Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.10.017
Marta Peña , Diego Fernando Martinez , Lucía López-Corral , Ana África Martín-López , Mario Sanchez-Salinas , Ana Benzaquén , Rafael Hernani , Jaime Sanz , Aitana Balaguer , Mar Perera , Anna Torrent , Antonio Pérez-Martínez , Silvia Filaferro , Pascual Balsalobre , Pere Barba , Alberto Mussetti
The Endothelial Activation and Stress Index (EASIX) has been proposed as a predictor of endothelial complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients undergoing chimeric antigen receptor (CAR) T-cell therapy. However, its prognostic role for long-term survival after commercial anti-CD19 CAR T-cell therapy remains uncertain. To evaluate the prognostic value of EASIX in predicting survival outcomes and toxicity in patients treated with CAR T-cell therapy, and to compare its performance with commonly available clinical biomarkers. This retrospective multicenter study included 126 patients with aggressive B-cell lymphomas treated with commercially available CAR T-cell products across multiple centers in Spain. EASIX-d0 was calculated prior to CAR-T infusion (EASIX-d0). Cox proportional hazards models assessed associations with overall survival (OS) and progression-free survival (PFS), while logistic regression was used for toxicity outcomes. Receiver operating characteristic (ROC) analysis compared the predictive performance of EASIX-d0 versus LDH. A combined LDH-ECOG PS status risk model was also evaluated. Higher EASIX-d0 values were associated with inferior OS (HR: 1.52, P < .001) and PFS (HR: 1.30, P < .001). Patients in the highest EASIX-d0 quartile showed significantly worse OS (HR: 4.40, P = .002) and PFS (HR: 2.50, P = .03). However, predictive performance did not differ between EASIX-d0 and LDH alone for OS (AUC 71.6% vs 71.3%, P = .935) or PFS (68.5% vs 66.6%, P = .618). A combined LDH-ECOG model identified 3 risk groups with superior discrimination of OS and PFS compared to EASIX-d0. EASIX-d0 was associated with ICANS grades 2 to 4 and 3 to 4 (OR 1.66, P = .001; OR 2.10, P = .001), but showed no association with CRS or nonrelapse mortality. While EASIX-d0 predicts survival and ICANS in CAR T-cell recipients, however its predictive capacity was largely driven by LDH. it does not outperform more accessible markers such as LDH and ECOG PS. While recent studies suggested associations between EASIX and overall survival, our results highlight that simpler parameters such as LDH and ECOG Performance Status may provide equal or superior predictive power in real-world cohorts.
内皮活化和应激指数（EASIX）已被提出作为内皮并发症的预测指标，如细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）在接受嵌合抗原受体（CAR） t细胞治疗的患者中。然而，它在商业抗cd19 CAR -t细胞治疗后的长期生存中的预后作用仍然不确定。评估EASIX在预测CAR - t细胞治疗患者的生存结果和毒性方面的预后价值，并将其性能与常用的临床生物标志物进行比较。这项回顾性多中心研究包括西班牙多个中心126例侵袭性b细胞淋巴瘤患者，这些患者接受市售CAR - t细胞产品治疗。CAR-T输注前计算EASIX-d0 （EASIX-d0）。Cox比例风险模型评估了总生存期（OS）和无进展生存期（PFS）的相关性，而毒性结果则使用逻辑回归。受试者工作特征（ROC）分析比较EASIX-d0与LDH的预测性能。并对LDH-ECOG - PS状态风险模型进行了评价。较高的EASIX-d0值与较差的OS （HR: 1.52, P < .001）和PFS （HR: 1.30, P < .001）相关。EASIX-d0四分位数最高的患者OS较差（HR: 4.40, P = ）。002)和PFS （HR: 2.50, P = .03）。然而，EASIX-d0和单独使用LDH对OS的预测性能没有差异（AUC为71.6% vs 71.3%, P = ）。935)或PFS （68.5% vs 66.6%, P = .618）。LDH-ECOG联合模型识别出3个风险组，与EASIX-d0相比，OS和PFS的区分能力更强。EASIX-d0与ICANS 2 ~ 4级和3 ~ 4级相关（OR 1.66, P = .001;OR 2.10, P = ）。001)，但与CRS或非复发死亡率无关。虽然easix - 0预测CAR - t细胞受体的生存和ICANS，但其预测能力主要由LDH驱动。虽然最近的研究表明EASIX与总生存率之间存在关联，但我们的研究结果强调，LDH和ECOG性能状态等更简单的参数可能在现实世界的队列中提供同等或更好的预测能力。
{"title":"EASIX Does Not Add Prognostic Value Beyond Lactate Dehydrogenase and ECOG Performance Status in CAR T-Cell Therapy: A GETH-TC Study","authors":"Marta Peña , Diego Fernando Martinez , Lucía López-Corral , Ana África Martín-López , Mario Sanchez-Salinas , Ana Benzaquén , Rafael Hernani , Jaime Sanz , Aitana Balaguer , Mar Perera , Anna Torrent , Antonio Pérez-Martínez , Silvia Filaferro , Pascual Balsalobre , Pere Barba , Alberto Mussetti","doi":"10.1016/j.jtct.2025.10.017","DOIUrl":"10.1016/j.jtct.2025.10.017","url":null,"abstract":"<div><div>The Endothelial Activation and Stress Index (EASIX) has been proposed as a predictor of endothelial complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients undergoing chimeric antigen receptor (CAR) T-cell therapy. However, its prognostic role for long-term survival after commercial anti-CD19 CAR T-cell therapy remains uncertain. To evaluate the prognostic value of EASIX in predicting survival outcomes and toxicity in patients treated with CAR T-cell therapy, and to compare its performance with commonly available clinical biomarkers. This retrospective multicenter study included 126 patients with aggressive B-cell lymphomas treated with commercially available CAR T-cell products across multiple centers in Spain. EASIX-d0 was calculated prior to CAR-T infusion (EASIX-d0). Cox proportional hazards models assessed associations with overall survival (OS) and progression-free survival (PFS), while logistic regression was used for toxicity outcomes. Receiver operating characteristic (ROC) analysis compared the predictive performance of EASIX-d0 versus LDH. A combined LDH-ECOG PS status risk model was also evaluated. Higher EASIX-d0 values were associated with inferior OS (HR: 1.52, <em>P</em> < .001) and PFS (HR: 1.30, <em>P</em> < .001). Patients in the highest EASIX-d0 quartile showed significantly worse OS (HR: 4.40, <em>P</em> = .002) and PFS (HR: 2.50, <em>P</em> = .03). However, predictive performance did not differ between EASIX-d0 and LDH alone for OS (AUC 71.6% vs 71.3%, <em>P</em> = .935) or PFS (68.5% vs 66.6%, <em>P</em> = .618). A combined LDH-ECOG model identified 3 risk groups with superior discrimination of OS and PFS compared to EASIX-d0. EASIX-d0 was associated with ICANS grades 2 to 4 and 3 to 4 (OR 1.66, <em>P</em> = .001; OR 2.10, <em>P</em> = .001), but showed no association with CRS or nonrelapse mortality. While EASIX-d0 predicts survival and ICANS in CAR T-cell recipients, however its predictive capacity was largely driven by LDH. it does not outperform more accessible markers such as LDH and ECOG PS. While recent studies suggested associations between EASIX and overall survival, our results highlight that simpler parameters such as LDH and ECOG Performance Status may provide equal or superior predictive power in real-world cohorts.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 169.e1-169.e10"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514243","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.2025.10.032
Ilias Christodoulou , Kristine Cooper , Valerie Gao , Ashley McFarquhar , Kathleen Dorritie , Warren D. Shlomchik
Patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) undergoing chimeric antigen receptor T cell therapy targeting CD19 (CART-19) receive preinfusion lymphodepletion (LD), most commonly with fludarabine/cyclophosphamide (flu/cy). During the fludarabine shortage, bendamustine was used as an alternative. There are only limited data on how outcomes with flu/cy and bendamustine LD compare. We aimed to compare outcomes and toxicity profiles in r/r DLBCL patients lymphodepleted with flu/cy or bendamustine prior to CART-19 therapy.We conducted a retrospective single-center study comparing DLBCL patients who received axicabtagene ciloleucel (axi-cel; 74.4%) or lisocabtagene maraleucel (liso-cel; 25.6%) following flu/cy or bendamustine LD. A propensity score-matched data set was created to balance baseline covariates between the LD groups (45 patients per LD group). Covariates addressed included age, stage, bridging therapy, number of prior therapies, CART-19 product, and pre-LD C-reactive protein (CRP) and lactate dehydrogenase (LDH). Outcomes, including response rates, overall survival (OS), progression-free survival (PFS), cytokine release syndrome (CRS), immune effector cell neurotoxicity syndrome (ICANS), and hematologic toxicities, were evaluated.The 3-month overall and complete response rates (ORR; CR) were similar in the flu/cy (64.4% and 60%) and bendamustine groups (64.4% and 51.1%; ORR: P = 1; CR: P = .40). At 6 months, no differences in PFS (flu/cy 62.2% vs bendamustine 58.2%; P = .37) or OS (flu/cy 86.7% vs bendamustine 79.9%; P = .83) were noted. Incidences of CRS and ICANS were comparable in the flu/cy (CRS, 79.1%; ICANS, 42.2%) and bendamustine cohorts (CRS, 71.1%; ICANS 28.9%; all P > .05). However, the median time to peak CRS (3 vs 5 days; P = .002) and ICANS (6 vs 9 days; P = .034) occurred earlier in the flu/cy cohort. The flu/cy cohort also had lower median absolute neutrophil, platelet and hemoglobin nadirs (all P ≤ .001). Moreover, flu/cy was associated with higher rates of severe (G ≥ 3) neutropenia (100% vs 73%; P < .001), anemia (54.5% vs 24.4%; P = .012), and thrombocytopenia (57.5% vs 29.7%; P = .019). Within the limitations of the size of our study and its retrospective nature, flu/cy and bendamustine LD resulted in similar ORR, PFS and OS; however, bendamustine had less hematologic toxicity. Bendamustine can be a viable alternative LD agent for CART-19 therapy for DLBCL, especially in patients with a compromised performance status.
{"title":"Comparative Analysis of Lymphodepletion Regimens in CART-19 Treatment for Relapsed/Refractory Diffuse Large B Cell Lymphoma","authors":"Ilias Christodoulou , Kristine Cooper , Valerie Gao , Ashley McFarquhar , Kathleen Dorritie , Warren D. Shlomchik","doi":"10.1016/j.jtct.2025.10.032","DOIUrl":"10.1016/j.jtct.2025.10.032","url":null,"abstract":"<div><div>Patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) undergoing <u>c</u>himeric <u>a</u>ntigen <u>r</u>eceptor <u>T</u> cell therapy targeting CD<u>19</u> (CART-19) receive preinfusion lymphodepletion (LD), most commonly with fludarabine/cyclophosphamide (flu/cy). During the fludarabine shortage, bendamustine was used as an alternative. There are only limited data on how outcomes with flu/cy and bendamustine LD compare. We aimed to compare outcomes and toxicity profiles in r/r DLBCL patients lymphodepleted with flu/cy or bendamustine prior to CART-19 therapy.We conducted a retrospective single-center study comparing DLBCL patients who received axicabtagene ciloleucel (axi-cel; 74.4%) or lisocabtagene maraleucel (liso-cel; 25.6%) following flu/cy or bendamustine LD. A propensity score-matched data set was created to balance baseline covariates between the LD groups (45 patients per LD group). Covariates addressed included age, stage, bridging therapy, number of prior therapies, CART-19 product, and pre-LD C-reactive protein (CRP) and lactate dehydrogenase (LDH). Outcomes, including response rates, overall survival (OS), progression-free survival (PFS), cytokine release syndrome (CRS), immune effector cell neurotoxicity syndrome (ICANS), and hematologic toxicities, were evaluated.The 3-month overall and complete response rates (ORR; CR) were similar in the flu/cy (64.4% and 60%) and bendamustine groups (64.4% and 51.1%; ORR: <em>P =</em> 1; CR: <em>P =</em> .40). At 6 months, no differences in PFS (flu/cy 62.2% vs bendamustine 58.2%; <em>P</em> = .37) or OS (flu/cy 86.7% vs bendamustine 79.9%; <em>P</em> = .83) were noted. Incidences of CRS and ICANS were comparable in the flu/cy (CRS, 79.1%; ICANS, 42.2%) and bendamustine cohorts (CRS, 71.1%; ICANS 28.9%; all <em>P</em> > .05). However, the median time to peak CRS (3 vs 5 days; <em>P</em> = .002) and ICANS (6 vs 9 days; <em>P</em> = .034) occurred earlier in the flu/cy cohort. The flu/cy cohort also had lower median absolute neutrophil, platelet and hemoglobin nadirs (all <em>P</em> ≤ .001). Moreover, flu/cy was associated with higher rates of severe (G ≥ 3) neutropenia (100% vs 73%; <em>P</em> < .001), anemia (54.5% vs 24.4%; <em>P</em> = .012), and thrombocytopenia (57.5% vs 29.7%; <em>P</em> = .019). Within the limitations of the size of our study and its retrospective nature, flu/cy and bendamustine LD resulted in similar ORR, PFS and OS; however, bendamustine had less hematologic toxicity. Bendamustine can be a viable alternative LD agent for CART-19 therapy for DLBCL, especially in patients with a compromised performance status.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages 173.e1-173.e11"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2026.01.034
Juan Montoro, Aitana Balaguer-Roselló, Pedro Chorao, Pablo Granados, Pedro Asensi, Marta Villalba, Pilar Solves, Inés Gómez-Segui, Javier de la Rubia, Miguel A Sanz, Jaime Sanz
{"title":"Bone marrow transplantation from matched and mismatched unrelated donors with post-transplant cyclophosphamide for patients with severe aplastic anemia.","authors":"Juan Montoro, Aitana Balaguer-Roselló, Pedro Chorao, Pablo Granados, Pedro Asensi, Marta Villalba, Pilar Solves, Inés Gómez-Segui, Javier de la Rubia, Miguel A Sanz, Jaime Sanz","doi":"10.1016/j.jtct.2026.01.034","DOIUrl":"https://doi.org/10.1016/j.jtct.2026.01.034","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114360","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.2025.12.038
Christopher McKinney MD , Hemalatha G Rangarajan MD , Leyla Shune MD , Ashley N. Gray M.D., M.S. , Haydar Frangoul MD, MS , Jonathan D Fish MD , Claudia Pagan MPH , Sonali Chaudhury MD, MBBS
<div><h3>Introduction</h3><div>Commercially available gene therapies expand the potential curative therapies for individuals with SCD and TDT. Collection and manufacturing of an adequate number of CD34 cells is essential for the patients to undergo this therapy. Challenges remain due to limitations related to stem cell mobilization, apheresis collection efficiency, and losses during manufacturing process.</div></div><div><h3>Methods</h3><div>ReGenT, a forum for strategic planning and data sharing across 45+ gene therapy centers, aims to establish harmonized approaches and study real world outcomes. To date around 100 patients with SCD and TDT have consented to receive autologous genetically modified commercial CD34+ HSC drug product (minimum FDA approved dose 3 and 5 X 10^6 CD34 for SCD and TDT respectively).</div></div><div><h3>Results</h3><div>We report on post standard mobilization cell collection and product manufacture process in 33 patients (15 SCD and 18 TDT) from 5 centers, as additional data collection is ongoing. SCD received plerixafor mobilization while TDT received a combination of plerixafor and G-CSF. Two SCD patients received motixafortide.</div><div>Time from consent to mobilization was an average of 3 months with no difference between TDT/SCD. All SCD patients receiving 3-5 months of preceding chronic transfusions with pre collection HbS% of 13 (0-22) and stopped HU > 3months prior to first collection reflecting adequate erythroid suppression. All patients collected via a central line.</div><div>For TDT (median age 13y), 66% patients needed 1 cycle (range 1-3) with average 3 days of collection with only 1patient needing 3 cycles. Median baseline CD 34 (pre plerixafor) was 22.5 (5-105)/ul and post plerixafor peak CD34 was 162 (73-517)/ul. Median cells sent for manufacturing 37.7 x 10^6 CD34/kg (20.8-94.7). Product was created for 90% TDT patients.</div><div>For SCD (median age 18y), 44 % patients collected in 1 cycle, 5 patients needed 2 cycles. Of the remaining 50% needed ≥ 3 cycles with 2 patients needing 5 cycles). Median CD 34 (pre and post plerixafor) was 11(<5 -69)/ul and 100(23-405)/uL respectively. Median cells sent for manufacturing were 19.8 X 10^6 CD34/kg (4.8-65).</div><div>Manufacturing failure was reported in 18% patients (2 TDT and 3 SCD) due to inability to meet release criteria. In addition, >50% SCD patients had inadequate drug product generated in 1 cycle due to low cell dose generated.</div></div><div><h3>Conclusion</h3><div>With ongoing data collection from the other centers, we demonstrate more significant challenges in mobilization, collection and manufacturing in the post-commercialization era as manufacturing scales nationally, compared to reports from the original clinical trial experience and the importance of need to improve manufacturing, increased apheresis days/cycle. Variability in CD34 + collection highlights the need for better predictive strategies to allow for optimal collection and al
商业上可用的基因疗法扩大了SCD和TDT患者的潜在治疗方法。收集和制造足够数量的CD34细胞对于患者接受这种治疗至关重要。由于干细胞动员、单采收集效率和制造过程中的损失等方面的限制，挑战仍然存在。regent是一个跨45多个基因治疗中心的战略规划和数据共享论坛，旨在建立统一的方法并研究现实世界的结果。迄今为止，约有100名SCD和TDT患者已同意接受自体转基因CD34+ HSC商业化药物（FDA批准的SCD和TDT的最低剂量分别为3和5 X 10^6 CD34）。我们报告了来自5个中心的33例患者（15例SCD和18例TDT）的标准后动员细胞收集和产品制造过程，其他数据收集正在进行中。SCD接受plerixafor动员，TDT接受plerixafor和G-CSF联合动员。2例SCD患者接受莫替福肽治疗。从同意到动员的平均时间为3个月，TDT/SCD之间没有差异。所有SCD患者在采集前接受3-5个月的慢性输血，HbS%为13(0-22)，并在首次采集前3个月停止输血，反映红细胞得到充分抑制。所有病人都通过中央静脉输送。对于TDT（中位年龄13y）， 66%的患者需要1个周期（范围1-3），平均3天收集，只有1例患者需要3个周期。中位基线CD34（注射前）为22.5 (5-105)/ul，注射后峰值CD34为162 (73-517)/ul。用于制造的中位数细胞37.7 x 10^6 CD34/kg（20.8-94.7）。产品是为90%的TDT患者创建的。对于SCD（中位年龄18岁），44%的患者1个周期收集，5例患者需要2个周期。其余50%需要≥3个周期（2例需要5个周期）。中位cd34（叠前和叠后）分别为11(5 -69)/ul和100(23-405)/ ul。用于制造的细胞中位数为19.8 X 10^6 CD34/kg（4.8-65）。18%的患者（2例TDT和3例SCD）由于无法满足释放标准而报告制造失败。此外，50%的SCD患者由于产生的细胞剂量低，导致1个周期内产生的药品不足。通过从其他中心持续收集的数据，我们发现，与最初的临床试验经验报告相比，随着生产规模在全国范围内扩大，后商业化时代在动员、收集和生产方面面临着更大的挑战，需要改进生产，增加采血天数/周期。CD34 + 收集的可变性强调需要更好的预测策略，以实现最佳收集，并允许交替动员和采血调整。
{"title":"Collection and Manufacture of Autologous HSC Gene Therapy Cell Product for Patients with Sickle Cell Disease (SCD) and Transfusion Dependent Thalassemia (TDT): A Real World Gene Therapy (ReGenT) Consortium Report.","authors":"Christopher McKinney MD , Hemalatha G Rangarajan MD , Leyla Shune MD , Ashley N. Gray M.D., M.S. , Haydar Frangoul MD, MS , Jonathan D Fish MD , Claudia Pagan MPH , Sonali Chaudhury MD, MBBS","doi":"10.1016/j.jtct.2025.12.038","DOIUrl":"10.1016/j.jtct.2025.12.038","url":null,"abstract":"<div><h3>Introduction</h3><div>Commercially available gene therapies expand the potential curative therapies for individuals with SCD and TDT. Collection and manufacturing of an adequate number of CD34 cells is essential for the patients to undergo this therapy. Challenges remain due to limitations related to stem cell mobilization, apheresis collection efficiency, and losses during manufacturing process.</div></div><div><h3>Methods</h3><div>ReGenT, a forum for strategic planning and data sharing across 45+ gene therapy centers, aims to establish harmonized approaches and study real world outcomes. To date around 100 patients with SCD and TDT have consented to receive autologous genetically modified commercial CD34+ HSC drug product (minimum FDA approved dose 3 and 5 X 10^6 CD34 for SCD and TDT respectively).</div></div><div><h3>Results</h3><div>We report on post standard mobilization cell collection and product manufacture process in 33 patients (15 SCD and 18 TDT) from 5 centers, as additional data collection is ongoing. SCD received plerixafor mobilization while TDT received a combination of plerixafor and G-CSF. Two SCD patients received motixafortide.</div><div>Time from consent to mobilization was an average of 3 months with no difference between TDT/SCD. All SCD patients receiving 3-5 months of preceding chronic transfusions with pre collection HbS% of 13 (0-22) and stopped HU > 3months prior to first collection reflecting adequate erythroid suppression. All patients collected via a central line.</div><div>For TDT (median age 13y), 66% patients needed 1 cycle (range 1-3) with average 3 days of collection with only 1patient needing 3 cycles. Median baseline CD 34 (pre plerixafor) was 22.5 (5-105)/ul and post plerixafor peak CD34 was 162 (73-517)/ul. Median cells sent for manufacturing 37.7 x 10^6 CD34/kg (20.8-94.7). Product was created for 90% TDT patients.</div><div>For SCD (median age 18y), 44 % patients collected in 1 cycle, 5 patients needed 2 cycles. Of the remaining 50% needed ≥ 3 cycles with 2 patients needing 5 cycles). Median CD 34 (pre and post plerixafor) was 11(<5 -69)/ul and 100(23-405)/uL respectively. Median cells sent for manufacturing were 19.8 X 10^6 CD34/kg (4.8-65).</div><div>Manufacturing failure was reported in 18% patients (2 TDT and 3 SCD) due to inability to meet release criteria. In addition, >50% SCD patients had inadequate drug product generated in 1 cycle due to low cell dose generated.</div></div><div><h3>Conclusion</h3><div>With ongoing data collection from the other centers, we demonstrate more significant challenges in mobilization, collection and manufacturing in the post-commercialization era as manufacturing scales nationally, compared to reports from the original clinical trial experience and the importance of need to improve manufacturing, increased apheresis days/cycle. Variability in CD34 + collection highlights the need for better predictive strategies to allow for optimal collection and al","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S21-S22"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098504","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}
Topic Significance & Study Purpose/Background/Rationale
Hematopoietic progenitor cells (HPC) are traditionally infused by gravity, although most blood products are administered via infusion pumps. Concerns about potential cellular damage from peristaltic mechanisms have restricted pump use, despite limited supporting evidence. Recent studies and institutional reports demonstrate equivalent engraftment outcomes between gravity and pump infusion, while pumps offer consistent flow rates, streamlined tubing setup, and reduced dimethyl sulfoxide (DMSO) exposure. For cellular therapy nurses, safe and efficient HPC delivery is critical to both patient outcomes and workflow optimization. This quality improvement initiative, in collaboration with the cell therapy lab, evaluated the safety and feasibility of transitioning HPC infusion from gravity to pump using a phased, evidence-based approach: risk assessment, pre-clinical validation, and clinical pilot.
Methods, Intervention, & Analysis
• Risk assessment: The Quality Management Committee reviewed evidence, identified risks, planned mitigation strategies, and approved validation and pilot phases.
• Pre-clinical validation: Six cryopreserved HPC products scheduled for discard (from 3 patients, 2 bags each) were thawed and transferred into new bags (1 bag per patient for each method). Pre- and post-infusion samples were analyzed for viable CD34+ cell percentage and dose recovery, and compared between infusion methods.
• Clinical pilot: Ten autologous HPC infusions were administered via pump and compared with institutional historical gravity infusion data for time to neutrophil and platelet engraftment, adverse events, and staff feedback.
Findings & Interpretation
Pre-clinical validation demonstrated equivalent or improved HPC integrity with pump infusion, showing up to 10.8% higher viable CD34+ percentage and 11% higher dose recovery compared with gravity.
In the clinical pilot, neutrophil and platelet engraftment times were consistent with historical gravity infusions. No clinically significant difference in adverse effects was associated with pump infusion. Nursing and lab staff reported improved efficiency, standardized tubing setup, and less manual flushing. Findings align with published evidence demonstrating pump infusion safety.
Discussion & Implications
Transitioning HPC infusion from gravity to pump is safe, preserves product integrity, enhances consistency, and improves workflow. A phased approach – risk assessment, laboratory validation, and monitored pilot – facilitated successful implementation while safeguarding patient safety. Broader adoption of pump infusion across cellular therapies may enhance safety, streamline processes, and exemplify the nursing role in driving evidence-based clinical innovation.
{"title":"Pumping up Safety and Efficiency: Modernizing Hematopoietic Stem Cell Infusion","authors":"Vivian Huang MS, RN, CNS, AGCNS-BC, BMTCN, OCN, Melanie McMillan BS, CLS","doi":"10.1016/j.jtct.2025.12.111","DOIUrl":"10.1016/j.jtct.2025.12.111","url":null,"abstract":"<div><h3>Topic Significance & Study Purpose/Background/Rationale</h3><div>Hematopoietic progenitor cells (HPC) are traditionally infused by gravity, although most blood products are administered via infusion pumps. Concerns about potential cellular damage from peristaltic mechanisms have restricted pump use, despite limited supporting evidence. Recent studies and institutional reports demonstrate equivalent engraftment outcomes between gravity and pump infusion, while pumps offer consistent flow rates, streamlined tubing setup, and reduced dimethyl sulfoxide (DMSO) exposure. For cellular therapy nurses, safe and efficient HPC delivery is critical to both patient outcomes and workflow optimization. This quality improvement initiative, in collaboration with the cell therapy lab, evaluated the safety and feasibility of transitioning HPC infusion from gravity to pump using a phased, evidence-based approach: risk assessment, pre-clinical validation, and clinical pilot.</div></div><div><h3>Methods, Intervention, & Analysis</h3><div>• Risk assessment: The Quality Management Committee reviewed evidence, identified risks, planned mitigation strategies, and approved validation and pilot phases.</div><div>• Pre-clinical validation: Six cryopreserved HPC products scheduled for discard (from 3 patients, 2 bags each) were thawed and transferred into new bags (1 bag per patient for each method). Pre- and post-infusion samples were analyzed for viable CD34+ cell percentage and dose recovery, and compared between infusion methods.</div><div>• Clinical pilot: Ten autologous HPC infusions were administered via pump and compared with institutional historical gravity infusion data for time to neutrophil and platelet engraftment, adverse events, and staff feedback.</div></div><div><h3>Findings & Interpretation</h3><div>Pre-clinical validation demonstrated equivalent or improved HPC integrity with pump infusion, showing up to 10.8% higher viable CD34+ percentage and 11% higher dose recovery compared with gravity.</div><div>In the clinical pilot, neutrophil and platelet engraftment times were consistent with historical gravity infusions. No clinically significant difference in adverse effects was associated with pump infusion. Nursing and lab staff reported improved efficiency, standardized tubing setup, and less manual flushing. Findings align with published evidence demonstrating pump infusion safety.</div></div><div><h3>Discussion & Implications</h3><div>Transitioning HPC infusion from gravity to pump is safe, preserves product integrity, enhances consistency, and improves workflow. A phased approach – risk assessment, laboratory validation, and monitored pilot – facilitated successful implementation while safeguarding patient safety. Broader adoption of pump infusion across cellular therapies may enhance safety, streamline processes, and exemplify the nursing role in driving evidence-based clinical innovation.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S80"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098511","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.2025.12.048
Yannis Valtis MD , Karamjeet S. Sandhu MD , Rawan Faramand MD , Amy Zhang MPH , Katharine Miller PhD , LaQuisa C. Hill MD , Ibrahim N. Muhsen MD , Tamer Othman MD , Marlise Luskin MD, MSCE , Evan C. Chen MD , Caspian Oliai MD, MS , Georgia Lill MD , Ryan D. Cassaday MD , Noam E. Kopmar MD , Aaron C Logan MD, PhD , Matthew P. Connor MD , Talal Hilal MD , Jae H Park MD , Melhem M Solh MD , Caitlin Guzowski MBA , Noelle V. Frey MD
<div><h3>Introduction</h3><div>Obecabtagene autoleucel (obe-cel) and brexucabtagene autoleucel (brexu-cel) are CD19 targeted chimeric antigen receptor T cell (CAR-T) therapies, approved for adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). Mechanistic differences between obe-cel and brexu-cel including differing costimulatory domains (4-1BB vs. CD28), CD19 binding domains (intermediate vs. high affinity) and split dose (Days 1 and 10) vs. single infusion may impact in-vivo cellular kinetics that translate into variant clinical outcomes. Real-world utilization and outcomes with obe-cel are unknown given the relatively recent approval.</div></div><div><h3>Methods</h3><div>The ROCCA database, comprising real world data from patients (pts) with r/r ALL treated at 40 North American institutions was used in this analysis. Pts with r/r ALL were eligible if they were apheresed for obe-cel since its approval (11/8/2024) or brexu-cel over a comparable period (since 8/1/24) and had at least 30 days of follow up. Data cut off was 7/15/2025. CRS/ICANS were graded per ASTCT criteria. Measurable residual disease (MRD) was assessed by flow cytometry and/or next generation sequencing per institutional standards.</div></div><div><h3>Results</h3><div>38 pts have undergone apheresis for obe-cel (36 infused, all received both infusions) and 54 (53 infused) for brexu-cel over the study period. Baseline characteristics are shown in Table 1.</div><div>CAR-mediated toxicity differed significantly between the cohorts (Table 2). CRS occurred in 56% of obe-cel pts compared to 94% of brexu-cel pts (p < 0.0001). There were no Gr3+ CRS events among the obe-cel pts; 3 (6%) brexu-cel pts had Gr3+ CRS (p = 0.27). ICANS occurred in 17% of obe-cel pts vs. 51% of brexu-cel pts (p = 0.001). Gr3+ ICANS occurred in 6% of obe-cel vs. 32% of brexu-cel pts (p = 0.0027). Among the obe-cel pts, CRS occurred in 31% after the first infusion and 46% after the second; ICANS occurred in 3% after the first infusion and 15% after the second. Prolonged Gr4 neutropenia (ANC < 500 cells/uL beyond day 30 from infusion) occurred in 24% of obe-cel vs. 28% of brexu-cel pts (p = 0.73). Deaths within the first 28 days of infusion occurred in 0 obe-cel pts and 4 brexu-cel pts (2 of infection, 1 of infection/brain bleed, and 1 of liver failure in the setting of Gr4 CRS and HLH).</div><div>Response rates were high and did not significantly differ between cohorts (p = 0.85) (Table 3). 81% of obe-cel pts vs. 80% of brexu-cel pts achieved an MRD- CR/CRi.</div></div><div><h3>Conclusion</h3><div>Pts selected for obe-cel apheresis were similar to those for brexu-cel over the study period (noting that not all centers had access to obe-cel during this time). Similar to clinical trial results, obe-cel was associated with lower rates of CRS/ICANS. Rates of MRD-negative CR were high and did not differ between cohorts. A larger sample and longer follow up are required for further anal
{"title":"Patient Characteristics, Toxicity, and Response after Real World Administration of Obecabtagene Autoleucel and Brexucabtagene Autoleucel for Relapsed Acute Lymphoblastic Leukemia: A Rocca Analysis","authors":"Yannis Valtis MD , Karamjeet S. Sandhu MD , Rawan Faramand MD , Amy Zhang MPH , Katharine Miller PhD , LaQuisa C. Hill MD , Ibrahim N. Muhsen MD , Tamer Othman MD , Marlise Luskin MD, MSCE , Evan C. Chen MD , Caspian Oliai MD, MS , Georgia Lill MD , Ryan D. Cassaday MD , Noam E. Kopmar MD , Aaron C Logan MD, PhD , Matthew P. Connor MD , Talal Hilal MD , Jae H Park MD , Melhem M Solh MD , Caitlin Guzowski MBA , Noelle V. Frey MD","doi":"10.1016/j.jtct.2025.12.048","DOIUrl":"10.1016/j.jtct.2025.12.048","url":null,"abstract":"<div><h3>Introduction</h3><div>Obecabtagene autoleucel (obe-cel) and brexucabtagene autoleucel (brexu-cel) are CD19 targeted chimeric antigen receptor T cell (CAR-T) therapies, approved for adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). Mechanistic differences between obe-cel and brexu-cel including differing costimulatory domains (4-1BB vs. CD28), CD19 binding domains (intermediate vs. high affinity) and split dose (Days 1 and 10) vs. single infusion may impact in-vivo cellular kinetics that translate into variant clinical outcomes. Real-world utilization and outcomes with obe-cel are unknown given the relatively recent approval.</div></div><div><h3>Methods</h3><div>The ROCCA database, comprising real world data from patients (pts) with r/r ALL treated at 40 North American institutions was used in this analysis. Pts with r/r ALL were eligible if they were apheresed for obe-cel since its approval (11/8/2024) or brexu-cel over a comparable period (since 8/1/24) and had at least 30 days of follow up. Data cut off was 7/15/2025. CRS/ICANS were graded per ASTCT criteria. Measurable residual disease (MRD) was assessed by flow cytometry and/or next generation sequencing per institutional standards.</div></div><div><h3>Results</h3><div>38 pts have undergone apheresis for obe-cel (36 infused, all received both infusions) and 54 (53 infused) for brexu-cel over the study period. Baseline characteristics are shown in Table 1.</div><div>CAR-mediated toxicity differed significantly between the cohorts (Table 2). CRS occurred in 56% of obe-cel pts compared to 94% of brexu-cel pts (p < 0.0001). There were no Gr3+ CRS events among the obe-cel pts; 3 (6%) brexu-cel pts had Gr3+ CRS (p = 0.27). ICANS occurred in 17% of obe-cel pts vs. 51% of brexu-cel pts (p = 0.001). Gr3+ ICANS occurred in 6% of obe-cel vs. 32% of brexu-cel pts (p = 0.0027). Among the obe-cel pts, CRS occurred in 31% after the first infusion and 46% after the second; ICANS occurred in 3% after the first infusion and 15% after the second. Prolonged Gr4 neutropenia (ANC < 500 cells/uL beyond day 30 from infusion) occurred in 24% of obe-cel vs. 28% of brexu-cel pts (p = 0.73). Deaths within the first 28 days of infusion occurred in 0 obe-cel pts and 4 brexu-cel pts (2 of infection, 1 of infection/brain bleed, and 1 of liver failure in the setting of Gr4 CRS and HLH).</div><div>Response rates were high and did not significantly differ between cohorts (p = 0.85) (Table 3). 81% of obe-cel pts vs. 80% of brexu-cel pts achieved an MRD- CR/CRi.</div></div><div><h3>Conclusion</h3><div>Pts selected for obe-cel apheresis were similar to those for brexu-cel over the study period (noting that not all centers had access to obe-cel during this time). Similar to clinical trial results, obe-cel was associated with lower rates of CRS/ICANS. Rates of MRD-negative CR were high and did not differ between cohorts. A larger sample and longer follow up are required for further anal","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S27-S29"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098561","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.2025.12.101
Dustin A Cobb PhD , Lixia Liu MD , Amanda M Lulu PhD , Daniel W. Lee MD
<div><h3>Introduction</h3><div>Barriers to successful CAR T cell therapy include exhaustion, lack of persistence, competitive metabolic demands, and associated toxicities. Responses are characterized by rapid expansion and a robust and multidimensional proinflammatory state. CAR T cells currently lack a means of control. In contrast, T cell receptor engagement results in productive activation yet is balanced by immune checkpoint receptors which regulate activity and maintain homeostasis. Our goal is to temper the CAR T cell response by introducing a system of autoregulation to counter the potent activation delivered via the CAR receptor. We designed a chimeric inhibitory receptor (CIR), consisting of an IFN-gamma binding domain coupled to the inhibitory signaling domain of TIGIT, to provide negative signaling in response to high levels of CAR activation and IFN-g (Fig1A).</div></div><div><h3>Methods</h3><div>An anti-IFN-g scFv followed by the TIGIT intracellular domain was co-expressed with a CD19 CAR and either a CD28 or 4-1BB costimulatory domain. Gene expression profiling was performed using Nanostring nCounter analysis. Activation state following stimulation with CD19<sup>+</sup> NALM-6 tumor cells was evaluated by flow cytometry. Single-cell secretome measurements were evaluated by Isolight analysis. NSG mice were injected with NALM-6 tumor cells and two days later with CAR T cells.</div></div><div><h3>Results</h3><div>CAR.CIR T cell gene expression revealed attenuation across multiple major T-cell signaling pathways including JAK-STAT, PI3-Kinase, and NFAT with an accompanying shift in metabolic re-programming relative to CD19 controls following stimulation (Fig1B). Attenuated activation was confirmed by a reduction in activation marker expression (Fig2A). Despite attenuation, CIR-expressing CD19 CARs exhibited normal cytotoxicity. Monocyte-derived macrophage and dendritic cell activation by CAR.CIR T cells were reduced as evidenced by decreased secretion of myeloid cell-derived proinflammatory mediators. Preliminary analysis of the secretome suggests improved polyfunctionality of CAR.CIR T cells, an indicator of increased clinical efficacy (Fig2B). CAR.CIR T cells also exhibited a reduction in PD-1, LAG-3, and TIM-3 following in vitro continuous antigen exposure (Fig2C), suggesting improved resistance to exhaustion. Importantly, in vivo anti-tumor responses were not adversely affected as CAR.CIR T cells efficiently controlled disease in leukemia-bearing mice (Fig2D). Similar results were recapitulated in 4-1BB-costimulated CARs, highlighting broader potential clinical applicability.</div></div><div><h3>Conclusion</h3><div>Self-regulation in CAR T cells may confer advantages such as tempered activation, improved functionality and metabolic fitness, and enhanced persistence. These results provide a compelling proof of concept of an innovative auto-regulating CAR T cell design with the potential to improve responses and mitigate severe toxici
{"title":"Development of “Auto-Regulating” CD19 CAR T cells Using a Novel Chimeric Inhibitory Receptor","authors":"Dustin A Cobb PhD , Lixia Liu MD , Amanda M Lulu PhD , Daniel W. Lee MD","doi":"10.1016/j.jtct.2025.12.101","DOIUrl":"10.1016/j.jtct.2025.12.101","url":null,"abstract":"<div><h3>Introduction</h3><div>Barriers to successful CAR T cell therapy include exhaustion, lack of persistence, competitive metabolic demands, and associated toxicities. Responses are characterized by rapid expansion and a robust and multidimensional proinflammatory state. CAR T cells currently lack a means of control. In contrast, T cell receptor engagement results in productive activation yet is balanced by immune checkpoint receptors which regulate activity and maintain homeostasis. Our goal is to temper the CAR T cell response by introducing a system of autoregulation to counter the potent activation delivered via the CAR receptor. We designed a chimeric inhibitory receptor (CIR), consisting of an IFN-gamma binding domain coupled to the inhibitory signaling domain of TIGIT, to provide negative signaling in response to high levels of CAR activation and IFN-g (Fig1A).</div></div><div><h3>Methods</h3><div>An anti-IFN-g scFv followed by the TIGIT intracellular domain was co-expressed with a CD19 CAR and either a CD28 or 4-1BB costimulatory domain. Gene expression profiling was performed using Nanostring nCounter analysis. Activation state following stimulation with CD19<sup>+</sup> NALM-6 tumor cells was evaluated by flow cytometry. Single-cell secretome measurements were evaluated by Isolight analysis. NSG mice were injected with NALM-6 tumor cells and two days later with CAR T cells.</div></div><div><h3>Results</h3><div>CAR.CIR T cell gene expression revealed attenuation across multiple major T-cell signaling pathways including JAK-STAT, PI3-Kinase, and NFAT with an accompanying shift in metabolic re-programming relative to CD19 controls following stimulation (Fig1B). Attenuated activation was confirmed by a reduction in activation marker expression (Fig2A). Despite attenuation, CIR-expressing CD19 CARs exhibited normal cytotoxicity. Monocyte-derived macrophage and dendritic cell activation by CAR.CIR T cells were reduced as evidenced by decreased secretion of myeloid cell-derived proinflammatory mediators. Preliminary analysis of the secretome suggests improved polyfunctionality of CAR.CIR T cells, an indicator of increased clinical efficacy (Fig2B). CAR.CIR T cells also exhibited a reduction in PD-1, LAG-3, and TIM-3 following in vitro continuous antigen exposure (Fig2C), suggesting improved resistance to exhaustion. Importantly, in vivo anti-tumor responses were not adversely affected as CAR.CIR T cells efficiently controlled disease in leukemia-bearing mice (Fig2D). Similar results were recapitulated in 4-1BB-costimulated CARs, highlighting broader potential clinical applicability.</div></div><div><h3>Conclusion</h3><div>Self-regulation in CAR T cells may confer advantages such as tempered activation, improved functionality and metabolic fitness, and enhanced persistence. These results provide a compelling proof of concept of an innovative auto-regulating CAR T cell design with the potential to improve responses and mitigate severe toxici","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S67-S68"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098567","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}
Topic Significance & Study Purpose/Background/Rationale
Bispecific T-cell Engager (BiTE) therapies effectively treat hematologic cancers and are expanding to solid tumors. These therapies traditionally require hospital administration due to risks such as cytokine release syndrome (CRS) and neurotoxicity. However, transitioning BiTE delivery to outpatient settings can improve access, reduce hospital burden, and enhance the overall patient experience.
Methods, Intervention, & Analysis
In 2023, the practice expanded its Transplant and Cellular Therapy (TCT) clinic to include outpatient BiTE therapy. Leveraging its CAR-T experience, the team developed a structured workflow. After physician evaluation, nurses coordinate insurance, pre-treatment testing, and patient education. Caregivers monitor and document ICE (Immune Effector Cell-Associated Encephalopathy) scores and temperatures three times daily during the step-up phase. Patients receive oral dexamethasone for overnight management of potential CRS or neurotoxicity. If ICE scores drop below 10 or temperatures exceed 100.4°F, caregivers contact a 24/7 nurse line, which coordinates with the on-call physician. Most adverse events are managed at home with oral dexamethasone and Tylenol, with IV dexamethasone or tocilizumab availability at the clinic.
Findings & Interpretation
Between March 2023 and July 2025, the TCT clinic treated 61 patients with outpatient BiTEs including Teclistamab, Talquetamab, Epcoritamab, Mosunetuzumab, Glofitamab, and Tarlatamab. CRS occurred in 41% of patients (all grade 1–2), with no grade 3–4 CRS or neurotoxicity. Seven patients required admission, though only one was for CRS. Other reasons included disease progression, pain control, hypercalcemia, and bowel perforation. Three patients could not complete step-up dosing due to disease progression and death.
Discussion & Implications
This model demonstrates that outpatient BiTE therapy is feasible and safe in a community setting. With structured protocols, nursing support, and caregiver engagement, complex therapies can be delivered outside the hospital, expanding access and reinforcing the vital role of oncology nurses in advanced outpatient care.
{"title":"Outpatient Administration of Bispecific Therapies in a Community Oncology Setting","authors":"Julia Grubbs RN, BSN, BMTCN , Tiffany Hopper MSN, RN, OCN","doi":"10.1016/j.jtct.2025.12.116","DOIUrl":"10.1016/j.jtct.2025.12.116","url":null,"abstract":"<div><h3>Topic Significance & Study Purpose/Background/Rationale</h3><div>Bispecific T-cell Engager (BiTE) therapies effectively treat hematologic cancers and are expanding to solid tumors. These therapies traditionally require hospital administration due to risks such as cytokine release syndrome (CRS) and neurotoxicity. However, transitioning BiTE delivery to outpatient settings can improve access, reduce hospital burden, and enhance the overall patient experience.</div></div><div><h3>Methods, Intervention, & Analysis</h3><div>In 2023, the practice expanded its Transplant and Cellular Therapy (TCT) clinic to include outpatient BiTE therapy. Leveraging its CAR-T experience, the team developed a structured workflow. After physician evaluation, nurses coordinate insurance, pre-treatment testing, and patient education. Caregivers monitor and document ICE (Immune Effector Cell-Associated Encephalopathy) scores and temperatures three times daily during the step-up phase. Patients receive oral dexamethasone for overnight management of potential CRS or neurotoxicity. If ICE scores drop below 10 or temperatures exceed 100.4°F, caregivers contact a 24/7 nurse line, which coordinates with the on-call physician. Most adverse events are managed at home with oral dexamethasone and Tylenol, with IV dexamethasone or tocilizumab availability at the clinic.</div></div><div><h3>Findings & Interpretation</h3><div>Between March 2023 and July 2025, the TCT clinic treated 61 patients with outpatient BiTEs including Teclistamab, Talquetamab, Epcoritamab, Mosunetuzumab, Glofitamab, and Tarlatamab. CRS occurred in 41% of patients (all grade 1–2), with no grade 3–4 CRS or neurotoxicity. Seven patients required admission, though only one was for CRS. Other reasons included disease progression, pain control, hypercalcemia, and bowel perforation. Three patients could not complete step-up dosing due to disease progression and death.</div></div><div><h3>Discussion & Implications</h3><div>This model demonstrates that outpatient BiTE therapy is feasible and safe in a community setting. With structured protocols, nursing support, and caregiver engagement, complex therapies can be delivered outside the hospital, expanding access and reinforcing the vital role of oncology nurses in advanced outpatient care.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S82-S83"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098568","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.2025.12.065
Dimana Dimitrova MD , Gulbu Uzel MD , Amanda K. Ombrello MD , Jeffrey I. Cohen MD , Jessica Durkee-Shock MD , Jessenia Campos RN , Amy Chai RN , Alison C Cusmano DNP , Mustafa A. Hyder MD , Ralph Mangusan DNP , Kamil A. Rechache MD , Ruby Sabina NP , Kristen M. Cole BSN , Judy L. Baruffaldi BA , Jennifer Wilder DNP , Katherine R. Calvo MD, PhD , Jennifer Cuellar-Rodriguez MD , Mary Czech MD , Elaine Jaffe MD , Luigi D. Notarangelo MD , Jennifer A. Kanakry MD
<div><div>HCT is a potential definitive therapy in patients with disorders hallmarked by severe dysregulation or uncontrolled proliferation of T cells, whether in the setting of a primary immune regulatory disorder (P-IRD) or secondary IRD, such as T cell chronic active EBV (CAEBV). These patients are at high risk of graft failure (GF) and/or disease progression but may also enter HCT with significant comorbidities requiring a low toxicity approach.</div><div>Children and adults (n=25), median age 24 years (range 5-62), received a distal equine ATG-based, radiation free, reduced intensity conditioning, posttransplantation cyclophosphamide (PTCy)-based platform (<strong>Fig 1</strong>) intended to optimize host T cell depletion prior to HCT without compromising post-HCT immune reconstitution or graft vs tumor immunity (GVT), minimize severe graft versus host disease (GVHD) and toxicities, and allow alternative donor use. This high-risk cohort had median HCT comorbidity index score of 3 (range 0-11), with active lymphoma or aggressive lymphoproliferative disorder in 36% at HCT. Mismatched grafts were commonly used (44%); all grafts were T replete. Patient and donor characteristics are detailed in <strong>Fig 2</strong>.</div><div>With median follow up of 4.4 years (range 1-7), 2 year overall and GF-free survival were estimated at 84% and 80% respectively, with one secondary GF followed by successful retransplant, <strong>Fig 3A</strong>. Patients with PIRD entities involving hyperactivation of the PI3K/Akt/mTOR pathway (n=8), 1 with prior history of GF, universally engrafted without need for further donor lymphocyte infusions (DLI). Declining donor T chimerism without clinical symptoms was successfully rescued by DLI in 1 CAEBV patient, while 3 other patients required DLI for progression of peripheral T-cell lymphoma (PTCL, n=1) or CAEBV-associated lymphoproliferative disorder (n=2). Of 5 CAEBV patients, disease progression occurred only in these latter two - the only ones to receive ruxolitinib in the peri-HCT period for control of underlying hemophagocytic lymphohistiocytosis - and this may have altered reconstitution of T cell compartments required for successful GVT.</div><div>Acute GVHD rates were low, with grade I GVHD in 4 patients and grade II acute GVHD in 3 patients, one s/p donor lymphocyte infusion, for a 1-year grade II-IV cumulative incidence of 12%, <strong>Fig 3B</strong>. An additional patient developed overlap syndrome following multiple DLI in the setting of disease progression. Only 2 further patients required brief topical therapy for mild chronic GVHD of the skin, while, remarkably, no other patients developed any chronic GVHD requiring systemic therapy.</div><div>This novel approach shows great promise in patients with IRD and is concurrently under study in patients with relapsed/refractory PTCL in absence of underlying immune defects, also with encouraging outcomes. Continued follow up is needed to confirm long-term graft st
{"title":"Ptcy-Based Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with Immune Regulation Disorders of T cells Using Distal Equine ATG Affords Successful Engraftment with Low GVHD Incidence","authors":"Dimana Dimitrova MD , Gulbu Uzel MD , Amanda K. Ombrello MD , Jeffrey I. Cohen MD , Jessica Durkee-Shock MD , Jessenia Campos RN , Amy Chai RN , Alison C Cusmano DNP , Mustafa A. Hyder MD , Ralph Mangusan DNP , Kamil A. Rechache MD , Ruby Sabina NP , Kristen M. Cole BSN , Judy L. Baruffaldi BA , Jennifer Wilder DNP , Katherine R. Calvo MD, PhD , Jennifer Cuellar-Rodriguez MD , Mary Czech MD , Elaine Jaffe MD , Luigi D. Notarangelo MD , Jennifer A. Kanakry MD","doi":"10.1016/j.jtct.2025.12.065","DOIUrl":"10.1016/j.jtct.2025.12.065","url":null,"abstract":"<div><div>HCT is a potential definitive therapy in patients with disorders hallmarked by severe dysregulation or uncontrolled proliferation of T cells, whether in the setting of a primary immune regulatory disorder (P-IRD) or secondary IRD, such as T cell chronic active EBV (CAEBV). These patients are at high risk of graft failure (GF) and/or disease progression but may also enter HCT with significant comorbidities requiring a low toxicity approach.</div><div>Children and adults (n=25), median age 24 years (range 5-62), received a distal equine ATG-based, radiation free, reduced intensity conditioning, posttransplantation cyclophosphamide (PTCy)-based platform (<strong>Fig 1</strong>) intended to optimize host T cell depletion prior to HCT without compromising post-HCT immune reconstitution or graft vs tumor immunity (GVT), minimize severe graft versus host disease (GVHD) and toxicities, and allow alternative donor use. This high-risk cohort had median HCT comorbidity index score of 3 (range 0-11), with active lymphoma or aggressive lymphoproliferative disorder in 36% at HCT. Mismatched grafts were commonly used (44%); all grafts were T replete. Patient and donor characteristics are detailed in <strong>Fig 2</strong>.</div><div>With median follow up of 4.4 years (range 1-7), 2 year overall and GF-free survival were estimated at 84% and 80% respectively, with one secondary GF followed by successful retransplant, <strong>Fig 3A</strong>. Patients with PIRD entities involving hyperactivation of the PI3K/Akt/mTOR pathway (n=8), 1 with prior history of GF, universally engrafted without need for further donor lymphocyte infusions (DLI). Declining donor T chimerism without clinical symptoms was successfully rescued by DLI in 1 CAEBV patient, while 3 other patients required DLI for progression of peripheral T-cell lymphoma (PTCL, n=1) or CAEBV-associated lymphoproliferative disorder (n=2). Of 5 CAEBV patients, disease progression occurred only in these latter two - the only ones to receive ruxolitinib in the peri-HCT period for control of underlying hemophagocytic lymphohistiocytosis - and this may have altered reconstitution of T cell compartments required for successful GVT.</div><div>Acute GVHD rates were low, with grade I GVHD in 4 patients and grade II acute GVHD in 3 patients, one s/p donor lymphocyte infusion, for a 1-year grade II-IV cumulative incidence of 12%, <strong>Fig 3B</strong>. An additional patient developed overlap syndrome following multiple DLI in the setting of disease progression. Only 2 further patients required brief topical therapy for mild chronic GVHD of the skin, while, remarkably, no other patients developed any chronic GVHD requiring systemic therapy.</div><div>This novel approach shows great promise in patients with IRD and is concurrently under study in patients with relapsed/refractory PTCL in absence of underlying immune defects, also with encouraging outcomes. Continued follow up is needed to confirm long-term graft st","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S41"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098700","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.2025.12.068
Leena Babiker MS , Léolène J Carrington PhD , Riley Outen BS , José A Villegas Vazquez PhD , Katlyn Lederer BS , Anneka Allman BA , Brandon Zhou BA , Burkhard Ludewig VMD, PhD , Shovik Bandyopadhyay MD, PhD , Leonardo Scarpellino BS , Kai Tan PhD , Ronjon Chakraverty MD, PhD , Michael J May PhD , Sanjiv A Luther PhD , Laura Vella MD, PhD , Ivan Maillard MD, PhD
<div><h3>Background</h3><div>Allogeneic hematopoietic cell transplantation (allo-HCT) can cure multiple hematologic disorders, but graft-versus-host disease (GVHD) compromises outcomes. Past work suggests that pathogenic donor T cells can damage lymph node fibroblastic reticular cells (FRCs) during GVHD, thus undermining the specialized infrastructure and functions of peripheral LNs (pLNs) (Tsao, 2009; Suenaga, 2015; Dertschnig, 2020). Yet, the mechanisms, relative importance and functional consequences of LN GVHD remain incompletely understood.</div></div><div><h3>Methods</h3><div>We used mouse allo-HCT models (C57BL/6→B6×BALB/c F1 and C57BL/6→BALB/c), titrating T-cell doses to elicit sublethal GVHD. We assessed pLN stromal subsets by flow cytometry and lineage tracing, single-cell RNA-seq, and immunofluorescence. Trafficking was tested via adoptive transfer of naïve and polyclonal cells. Mechanisms and reversibility were probed by administering Flt3L-cultured, LPS-activated bone-marrow–derived DCs or an agonistic anti-LTβR antibody.</div></div><div><h3>Objectives</h3><div>To characterize LN damage in GVHD, determine its impact on lymphocyte homing and architecture, and test whether loss of dendritic cell (DC)–dependent lymphotoxin-β receptor (LTβR) signaling contributes to high endothelial venule (HEV) collapse and is therapeutically reversible.</div></div><div><h3>Results</h3><div>Despite only modest thymic impairment at day 30–60, pLNs from GVHD mice showed loss of CD31⁻PDPN⁺ FRCs. MAdCAM<sup>hi</sup> and CD157<sup>hi</sup> FRCs lineage-traced with a Ccl19-Cre transgene were profoundly depleted. MAdCAM<sup>hi</sup>CD157<sup>hi</sup> floor-lymphatic endothelial cells (LECs) virtually disappeared, and HEVs exhibited flattened morphology with reduced PNAd expression (Figure 1). Single-cell RNA-seq corroborated loss of floor LECs, marginal reticular cells, and Ccl19<sup>+</sup>/Ccl21⁺ T-zone FRCs, with residual stroma skewed toward collagen-rich Cxcl14⁺ fibroblasts. Immunofluorescence imaging revealed B cell depletion, loss of Desmin<sup>+</sup> FRCs, disrupted subcapsular sinus and increased collagen deposition. GVHD pLNs contained fewer naïve B and T-cells and were less receptive than spleen to homing of adoptively transferred naïve and polyclonal lymphocytes (Figure 2). Kinetic analysis revealed early LEC injury (day 7) followed by FRC loss (day 14). Importantly, DC subsets were reduced in pLNs and expressed less LTβ, suggesting impaired DC-driven LTβR signaling in HEV collapse during GVHD (Moussion, 2011). To assess reversibility, we administered bone marrow-derived DCs or an agonistic anti-LTβ-receptor antibody after allo-HCT. Both interventions increased PNAd HEV expression and partially restored entry of naïve T-cells and polyclonal lymphocytes into pLNs.</div></div><div><h3>Conclusions</h3><div>These findings identify DC depletion and attenuated LTβR signaling as drivers of HEV failure in LN GVHD and highlight DC–stroma crosstalk as a tra
{"title":"Early Dendritic Cell Depletion Drives High Endothelial Venule Dysfunction and Failure of Naïve Lymphocyte Trafficking in Lymph Node Graft-Versus-Host Disease","authors":"Leena Babiker MS , Léolène J Carrington PhD , Riley Outen BS , José A Villegas Vazquez PhD , Katlyn Lederer BS , Anneka Allman BA , Brandon Zhou BA , Burkhard Ludewig VMD, PhD , Shovik Bandyopadhyay MD, PhD , Leonardo Scarpellino BS , Kai Tan PhD , Ronjon Chakraverty MD, PhD , Michael J May PhD , Sanjiv A Luther PhD , Laura Vella MD, PhD , Ivan Maillard MD, PhD","doi":"10.1016/j.jtct.2025.12.068","DOIUrl":"10.1016/j.jtct.2025.12.068","url":null,"abstract":"<div><h3>Background</h3><div>Allogeneic hematopoietic cell transplantation (allo-HCT) can cure multiple hematologic disorders, but graft-versus-host disease (GVHD) compromises outcomes. Past work suggests that pathogenic donor T cells can damage lymph node fibroblastic reticular cells (FRCs) during GVHD, thus undermining the specialized infrastructure and functions of peripheral LNs (pLNs) (Tsao, 2009; Suenaga, 2015; Dertschnig, 2020). Yet, the mechanisms, relative importance and functional consequences of LN GVHD remain incompletely understood.</div></div><div><h3>Methods</h3><div>We used mouse allo-HCT models (C57BL/6→B6×BALB/c F1 and C57BL/6→BALB/c), titrating T-cell doses to elicit sublethal GVHD. We assessed pLN stromal subsets by flow cytometry and lineage tracing, single-cell RNA-seq, and immunofluorescence. Trafficking was tested via adoptive transfer of naïve and polyclonal cells. Mechanisms and reversibility were probed by administering Flt3L-cultured, LPS-activated bone-marrow–derived DCs or an agonistic anti-LTβR antibody.</div></div><div><h3>Objectives</h3><div>To characterize LN damage in GVHD, determine its impact on lymphocyte homing and architecture, and test whether loss of dendritic cell (DC)–dependent lymphotoxin-β receptor (LTβR) signaling contributes to high endothelial venule (HEV) collapse and is therapeutically reversible.</div></div><div><h3>Results</h3><div>Despite only modest thymic impairment at day 30–60, pLNs from GVHD mice showed loss of CD31⁻PDPN⁺ FRCs. MAdCAM<sup>hi</sup> and CD157<sup>hi</sup> FRCs lineage-traced with a Ccl19-Cre transgene were profoundly depleted. MAdCAM<sup>hi</sup>CD157<sup>hi</sup> floor-lymphatic endothelial cells (LECs) virtually disappeared, and HEVs exhibited flattened morphology with reduced PNAd expression (Figure 1). Single-cell RNA-seq corroborated loss of floor LECs, marginal reticular cells, and Ccl19<sup>+</sup>/Ccl21⁺ T-zone FRCs, with residual stroma skewed toward collagen-rich Cxcl14⁺ fibroblasts. Immunofluorescence imaging revealed B cell depletion, loss of Desmin<sup>+</sup> FRCs, disrupted subcapsular sinus and increased collagen deposition. GVHD pLNs contained fewer naïve B and T-cells and were less receptive than spleen to homing of adoptively transferred naïve and polyclonal lymphocytes (Figure 2). Kinetic analysis revealed early LEC injury (day 7) followed by FRC loss (day 14). Importantly, DC subsets were reduced in pLNs and expressed less LTβ, suggesting impaired DC-driven LTβR signaling in HEV collapse during GVHD (Moussion, 2011). To assess reversibility, we administered bone marrow-derived DCs or an agonistic anti-LTβ-receptor antibody after allo-HCT. Both interventions increased PNAd HEV expression and partially restored entry of naïve T-cells and polyclonal lymphocytes into pLNs.</div></div><div><h3>Conclusions</h3><div>These findings identify DC depletion and attenuated LTβR signaling as drivers of HEV failure in LN GVHD and highlight DC–stroma crosstalk as a tra","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S43"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098702","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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