&gt; autologous ICG318 cells/kg following non-fludarabine conditioning with single-agent cyclophosphamide (0.3 g/m&lt;sup&gt;2&lt;/sup&gt;). Efficacy was assessed by stringent SLE CR criteria (sCR) requiring medication-free DORIS remission, complete renal response (CRR) and complete serological absence of disease. Endpoints included safety, serologies, medication use, B cell counts, immunoglobulin (IgG, IgM, IgA) and complement levels, and long-term clinical outcomes. Nine patients had follow-up renal biopsies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The median follow-up was 30 months (range, 19 to 67). Ten of 12 patients achieved enduring, sCR with no severe adverse events, infections attributed to ICG318, immune effector cell associated neurotoxicity syndrome, or cytokine release syndrome (CRS) above grade 1. All CRS events resolved with supportive care. Throughout follow-up, normalization of humoral cell counts, immunoglobulin and complement levels, and absence of all 9 autoantibodies examined was sustained in all patients, except P13. Eleven of 12 patients remained in durable DORIS remission with mean SLEDAI-2K scores decreasing from 9.5 at baseline to approximately 0.67 at the last follow-up. CRR was achieved in 9/10 LN patients. Repeat renal biopsies showed marked improvement with reductions in active inflammatory lesions in all 9 patients. P9 had 2 successful pregnancies post-ICG318, suggesting the therapy does not compromise female fertility.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In this landmark long-term follow-up, ICG318 exhibited remarkable safety and efficacy achieving durable sCR in 10 of 12 patients and reconstituted humoral immunity in all patients. Despite serological absence of disease, P6 failed to satisfy DORIS remission and CRR criteria due to persistent proteinuria from chronic, not active, renal disease evidenced by no IgG complexes on biopsy. Thus, 11 of 12 patients achieved medication-free serological remission. These findings support targeting both CD19 and BCMA in SLE/LN to achieve long-term sCR. With P1 sCR approaching 6 years, this may offer a first glimpse into the curativ","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S38"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098752","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":"Situational Awareness: The Development of a Bone Marrow Transplant Watcher Criteria","authors":"Connie Koons BSN, RN, BMTCN ,&nbsp;Alisha Drozd MSN, RNIV, BMTCN ,&nbsp;Shannon Sarver MSN, RN, RNC-NIC, NE-BC ,&nbsp;Juliann Theile BSN, RNIII, BMTCN ,&nbsp;Steffani Maier DNP, APRN, FNP-C, BMTCN","doi":"10.1016/j.jtct.2025.12.117","DOIUrl":"10.1016/j.jtct.2025.12.117","url":null,"abstract":"<div><h3>Topic Significance &amp; Study Purpose/Background/Rationale</h3><div>Pediatric bone marrow transplant (BMT) patients are vulnerable to rapid clinical deterioration due to their immunocompromised status. Identifying potential issues, timely recognition of symptoms, and escalation of care are critical. Situation awareness (SA) interventions were implemented house-wide to improve early recognition. Building from this work, BMT's quality improvement project tailored interventions aimed at having the right care provided at the right time and in the right place.</div></div><div><h3>Methods, Intervention, &amp; Analysis</h3><div>To improve the identification of “Watcher” patients, a multidisciplinary team on BMT reviewed clinical deterioration patterns of BMT patients and developed automatic Watcher criteria. Formal education was conducted with providers and nurses to ensure all were on the same page. SA huddles used a standardized checklist to align team understanding of the mental model and promote psychological safety. Watcher status was documented in EPIC, with visual cues and escalation criteria. A change from Pediatric Advanced Life Support (PALS) to Pediatric Emergency Management Simulation (PEMS) training for nurses was made to better support early recognition and escalation rather than code management. Simulations and in-situs were held on the unit to increase SA awareness and team cohesion.</div></div><div><h3>Findings &amp; Interpretation</h3><div>In FY25, the BMT team successfully identified patients and designated them as watchers at least one hour prior to ICU transfer in 60% of cases per 1,000 patient days—surpassing the house-wide rate of 48.6%. This achievement reflects the effectiveness of established criteria in promoting timely recognition and escalation of care with a vulnerable population.</div></div><div><h3>Discussion &amp; Implications</h3><div>Tailored criteria, team education, and simulation-based training foster a proactive safety culture. Simulations and in-situs have fostered stronger multidisciplinary collaboration and heightened SA across the unit. Embedding SA into BMT workflows enhances early recognition and escalation of care. Enabling earlier intervention both on the unit and within the first hour of ICU admission allows us to provide the right care, at the right time, in the right place</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S83"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098825","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":"Comprehensive Benchmarking of Outcomes after Anakinra Treatment for Refractory Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)","authors":"Smith Kungwankiattichai MD ,&nbsp;Emily C. Liang MD ,&nbsp;Xiancheng Wu MD ,&nbsp;Jenna M Voutsinas MSc ,&nbsp;Dwight C Macero MS, PA-C ,&nbsp;Yein Jeon MS ,&nbsp;Yang Qiao MS ,&nbsp;Jennifer J. Huang MD, PhD ,&nbsp;Andrew J. Portuguese MD ,&nbsp;Erik L. Kimble MD ,&nbsp;Alexandre V. Hirayama MD ,&nbsp;Mazyar Shadman MD, MPH ,&nbsp;Andy Chen MD, PhD ,&nbsp;Amrita Desai MD ,&nbsp;Brandon Hayes-Lattin MD ,&nbsp;Gabrielle Meyers MD ,&nbsp;Sanjog Bastola MD ,&nbsp;Manoj Rai MD ,&nbsp;Jessica T. Leonard MD ,&nbsp;Jacqueline Trussell MS ,&nbsp;Jordan Gauthier MD, MSc","doi":"10.1016/j.jtct.2025.12.029","DOIUrl":"10.1016/j.jtct.2025.12.029","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;ICANS remains a major cause of morbidity in CAR T-cell therapy recipients. Although early reports suggested safety of anakinra to treat severe or dexamethasone (dex)-refractory ICANS, outcomes in this patient population have not been characterized to date. To address this, we retrospectively analyzed a large cohort of patients (pts) uniformly treated with anakinra for severe and/or dex-refractory ICANS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We retrospectively analyzed 101 adults treated with CAR T-cell therapy at Fred Hutch Cancer Center (FHCC; n=64) and Oregon Health &amp; Science University (OHSU; n=37) between 2017-2025 receiving anakinra 200-300 mg intravenously every 8 hours for severe or dex-refractory ICANS. A significant neurologic improvement (SNI) was defined as a ≥2-grade improvement in ICANS from anakinra initiation in the absence of additional ICANS-directed therapy. ICANS-related treatment failure-free survival (TFFS) from anakinra initiation was defined as the probability of remaining free from subsequent ICANS-directed therapy, with patients censored at death.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The most common diseases were large B-cell lymphoma (49%), mantle cell lymphoma (22%), and acute lymphoblastic leukemia (12%). Grade ≥3 ICANS occurred in 82% of pts. Anakinra was initiated at a median of 1 day after ICANS onset, including after dex failure in 89 pts (88%).&lt;/div&gt;&lt;div&gt;We observed SNI at 24, 48, and 72 hours after anakinra initiation in 15%, 29%, and 42% of pts, respectively (Figure 1). The 28-day cumulative incidence of ICANS resolution was 86% (95% CI, 78–92%), with a median time to resolution of 8 days after anakinra initiation (Figure 2A). The 14-day ICANS-related TFFS after anakinra initiation was 74.8% (95% CI, 66.7-83.8) (Figure 2B). Twenty-six pts (26%) required additional therapies after anakinra initiation, including methylprednisolone (n = 21), intrathecal chemotherapy (n = 9), siltuximab (n = 2), and cetuximab (n = 1).&lt;/div&gt;&lt;div&gt;Next, we evaluated factors associated with outcomes. Older age (OR 0.96, 95% CI 0.92–0.99; p=0.014) and multiple myeloma (OR 0.08, 95% CI 0.001–0.69; p=0.016) were associated with lower odds of 48-hour SNI. Elevated day +0 lactate dehydrogenase (HR 0.34 per log10 U/L, 95% CI, 0.15–0.78; p=0.011) and ferritin (HR 0.67 per log10 ng/mL, 95% CI, 0.49–0.91; p=0.010) were associated with longer time to ICANS resolution. In multivariable analysis adjusting for CAR T-cell product type and day 0 ferritin, longer time to anakinra initiation from ICANS onset was independently associated with inferior TFFS (HR 1.16 per day, 95% CI, 1.01–1.34; p=0.042).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;In this large multicenter cohort, we benchmarked key outcomes in pts treated with anakinra for severe/dex-refractory ICANS: SNI at 72 hours, 42%; median time to ICANS resolution, 8 days; 14-day TFFS, 75%. Time to anakinra initiation independently impacted TFFS. Collectively, our find","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S13-S14"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098882","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":"Impact of Severe Infections on Non-Relapse Mortality after Allogeneic HCT: A Post-Hoc Analysis of a Randomized Phase II Study Comparing Post-Transplantation Cyclophosphamide (PTCy) and Non-Ptcy-Based GVHD Prophylaxis","authors":"Yehseo Jung B.A. ,&nbsp;Jeni Jensen M.D. ,&nbsp;Xinyi Fan MS ,&nbsp;Ted A. Gooley PhD ,&nbsp;Joshua A. Hill MD ,&nbsp;Prof. Brenda M. Sandmaier MD ,&nbsp;Masumi Ueda Oshima MD","doi":"10.1016/j.jtct.2025.12.107","DOIUrl":"10.1016/j.jtct.2025.12.107","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;A prior randomized phase II trial (NCT03246906) of graft-vs-host disease (GVHD) prophylaxis with sirolimus and cyclosporine combined with either post-transplant cyclophosphamide (PTCy) or mycophenolate mofetil (non-PTCy) showed superior GVHD-free relapse-free survival but delayed engraftment and higher rates of grade ≥3 infections with PTCy (Ueda Oshima, JCO 2025). However, there was no difference in non-relapse mortality (NRM).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To characterize the impact of infectious complications on NRM after PTCy and non-PTCy based GVHD prophylaxis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We retrospectively evaluated all infections by CTCAE version 4.03 and by BMT CTN Infection Grading System occurring in the 1st year post-HCT in patients treated on trial. Infections were assessed as time-varying covariates, with events censored at relapse. Cox regression assessed associations between severe infection and NRM and adjusted for age, conditioning, donor HLA-match, disease risk index, and HCT-CI.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among 145 patients, 441 total infections were recorded in the 1-year post-HCT. The estimated probability of 1-year NRM was PTCy 10% (95% CI 4-18%) vs. non-PTCy 7% (95% CI 3-14%). Among all patients, the cause-specific hazards of NRM among patients who developed an infection of any type by CTCAE grade ≥3 and BMT-CTN grade ≥2 compared to those who did not was 2.36 (95% CI, 1.01-5.52) and 1.38 (95% CI, 0.56-3.43), respectively (Table 1). Given the higher risk of infections observed with PTCy, we tested for any interaction by GVHD prophylaxis arm. Interestingly, the magnitude of impact of a CTCAE grade ≥3 and BMT CTN grade ≥2 infection on NRM varied by prophylaxis arm (Table 1; interaction p-value 0.12 and 0.33 for CTCAE and BMT CTN, respectively).&lt;/div&gt;&lt;div&gt;When considering specific infection type, bacterial infections CTCAE grade ≥3 and BMT CTN ≥2 showed a trend toward association with increased NRM, with a more detrimental effect in the PTCy group for CTCAE ≥3 infections (Table 1). For viral infections, the magnitudes of the detrimental effect on NRM were closer to 1.0, and the differential impact based on GVHD prophylaxis were not as marked. In the PTCy group, fungal infection by CTCAE or BMT CTN criteria were highly associated with NRM; there were no NRM events in the non-PTCy group (Table 1). Adjustment for patient and HCT factors individually did not change the overall pattern of findings. NRM causes are summarized in Table 2.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Severe infections were associated with markedly higher NRM in PTCy but not in non-PTCy patients. This differential effect was largely driven by bacterial and fungal infections and may be due to compromised immune reconstitution, delayed engraftment, and increased susceptibility to organ dysfunction after PTCy. Our findings suggest a need to optimize targeted infection surveillance, prevention and supportiv","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S72"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098474","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 First-in-Human Study of HLA-Partially to Fully Matched Allogeneic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients with Hematologic Malignancies","authors":"Sagar Munjal MD ,&nbsp;Sagar Patel MD ,&nbsp;Shahbaz Malik MD ,&nbsp;Uttam Rao MD, MBA ,&nbsp;Taiga Nishihori MD ,&nbsp;Preethi Prasad MS ,&nbsp;Vicki L Graves MS ,&nbsp;W Scott Goebel MD, PhD ,&nbsp;Erik J. Woods PhD","doi":"10.1016/j.jtct.2025.12.957","DOIUrl":"10.1016/j.jtct.2025.12.957","url":null,"abstract":"<div><h3>Background</h3><div>Cryopreserved bone marrow hematopoietic progenitor cells (HPCs) can serve as valuable option to address unmet needs in allogeneic hematopoietic cell transplants (HCT). PRESERVE I (NCT05589896) evaluates cryopreserved, minimally manipulated allogeneic HPCs from deceased donor vertebral body bone marrow (BM) across 4/8–8/8 HLA-matched grafts. These cells are processed using minimal manipulation. This report provides prespecified interim data for Cohort 1 (n=4).</div></div><div><h3>Methods</h3><div>Four hematologic malignancy patients received donor HPC, marrow. Transplants were performed using 4/8 HLA-matched grafts for patient 1, 3 &amp; 4, and 5/8 HLA-matched for patient 2. CD34+ cell doses were 5.72, 6.11, 5.22, and 7.53 × 10⁶ cells/kg, respectively. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus, mycophenolate mofetil (MMF), and post-transplant cyclophosphamide (50 mg/kg on Days +3 and +4). Neutrophil and platelet engraftment times were recorded; safety and GVHD were monitored; relapse and death were tracked.</div></div><div><h3>Results</h3><div>Patient 1 (age 52, T cell ALL) and patient 2 (age 62, AML) received myeloablative conditioning (MAC) while patient 3 (age 47, HTLV- ATLL) received reduced-intensity conditioning (RIC). Patient 4 (age 58, MDS) received RIC regimen.</div><div>Neutrophil engraftment was observed on Days +15, +17, +17 and +17; platelet engraftment observed on Days +18, +28, +20, and +27, respectively for the four patients. No clinically significant local toxicity reported on day of infusion Grade 1 skin acute GVHD manageable with steroids was reported for patient 4 on day 49 and resolved on day 52. No grade III-IV acute GVHD, or severe chronic GVHD, relapse, or death have been reported at the time of initial analysis. Mild chronic GVHD reported in patient 2 manifested by thrombocytopenia, peripheral edema and dysphagia, the patient was managed by methyl prednisone with resolution of symptoms. Secondary graft failure was reported for patient 3 after viral reactivation which was considered not related to the HPC marrow graft. No patient in cohort 1 met prespecified stopping rules.</div></div><div><h3>Conclusions</h3><div>These preliminary encouraging data from cohort 1 demonstrate that transplantation of the cryopreserved off the shelf HPC, marrow cells from deceased donors is feasible and safe for infusion. The interim cohort 1 data highlights the potential of this novel graft source for patients with unmet medical needs. Cohort 2 will proceed per the protocol to further evaluate safety and early efficacy.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S77-S78"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098509","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":"Tumor Microenvironment Archetyping from Cell-Free RNA in Plasma to Predict the Success of CAR T Therapy in Large B cell Lymphoma","authors":"Conor Loy PhD ,&nbsp;Glory Agun BS ,&nbsp;Caron A. Jacobson MD, MMSc ,&nbsp;Jerome Ritz MD ,&nbsp;Iwijn De Vlaminck PhD","doi":"10.1016/j.jtct.2025.12.075","DOIUrl":"10.1016/j.jtct.2025.12.075","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has transformed treatment for patients with relapsed or refractory large B-cell lymphoma (LBCL). However, many patients relapse or fail to achieve durable remission and there is an acute need for biomarkers that can predict response. Prior studies have reported that the composition of the tumor microenvironment (TME) is predictive of treatment response, and identified three main archetypes: lymph node (LN), follicular macrophage and accessory cell (FMAC), and T cell-exhausted (TEX) (Li et al., 2025). Importantly, LN-like environments were associated with superior responses. Yet, the reliance on invasive biopsies limits the feasibility of TME profiling in routine care. Cell-free RNA (cfRNA), RNA transcripts in blood plasma released by dying and activated cells, offers a compelling analyte to explore predictive signatures.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objectives&lt;/h3&gt;&lt;div&gt;To determine whether plasma cell-free RNA (cfRNA) can predict response to anti-CD19 CAR T cell therapy in patients with LBCL and to identify the cellular origin of prognostic transcripts.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We analyzed pre-treatment plasma cfRNA from 96 patients receiving axicabtagene ciloleucel (axi-cel) across three independent cohorts at the Dana Farber Cancer Institute. Responders were defined as patients with partial or complete response as measured by a PET-scan at one year post infusion. Samples were collected prior to leukapheresis or lymphodepletion and sequenced to an average of 33 million reads. Features predictive of response were discovered using Cohort 1 and validated across the remaining two independent cohorts. Single-cell RNA-seq (scRNA-seq) datasets from peripheral blood mononuclear cells (PBMCs) and TME biopsies were used to infer the cellular origin of cfRNA signals.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;cfRNA profiles captured pre-treatment signatures predictive of CAR T response. Lymphotoxin-beta (&lt;em&gt;LTB&lt;/em&gt;) emerged as the strongest predictor of treatment response in Cohort 1, and was elevated in responders across all three cohorts. Integration with scRNA-seq data demonstrated that LTB expression was enriched within the TME of responders, but not in PBMCs, indicating cfRNA includes signatures of the TME. Gene module scoring revealed that cfRNA captured signatures of the LN-archetype which was associated with favorable response. Predictive modeling using LN-archetype marker genes achieved the highest classification performance across train/test iterations, supporting the translational relevance of cfRNA-derived TME signals.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Pre-treatment plasma cfRNA reflects the TME in LBCL and can predict response to anti-CD19 CAR T cell therapy. cfRNA-based profiling enables non-invasive assessment of TME status from blood, offering a scalable liquid biopsy approach for patient stratification and future companion diagnostic development.&lt;/","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S48"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098748","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}