Pub Date : 2026-02-01DOI: 10.1016/S2666-6367(26)00033-3
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Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.953
Monzr M. Al Malki MD , Stephanie Bo-Subait MPH , Brent R. Logan PhD , Sarah Smith RN, BSN , Erin Leckrone MBA , Dr. Heather E. Stefanski MD, PhD , Dr. Jeffery J. Auletta MD , Stephen R. Spellman MBS , Craig Malmberg BS , Medhat Askar MD, PhD , Rachel Cusatis PhD , Brian C. Shaffer MD, MS , Dipenkumar Modi MD , Farhad Khimani MD , Mahasweta Gooptu MD , Mehdi Hamadani MD , Martin Maiers MS , Joseph Stanek MS , Javier Bolaños Meade MD , Uttam Rao MD, MBA , Antonio M. Jimenez Jimenez MD
<div><h3>Background</h3><div>Access to allogeneic hematopoietic cell transplantation (HCT) remains limited for patients of non-European ancestry due to donor unavailability. While 7/8 mismatched unrelated donors (MMUD) provide acceptable outcomes, HCT with ≥2 allele mismatches (<7/8) have historically yielded poor survival and prohibitive toxicity. Post-transplant cyclophosphamide (PTCy) has significantly improved outcomes after MMUD HCT, but the prognostic effect of increasing HLA disparity in this setting is unclear.</div></div><div><h3>Methods</h3><div>The prospective ACCESS trial (NCT04904588) evaluated PTCy-based GVHD prophylaxis in adults receiving 4–7/8 HLA-mismatched peripheral blood stem cells (PBSC) from donors ≤35 years old after myeloablative (MAC) or reduced-intensity/non-myeloablative (RIC/NMA) conditioning. Primary endpoint was 1-year overall survival (OS). Secondary endpoints included graft failure, non-relapse mortality (NRM), relapse, acute and chronic GVHD, and GVHD-free relapse-free survival (GRFS).</div></div><div><h3>Results</h3><div>Among 268 adults, 85 received <7/8 and 183 received 7/8 MMUD PBSC grafts. The <7/8 cohort (median age 57, range 24–78; 49% male) was racially diverse, with the majority (61%) identifying as racial/ethnic groups other than non-Hispanic White, and included 6/8 (82%), 5/8 (14%), and 4/8 (4%) matches. Conditioning intensity in this group was MAC (n=23) and RIC/NMA (n=62). Diagnoses included AML (55%), MDS (15%), lymphoma (14%) and ALL (11%). Most received fludarabine/melphalan (44%) or myeloablative busulfan/fludarabine (21%); the median CD34+ cell dose was 5.5 × 10^6/kg, and 75% of grafts were cryopreserved. The 7/8 group (median age 63, range 20–79; 52% male) had similar disease distribution, conditioning intensity [MAC (n=52), RIC/NMA (n=131)], and infused cell dose. In this cohort, 61% of grafts were cryopreserved, and nearly half (45%) identified as racial/ethnic groups other than non-Hispanic White.</div><div>At 1 year, OS was 86% (95% CI, 76–92) for <7/8 vs 79% (72–84) for 7/8. Relapse was 23% (14–33) vs 17% (12–23); NRM 8% (4–16) vs 14% (9–19); and GRFS 55% (43–65) vs 51% (44–58) in <7/8 and 7/8, respectively. At 6 months, grade II–IV acute GVHD occurred in 34% (24–44) vs 39% (32–46), and grade III–IV in 7% (3–14) vs 8% (5–13) in <7/8 and 7/8, respectively. At 1 year, moderate/severe chronic GVHD was 8% (3–15) vs 11% (7–16). Primary graft failure occurred only after RIC/NMA: 8% (3–18) with <7/8 vs 3% (1–8) with 7/8.</div><div>In <7/8 recipients, 1-year OS was 91% with MAC and 84% with RIC/NMA; relapse 32% vs 20%; GRFS 53% vs 55%; and NRM 9% vs 8%, respectively.</div></div><div><h3>Conclusions</h3><div>PTCy-based GVHD prophylaxis results in excellent outcomes following <7/8 MMUD HCT, with OS >80% and low NRM and GVHD, comparable to 7/8. Extending donor criteria to 4–6/8 mismatches should broaden equitable donor access while permitting optimization of non-HLA fact
{"title":"Expanding Donor Access: Comparable One Year Outcomes in 4–6/8 and 7/8 Mismatched Unrelated Donor Transplantation with Ptcy-Based GVHD Prophylaxis (ACCESS Trial)","authors":"Monzr M. Al Malki MD , Stephanie Bo-Subait MPH , Brent R. Logan PhD , Sarah Smith RN, BSN , Erin Leckrone MBA , Dr. Heather E. Stefanski MD, PhD , Dr. Jeffery J. Auletta MD , Stephen R. Spellman MBS , Craig Malmberg BS , Medhat Askar MD, PhD , Rachel Cusatis PhD , Brian C. Shaffer MD, MS , Dipenkumar Modi MD , Farhad Khimani MD , Mahasweta Gooptu MD , Mehdi Hamadani MD , Martin Maiers MS , Joseph Stanek MS , Javier Bolaños Meade MD , Uttam Rao MD, MBA , Antonio M. Jimenez Jimenez MD","doi":"10.1016/j.jtct.2025.12.953","DOIUrl":"10.1016/j.jtct.2025.12.953","url":null,"abstract":"<div><h3>Background</h3><div>Access to allogeneic hematopoietic cell transplantation (HCT) remains limited for patients of non-European ancestry due to donor unavailability. While 7/8 mismatched unrelated donors (MMUD) provide acceptable outcomes, HCT with ≥2 allele mismatches (<7/8) have historically yielded poor survival and prohibitive toxicity. Post-transplant cyclophosphamide (PTCy) has significantly improved outcomes after MMUD HCT, but the prognostic effect of increasing HLA disparity in this setting is unclear.</div></div><div><h3>Methods</h3><div>The prospective ACCESS trial (NCT04904588) evaluated PTCy-based GVHD prophylaxis in adults receiving 4–7/8 HLA-mismatched peripheral blood stem cells (PBSC) from donors ≤35 years old after myeloablative (MAC) or reduced-intensity/non-myeloablative (RIC/NMA) conditioning. Primary endpoint was 1-year overall survival (OS). Secondary endpoints included graft failure, non-relapse mortality (NRM), relapse, acute and chronic GVHD, and GVHD-free relapse-free survival (GRFS).</div></div><div><h3>Results</h3><div>Among 268 adults, 85 received <7/8 and 183 received 7/8 MMUD PBSC grafts. The <7/8 cohort (median age 57, range 24–78; 49% male) was racially diverse, with the majority (61%) identifying as racial/ethnic groups other than non-Hispanic White, and included 6/8 (82%), 5/8 (14%), and 4/8 (4%) matches. Conditioning intensity in this group was MAC (n=23) and RIC/NMA (n=62). Diagnoses included AML (55%), MDS (15%), lymphoma (14%) and ALL (11%). Most received fludarabine/melphalan (44%) or myeloablative busulfan/fludarabine (21%); the median CD34+ cell dose was 5.5 × 10^6/kg, and 75% of grafts were cryopreserved. The 7/8 group (median age 63, range 20–79; 52% male) had similar disease distribution, conditioning intensity [MAC (n=52), RIC/NMA (n=131)], and infused cell dose. In this cohort, 61% of grafts were cryopreserved, and nearly half (45%) identified as racial/ethnic groups other than non-Hispanic White.</div><div>At 1 year, OS was 86% (95% CI, 76–92) for <7/8 vs 79% (72–84) for 7/8. Relapse was 23% (14–33) vs 17% (12–23); NRM 8% (4–16) vs 14% (9–19); and GRFS 55% (43–65) vs 51% (44–58) in <7/8 and 7/8, respectively. At 6 months, grade II–IV acute GVHD occurred in 34% (24–44) vs 39% (32–46), and grade III–IV in 7% (3–14) vs 8% (5–13) in <7/8 and 7/8, respectively. At 1 year, moderate/severe chronic GVHD was 8% (3–15) vs 11% (7–16). Primary graft failure occurred only after RIC/NMA: 8% (3–18) with <7/8 vs 3% (1–8) with 7/8.</div><div>In <7/8 recipients, 1-year OS was 91% with MAC and 84% with RIC/NMA; relapse 32% vs 20%; GRFS 53% vs 55%; and NRM 9% vs 8%, respectively.</div></div><div><h3>Conclusions</h3><div>PTCy-based GVHD prophylaxis results in excellent outcomes following <7/8 MMUD HCT, with OS >80% and low NRM and GVHD, comparable to 7/8. Extending donor criteria to 4–6/8 mismatches should broaden equitable donor access while permitting optimization of non-HLA fact","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S74-S75"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098476","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.2025.12.954
Amreen A. Imrit BASc , Dionne M. Aleman PhD , Auro Viswabandya MD , Fotios V. Michelis MD, PhD
Introduction
Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative in the treatment of various hematologic malignancies but is associated with significant morbidity and mortality. Predictive modeling using machine learning (ML) has gained traction in this field, yet challenges such as survival imbalance and the difficulty of long-term prediction persist.
Objectives
To apply a specialized ML method to data from our allo-HCT registry in an attempt to address these issues.
Methods
Our single-center cohort included 2043 patients that underwent allo-HCT from January 2010 to September 2024 at the Princess Maragret Cancer Centre in Toronto, Canada. Using data from our program database, we applied the recently developed Classification-Augmented Survival Estimation (CASE) method (Shourabizadeh et al, PLoS One 2025;20(1):e0315928), which augments survival data and improves class balance when predicting 10-year post-transplant survival. This approach increased the minority survival proportion from 18% to 38%, improving model performance (F1-score: 0.75 vs. 0.71). We then employed SHAP (SHapley Additive Explanations) to identify key clinical factors and feature interactions within the ML model influencing survival over time.
Results
A consistent and clinically meaningful interaction emerged between patient age and donor age; older patients transplanted using younger donors demonstrated improved survival compared to older patient–older donor pairs (p-value=0.017). Using SHAP interaction plots and log-rank tests, we identified optimal cutoff groups of patient age ≤65 and donor age ≤30, with patients >65 performing best when donor age ≤30 (Figure A)(Overall p-value <0.001). Subgroup analysis by donor type revealed that this trend was most pronounced for HLA haploidentical (Figure B)(overall p-value <0.0001), with an ideal subgroup cutoff of patient age >50, donor age ≤30. Older haploidentical transplants using younger donors demonstrated borderline significant superiority over older patients using older donors (p-value=0.06). Donor and recipient age interaction was also significant for unrelated fully matched transplants (overall p-value 0.01), while matched related transplants for older patients (>61 years) exhibited poorer outcomes using younger donors (≤56 years) compared to older donors (>56 years)(p=0.04).
Conclusion
These findings highlight the potential of combining advanced ML augmentation and explainable AI techniques to uncover complex relationships in allo-HCT outcomes, while also underscoring the need for further validation in larger, independent cohorts.
同种异体造血细胞移植（allogeneic hematopoietic cell transplantation, allo-HCT）在治疗多种血液系统恶性肿瘤方面具有潜在的疗效，但与显著的发病率和死亡率相关。使用机器学习（ML）的预测建模在这一领域已经获得了牵引力，但诸如生存不平衡和长期预测困难等挑战仍然存在。目的应用一种专门的ML方法来处理来自我们的allow - hct注册表的数据，试图解决这些问题。方法本研究纳入了2010年1月至2024年9月在加拿大多伦多玛格丽特公主癌症中心接受allo-HCT治疗的2043例患者。利用我们的程序数据库中的数据，我们应用了最近开发的分类增强生存估计（CASE）方法（Shourabizadeh等人，PLoS One 2025;20(1):e0315928），该方法在预测移植后10年生存时增加了生存数据并改善了分类平衡。该方法将少数群体存活率从18%提高到38%，提高了模型性能（f1评分：0.75 vs. 0.71）。然后，我们使用SHAP （SHapley加性解释）来确定ML模型中随时间影响生存的关键临床因素和特征相互作用。结果患者年龄与供体年龄之间存在一致且具有临床意义的相互作用；与老年患者-老年供体对相比，使用年轻供体进行移植的老年患者生存率更高（p值=0.017）。通过SHAP交互作用图和log-rank检验，我们确定了患者年龄≤65岁和供者年龄≤30岁的最佳截断组，供者年龄≤30岁时，患者年龄≤65岁表现最佳（图A）（总p值<；0.001）。按供体类型进行的亚组分析显示，这种趋势在HLA单倍相同的人群中最为明显（图B）（总p值<；0.0001），理想的亚组截止值为患者年龄>；50，供体年龄≤30。使用年轻供体的老年患者单倍体移植比使用老年供体的老年患者具有显著的边缘性优势（p值=0.06）。对于不相关的完全匹配移植，供体和受体年龄的相互作用也很显著（总p值0.01），而对于老年患者（>；61岁），使用年轻供体（≤56岁）的匹配相关移植比使用老年供体（>；56岁）的匹配相关移植结果更差（p=0.04）。这些发现强调了将先进的ML增强技术与可解释的AI技术相结合的潜力，以揭示异位hct结果的复杂关系，同时也强调了需要在更大的独立队列中进一步验证。
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Pub Date : 2026-02-01DOI: 10.1016/j.jtct.2025.12.955
Megan M. Herr PhD , Nisha M. Nair MS, MPH , Shernan Holtan MD , Nandita Khera MD, MPH , Theresa E. Hahn PhD
<div><h3>Introduction</h3><div>Hispanic and non-Hispanic Black (NHB) patients have worse OS compared to non-Hispanic White (NHW) patients and are less likely to utilize an unrelated HCT donor (PMID: 38661372, 39292462). PTCy reduces GvHD and allows for increased availability of alternative allogeneic donors in minority patients.</div></div><div><h3>Objectives</h3><div>In patients treated with PTCy, identify the best donor to maximize OS in a given race/ethnicity.</div></div><div><h3>Methods</h3><div>We performed a secondary analysis of adult patients (>19 yrs) who had a peripheral blood allogeneic HCT from 2013-2021 and received PTCy for GVHD prophylaxis using 3 publicly available datasets from CIBMTR. Donor age was available in 93% of patients. Kaplan-Meier curves estimated 2-year OS, and differences were compared using log-rank tests. X<sup>2</sup> tests helped identify potential confounders. Analyses were stratified by donor and self-reported race/ethnicity. The Cox Proportional Hazards model evaluated 2-year OS using a backwards elimination method to build the final prediction model.</div></div><div><h3>Results</h3><div>Of 5912 patients included, 70% were NHW, 16% were NHB, and 13% were Hispanic, with 58% Haploidentical (Haplo), 23% matched unrelated donor (MUD), 12% mismatched unrelated donor (MMUD), and 7% matched related donors (MRD).</div><div>Hispanic patients had significantly higher OS than NHW or NHB patients (P=0.009) and were younger (Aged 20-39 yrs: Hispanic 36%, NHW 14%, NHB 22%; P<0.0001). For NHW patients, patients transplanted with a MUD had higher OS than other donor sources (67 vs 58-60%; P=0.03). In contrast, NHB transplanted with MRD, Haplo, or MMUD had the highest OS compared to MUD, although this was not statistically significant (61-66% vs 42%; P=0.2). No difference existed in OS by donor source for Hispanic patients overall (P=0.9).</div><div>Accounting for donor age, NHB patients with a donor ≥30 yrs had the lowest OS with MUD compared to Haplo and MMUD patients (P=0.03 and 0.2, respectively, Figure 1B), but there was no OS difference with a donor <30 yrs (Figure 1A). NHW patients had superior OS with MUD vs Haplo if the donor was ≥30 yrs (P=0.0005, Figure 2B), but no OS difference between donor sources when the donor was <30 yrs (Figure 2A).</div><div>In Hispanic patients aged 20-39 yrs, mismatched donors (Haplo and MMUD) had higher OS compared to matched donors (MRD/MUD; P=0.03 and P=0.2, respectively, Figure 3A), whereas Hispanic patients aged 40-59 had lower OS with Haplo (P=0.1, Figure 3B), and aged 60+ had better OS with MRD/MUD than MMUD (Figure 3C).</div><div>After adjusting for significant factors associated with OS in multivariable analyses, stratified results race/ethnicity were similar to the univariate.</div></div><div><h3>Conclusion</h3><div>Mismatched donors had higher 2-year OS in NHB patients whose donor was ≥30 yrs old and Hispanic patients 20-39 yrs compared to matched donors. When select
与非西班牙裔白人（NHW）患者相比，西班牙裔和非西班牙裔黑人（NHB）患者的OS更差，并且不太可能使用无关的HCT供体（PMID: 38661372, 39292462）。PTCy减少GvHD，并允许少数患者增加其他异体供体的可用性。目的：在接受PTCy治疗的患者中，确定最佳供体以最大化给定种族/民族的OS。方法：我们对2013-2021年患有外周血异体HCT并接受PTCy预防GVHD的成人患者（19岁）进行了二次分析，使用了CIBMTR的3个公开数据集。93%的患者可获得供体年龄。Kaplan-Meier曲线估计2年OS，使用log-rank检验比较差异。X2检验有助于识别潜在的混杂因素。分析按供体和自我报告的种族/民族进行分层。Cox比例风险模型采用逆向消去法评估2年OS，建立最终预测模型。结果纳入的5912例患者中，70%为NHW， 16%为NHB， 13%为西班牙裔，其中单倍同型（Haplo）占58%，匹配非亲属供体（MUD）占23%，错配非亲属供体（MMUD）占12%，匹配亲属供体（MRD）占7%。西班牙裔患者的OS明显高于NHW或NHB患者（P=0.009），且年龄更年轻（20-39岁：西班牙裔36%，NHW 14%, NHB 22%; P<0.0001）。对于NHW患者，移植了MUD的患者的OS高于其他供体来源（67 vs 58-60%； P=0.03）。相比之下，MRD、Haplo或MMUD移植的NHB与MUD相比具有最高的OS，尽管这没有统计学意义（61-66% vs 42%； P=0.2）。西班牙裔患者的总体供体来源OS无差异（P=0.9）。考虑供者年龄，与Haplo和MMUD患者相比，供者年龄≥30岁的NHB患者与MUD的OS最低（P分别为0.03和0.2，图1B），但与供者年龄≥30岁的患者相比，OS无差异（图1A）。如果供体年龄≥30岁，NHW患者与Haplo相比，MUD的OS优于Haplo (P=0.0005，图2B)，但供体年龄≥30岁时，不同供体来源的OS无差异（图2A）。在20-39岁的西班牙裔患者中，错配供体（Haplo和MMUD）的OS高于匹配供体（MRD/MUD； P=0.03和P=0.2，分别，图3A），而40-59岁的西班牙裔患者Haplo的OS较低（P=0.1，图3B）， 60岁以上的患者MRD/MUD的OS优于MMUD（图3C）。在多变量分析中调整了与OS相关的重要因素后，分层结果种族/民族与单变量相似。结论供者年龄≥30岁的NHB患者和20 ~ 39岁的西班牙裔患者的2年OS高于匹配供者。在为HCT患者选择供体时，应考虑患者的种族/民族和年龄。
{"title":"In the Post-Transplant Cyclophosphamide (PTCy) Era, Overall Survival (OS) By Donor Differs By Recipient and Donor Age and Race/Ethnicity","authors":"Megan M. Herr PhD , Nisha M. Nair MS, MPH , Shernan Holtan MD , Nandita Khera MD, MPH , Theresa E. Hahn PhD","doi":"10.1016/j.jtct.2025.12.955","DOIUrl":"10.1016/j.jtct.2025.12.955","url":null,"abstract":"<div><h3>Introduction</h3><div>Hispanic and non-Hispanic Black (NHB) patients have worse OS compared to non-Hispanic White (NHW) patients and are less likely to utilize an unrelated HCT donor (PMID: 38661372, 39292462). PTCy reduces GvHD and allows for increased availability of alternative allogeneic donors in minority patients.</div></div><div><h3>Objectives</h3><div>In patients treated with PTCy, identify the best donor to maximize OS in a given race/ethnicity.</div></div><div><h3>Methods</h3><div>We performed a secondary analysis of adult patients (>19 yrs) who had a peripheral blood allogeneic HCT from 2013-2021 and received PTCy for GVHD prophylaxis using 3 publicly available datasets from CIBMTR. Donor age was available in 93% of patients. Kaplan-Meier curves estimated 2-year OS, and differences were compared using log-rank tests. X<sup>2</sup> tests helped identify potential confounders. Analyses were stratified by donor and self-reported race/ethnicity. The Cox Proportional Hazards model evaluated 2-year OS using a backwards elimination method to build the final prediction model.</div></div><div><h3>Results</h3><div>Of 5912 patients included, 70% were NHW, 16% were NHB, and 13% were Hispanic, with 58% Haploidentical (Haplo), 23% matched unrelated donor (MUD), 12% mismatched unrelated donor (MMUD), and 7% matched related donors (MRD).</div><div>Hispanic patients had significantly higher OS than NHW or NHB patients (P=0.009) and were younger (Aged 20-39 yrs: Hispanic 36%, NHW 14%, NHB 22%; P<0.0001). For NHW patients, patients transplanted with a MUD had higher OS than other donor sources (67 vs 58-60%; P=0.03). In contrast, NHB transplanted with MRD, Haplo, or MMUD had the highest OS compared to MUD, although this was not statistically significant (61-66% vs 42%; P=0.2). No difference existed in OS by donor source for Hispanic patients overall (P=0.9).</div><div>Accounting for donor age, NHB patients with a donor ≥30 yrs had the lowest OS with MUD compared to Haplo and MMUD patients (P=0.03 and 0.2, respectively, Figure 1B), but there was no OS difference with a donor <30 yrs (Figure 1A). NHW patients had superior OS with MUD vs Haplo if the donor was ≥30 yrs (P=0.0005, Figure 2B), but no OS difference between donor sources when the donor was <30 yrs (Figure 2A).</div><div>In Hispanic patients aged 20-39 yrs, mismatched donors (Haplo and MMUD) had higher OS compared to matched donors (MRD/MUD; P=0.03 and P=0.2, respectively, Figure 3A), whereas Hispanic patients aged 40-59 had lower OS with Haplo (P=0.1, Figure 3B), and aged 60+ had better OS with MRD/MUD than MMUD (Figure 3C).</div><div>After adjusting for significant factors associated with OS in multivariable analyses, stratified results race/ethnicity were similar to the univariate.</div></div><div><h3>Conclusion</h3><div>Mismatched donors had higher 2-year OS in NHB patients whose donor was ≥30 yrs old and Hispanic patients 20-39 yrs compared to matched donors. When select","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S76"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098484","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.2025.12.022
Joseph A. Pidala MD, PhD , Ryotaro Nakamura MD , George L. Chen MD , Ted A. Gooley PhD , Lynn Onstad MS , Julianne Dunlap MS , Geoffrey R Hill MD , Stephanie J. Lee MD, MPH
Preclinical studies (Koyama, Immunity 2019) have demonstrated that IL-12 is the critical cytokine driving alloantigen presentation in the gut and systemic acute GVHD following myeloablative conditioning (MAC). Donor Th1 and Th17 that mediate graft-vs.-host disease (GVHD) are IL-12 and IL-23 dependent. We previously demonstrated that Ustekinumab, an anti-IL-12/IL-23p40 neutralizing antibody, had biologic and clinical effects in an initial translational trial (Pidala, Haematologica 2018). To verify these findings, we conducted a multi-center, randomized, placebo-controlled, double-blinded phase II clinical trial to examine the efficacy of this approach (NCT04572815, drug support from J&J).
Included subjects were age 18-70 with hematologic malignancies, had 8/8 matched unrelated donors (MUD), PBSC grafts, myeloablative (MAC) or reduced-intensity conditioning (RIC), and adequate vital organ functioning. GVHD prevention included standard tacrolimus/methotrexate GVHD prophylaxis together with either Ustekinumab (IV induction dose 4-72 hours prior to start of HCT conditioning, then subcutaneous injection on days 50, 100 and 160 post-HCT) or matched placebo. The primary endpoint was 6-month grade II-IV acute GVHD-free survival (GFS). Odds ratios for failure for each endpoint were estimated with the Cochran-Mantel-Haenszel test, and 80% Clopper-Pearson confidence intervals were estimated.
A total of 116 patients were treated at four US centers (N=58 randomized to each study arm, stratified by study site and conditioning intensity), providing 81% power to observe a statistically significant (1-sided level of 10%) difference in 6-month GFS between groups. The majority had AML/ALL (62%), and conditioning included MAC in 48% or RIC in 52%. Median age was balanced (Ustekinumab 56 (range 21-69), placebo 58 (range 20-73)). The odds ratio (placebo vs. Ustekinumab) of failure for the primary endpoint 6-month GFS was 1.48 (80% CI, 0.91-2.4, one-sided p=0.15). Subgroup analysis demonstrated difference in 6-month GFS in the MAC treated patients (table). Additionally, secondary outcome measures supported benefit of Ustekinumab therapy: Day 100 GFS was improved, and non-relapse mortality (NRM) was reduced.
This randomized phase II trial aimed to determine whether there was sufficient evidence of benefit to pursue further investigation of this approach. While the primary 6-month GFS endpoint was not met, secondary outcomes suggest further study is warranted in the MAC setting.
{"title":"Randomized Phase II Trial of Ustekinumab for GVHD Prevention in Matched Unrelated Donor Transplants: Primary Trial Results","authors":"Joseph A. Pidala MD, PhD , Ryotaro Nakamura MD , George L. Chen MD , Ted A. Gooley PhD , Lynn Onstad MS , Julianne Dunlap MS , Geoffrey R Hill MD , Stephanie J. Lee MD, MPH","doi":"10.1016/j.jtct.2025.12.022","DOIUrl":"10.1016/j.jtct.2025.12.022","url":null,"abstract":"<div><div>Preclinical studies (<em>Koyama, Immunity 2019</em>) have demonstrated that IL-12 is the critical cytokine driving alloantigen presentation in the gut and systemic acute GVHD following myeloablative conditioning (MAC). Donor Th1 and Th17 that mediate graft-vs.-host disease (GVHD) are IL-12 and IL-23 dependent. We previously demonstrated that Ustekinumab, an anti-IL-12/IL-23p40 neutralizing antibody, had biologic and clinical effects in an initial translational trial (<em>Pidala, Haematologica 2018</em>). To verify these findings, we conducted a multi-center, randomized, placebo-controlled, double-blinded phase II clinical trial to examine the efficacy of this approach (NCT04572815, drug support from J&J).</div><div>Included subjects were age 18-70 with hematologic malignancies, had 8/8 matched unrelated donors (MUD), PBSC grafts, myeloablative (MAC) or reduced-intensity conditioning (RIC), and adequate vital organ functioning. GVHD prevention included standard tacrolimus/methotrexate GVHD prophylaxis together with either Ustekinumab (IV induction dose 4-72 hours prior to start of HCT conditioning, then subcutaneous injection on days 50, 100 and 160 post-HCT) or matched placebo. The primary endpoint was 6-month grade II-IV acute GVHD-free survival (GFS). Odds ratios for failure for each endpoint were estimated with the Cochran-Mantel-Haenszel test, and 80% Clopper-Pearson confidence intervals were estimated.</div><div>A total of 116 patients were treated at four US centers (N=58 randomized to each study arm, stratified by study site and conditioning intensity), providing 81% power to observe a statistically significant (1-sided level of 10%) difference in 6-month GFS between groups. The majority had AML/ALL (62%), and conditioning included MAC in 48% or RIC in 52%. Median age was balanced (Ustekinumab 56 (range 21-69), placebo 58 (range 20-73)). The odds ratio (placebo vs. Ustekinumab) of failure for the primary endpoint 6-month GFS was 1.48 (80% CI, 0.91-2.4, one-sided p=0.15). Subgroup analysis demonstrated difference in 6-month GFS in the MAC treated patients (<em>table</em>). Additionally, secondary outcome measures supported benefit of Ustekinumab therapy: Day 100 GFS was improved, and non-relapse mortality (NRM) was reduced.</div><div>This randomized phase II trial aimed to determine whether there was sufficient evidence of benefit to pursue further investigation of this approach. While the primary 6-month GFS endpoint was not met, secondary outcomes suggest further study is warranted in the MAC setting.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S7"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098506","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}
<div><h3>Background</h3><div>Sickle cell disease (SCD) is a debilitating inherited hemoglobinopathy causing progressive, age-dependent multi-organ damage. End-organ dysfunction, particularly of the liver and kidney, complicates curative therapy and leads to high morbidity and early mortality in young adults. Hematopoietic stem cell transplantation (HCT) remains the only established curative option, but transplantation-related risks often preclude its use in patients with severe comorbidities. Solid organ transplantation (SOT) corrects organ failure but does not treat underlying SCD. We report, for the first time, the feasibility, safety, and success of sequential SOT followed by non-myeloablative haploidentical HCT (haplo-HCT) from the same related donor in patients with severe SCD and advanced organ failure.</div></div><div><h3>Methods</h3><div>At King Faisal Specialist Hospital & Research Centre, four patients with homozygous SCD (3 with hepatic, 1 with renal dysfunction) underwent planned sequential living donor liver (LDLT, n=3) or kidney transplantation (LDKT, n=1), table 1, followed by haplo-HCT from the same haploidentical related donor. Non-myeloablative conditioning thiotepa based and post-transplant cyclophosphamide following the trial protocol NCT01850108, PMCID: PMC12356966 (Figure 1). Immunosuppression tapering began 12 months post-HCT, guided by donor chimerism and both grafts function.</div></div><div><h3>Results</h3><div>After a median follow-up of 37.5 months, all four patients (3 males, 1 female; median age 25 years) remain alive with stable SOT and HCT graft function. Median interval between SOT and HCT was 5.5 months. Median donor age was 30 years, CD34⁺ cell dose 5.24×10⁶/kg, and total nucleated cell dose 7.7×10⁷/kg. Full donor chimerism (≥95%) was achieved by day +30 in all but one patient, who maintained stable mixed chimerism (>90%). Median neutrophil and platelet engraftment occurred on days 21 and 33, respectively. No acute or chronic GvHD, graft rejection, or graft failure occurred. At one year post-HCT, hemoglobin S was 0% in three patients; the remaining patient (trait donor) had HbS 24%. All patients were successfully weaned off immunosuppression. Immune reconstitution was robust, with restoration of CD4+, CD8+, and NK cell subsets and ferritin levels improved, suggesting reversal of iron overload.</div></div><div><h3>Conclusion</h3><div>This is the first reported series of sequential liver or kidney transplantation followed by haplo-HCT from the same haploidentical donor in severe SCD. Our experience demonstrates the feasibility, safety, and curative potential of dual transplantation in patients with advanced SCD and related liver or kidney dysfunction. This approach allows for durable donor chimerism, organ graft function, and successful immunosuppression withdrawal through timmune tolerance induction. This strategy offers a curative platform for patients traditionally considered ineligible for HCT due to en
{"title":"Induction of Immune Tolerance after Haploidentical Stem Cell Transplantation Following Solid Organ Transplantation in Patients with Sickle Cell Disease","authors":"Ali Alahmari MD , Saad Alghamdi MD , Reem Alasbali MD , Manar Aleid MD , Hadeel Samarkandi PharmD , Hassan Aleid MD , Syed O Ahmed MD , Shaikha Alotaibi MD , Dieter Broering MD , Walid Rasheed MD , Mostafa Faisal Mohammed Mohammed Saleh MD , Abdulwahab Albabtain MD , Riad El Fakih MD , Sarah Samarkandi MD , Adetola A. Kassim MD , Hazzaa Alzahrani MD , Waleed Al-hamoudi MD , Mahmoud Aljurf MD , Fahad Almohareb MD","doi":"10.1016/j.jtct.2025.12.034","DOIUrl":"10.1016/j.jtct.2025.12.034","url":null,"abstract":"<div><h3>Background</h3><div>Sickle cell disease (SCD) is a debilitating inherited hemoglobinopathy causing progressive, age-dependent multi-organ damage. End-organ dysfunction, particularly of the liver and kidney, complicates curative therapy and leads to high morbidity and early mortality in young adults. Hematopoietic stem cell transplantation (HCT) remains the only established curative option, but transplantation-related risks often preclude its use in patients with severe comorbidities. Solid organ transplantation (SOT) corrects organ failure but does not treat underlying SCD. We report, for the first time, the feasibility, safety, and success of sequential SOT followed by non-myeloablative haploidentical HCT (haplo-HCT) from the same related donor in patients with severe SCD and advanced organ failure.</div></div><div><h3>Methods</h3><div>At King Faisal Specialist Hospital & Research Centre, four patients with homozygous SCD (3 with hepatic, 1 with renal dysfunction) underwent planned sequential living donor liver (LDLT, n=3) or kidney transplantation (LDKT, n=1), table 1, followed by haplo-HCT from the same haploidentical related donor. Non-myeloablative conditioning thiotepa based and post-transplant cyclophosphamide following the trial protocol NCT01850108, PMCID: PMC12356966 (Figure 1). Immunosuppression tapering began 12 months post-HCT, guided by donor chimerism and both grafts function.</div></div><div><h3>Results</h3><div>After a median follow-up of 37.5 months, all four patients (3 males, 1 female; median age 25 years) remain alive with stable SOT and HCT graft function. Median interval between SOT and HCT was 5.5 months. Median donor age was 30 years, CD34⁺ cell dose 5.24×10⁶/kg, and total nucleated cell dose 7.7×10⁷/kg. Full donor chimerism (≥95%) was achieved by day +30 in all but one patient, who maintained stable mixed chimerism (>90%). Median neutrophil and platelet engraftment occurred on days 21 and 33, respectively. No acute or chronic GvHD, graft rejection, or graft failure occurred. At one year post-HCT, hemoglobin S was 0% in three patients; the remaining patient (trait donor) had HbS 24%. All patients were successfully weaned off immunosuppression. Immune reconstitution was robust, with restoration of CD4+, CD8+, and NK cell subsets and ferritin levels improved, suggesting reversal of iron overload.</div></div><div><h3>Conclusion</h3><div>This is the first reported series of sequential liver or kidney transplantation followed by haplo-HCT from the same haploidentical donor in severe SCD. Our experience demonstrates the feasibility, safety, and curative potential of dual transplantation in patients with advanced SCD and related liver or kidney dysfunction. This approach allows for durable donor chimerism, organ graft function, and successful immunosuppression withdrawal through timmune tolerance induction. This strategy offers a curative platform for patients traditionally considered ineligible for HCT due to en","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S19"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098512","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.2025.12.036
Stephan A. Grupp MD, PhD , Michael S Grimley MD , Timothy Driscoll MD , Kris Michael Mahadeo MD MPH , Alexis Leonard MD , Yongping Wang MD PhD , Helen Phillips MD , David Justus MD , Leslie E. Lehmann MD , Erica Esrick MD , Sarah Nikiforow MD, PhD , Julie Kanter MD , Matthew Hsieh MD , John F. Tisdale MD , Akshay Sharma MBBS, MSc , Zachary D Crees MD , John Manis MD
The development and approval of gene therapies (GT) for sickle cell disease (SCD) and Beta-Thalassemia (TDT) has transformed treatment options for patients, however, a critical limitation remains in the ability to obtain sufficient autologous hematopoietic stem cells (HSCs) for ex vivo manufacture of a drug product. HSC mobilization for SCD is limited to single agent plerixafor (P), a CXCR4 antagonist, since G-CSF is associated with an increased risk of vaso-occlusive events (VOEs) and death. Many SCD and TDT patients require repeated collection cycles and sometimes fail to collect sufficient cells for manufacture. Motixafortide (M) is a long-acting CXCR4 inhibitor that is FDA approved in combination with G-CSF to mobilize HSCs for autologous transplant in multiple myeloma. These reported results prompted interest in using M to mobilize HSCs for people with SCD who had a poor response to P for GT, or in patients with TDT who failed to mobilize with G-CSF + P. In this context, we report the use of M at 5 centers in 11 patients, comprising 17 total collection cycles. Ages ranged from 14-50 years including 6 females. Each cycle incorporated ≥2 consecutive apheresis days. M (1.25 mg/kg) was given to patients with SCD 6-13 hours before apheresis in 11 cycles while in 4 cycles it was given only prior to the first session. Nine of 10 SCD patients obtained sufficient cells for manufacture; 1 patient failed to mobilize with either P or M. One patient with TDT was mobilized with G-CSF + M given 10 hours prior to each apheresis collection and obtained sufficient cells for manufacture.
The most common adverse events were induration at the injection site (94%), pruritis with rash or hives (89%), and local or generalized pain (62%, narcotics used in 41% of patients with SCD). There were 2 instances of lip swelling and fever, but no cases of anaphylaxis. Two patients required prolonged hospitalization for pain management, one attributed to VOE. To mitigate known local injection site and potential systemic reactions to M, all patients received prophylactic H-1 and H-2 antagonists and acetaminophen, with 86% receiving additional montelukast. Corticosteroids were used prophylactically in 27% and as treatment in 1 patient.
These results support further study and consideration of M for HSC mobilization in SCD or TDT and highlight its potential role for patients who fail to mobilize with standard therapies. Notably, currently approved GT products require nearly twice the number of HSCs for manufacture compared with the clinical trials, underscoring the urgent need for alternative mobilizing strategies to address this challenge. Ongoing clinical trials of M in SCD are examining safety, mobilization efficacy, optimal dose timing, and editing potential (NCT06442761; NCT05618301). Additional studies are warranted to determine the ideal timing with apheresis and prophylactic medication regimen.
{"title":"Improved Hematopoietic Stem Cell Mobilization for Gene Therapy of Hemoglobinopathies Using Single Agent Motixafortide","authors":"Stephan A. Grupp MD, PhD , Michael S Grimley MD , Timothy Driscoll MD , Kris Michael Mahadeo MD MPH , Alexis Leonard MD , Yongping Wang MD PhD , Helen Phillips MD , David Justus MD , Leslie E. Lehmann MD , Erica Esrick MD , Sarah Nikiforow MD, PhD , Julie Kanter MD , Matthew Hsieh MD , John F. Tisdale MD , Akshay Sharma MBBS, MSc , Zachary D Crees MD , John Manis MD","doi":"10.1016/j.jtct.2025.12.036","DOIUrl":"10.1016/j.jtct.2025.12.036","url":null,"abstract":"<div><div>The development and approval of gene therapies (GT) for sickle cell disease (SCD) and Beta-Thalassemia (TDT) has transformed treatment options for patients, however, a critical limitation remains in the ability to obtain sufficient autologous hematopoietic stem cells (HSCs) for <em>ex vivo</em> manufacture of a drug product. HSC mobilization for SCD is limited to single agent plerixafor (P), a CXCR4 antagonist, since G-CSF is associated with an increased risk of vaso-occlusive events (VOEs) and death. Many SCD and TDT patients require repeated collection cycles and sometimes fail to collect sufficient cells for manufacture. Motixafortide (M) is a long-acting CXCR4 inhibitor that is FDA approved in combination with G-CSF to mobilize HSCs for autologous transplant in multiple myeloma. These reported results prompted interest in using M to mobilize HSCs for people with SCD who had a poor response to P for GT, or in patients with TDT who failed to mobilize with G-CSF + P. In this context, we report the use of M at 5 centers in 11 patients, comprising 17 total collection cycles. Ages ranged from 14-50 years including 6 females. Each cycle incorporated ≥2 consecutive apheresis days. M (1.25 mg/kg) was given to patients with SCD 6-13 hours before apheresis in 11 cycles while in 4 cycles it was given only prior to the first session. Nine of 10 SCD patients obtained sufficient cells for manufacture; 1 patient failed to mobilize with either P or M. One patient with TDT was mobilized with G-CSF + M given 10 hours prior to each apheresis collection and obtained sufficient cells for manufacture.</div><div>The most common adverse events were induration at the injection site (94%), pruritis with rash or hives (89%), and local or generalized pain (62%, narcotics used in 41% of patients with SCD). There were 2 instances of lip swelling and fever, but no cases of anaphylaxis. Two patients required prolonged hospitalization for pain management, one attributed to VOE. To mitigate known local injection site and potential systemic reactions to M, all patients received prophylactic H-1 and H-2 antagonists and acetaminophen, with 86% receiving additional montelukast. Corticosteroids were used prophylactically in 27% and as treatment in 1 patient.</div><div>These results support further study and consideration of M for HSC mobilization in SCD or TDT and highlight its potential role for patients who fail to mobilize with standard therapies. Notably, currently approved GT products require nearly twice the number of HSCs for manufacture compared with the clinical trials, underscoring the urgent need for alternative mobilizing strategies to address this challenge. Ongoing clinical trials of M in SCD are examining safety, mobilization efficacy, optimal dose timing, and editing potential (NCT06442761; NCT05618301). Additional studies are warranted to determine the ideal timing with apheresis and prophylactic medication regimen.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S20-S21"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098514","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
Pediatric hematopoietic cell transplantation (HCT) and cellular therapy recipients, presenting to the emergency department (ED) with fever were experiencing intravenous (IV) antibiotic start times greater than 60 minutes from time of triage. Between July 2022 and March 2023, the first dose of antibiotic administration took, on average, 84.85 minutes. As research suggests, neutropenic pediatric oncology patients presenting to the ED with fever is a medical emergency requiring timely administration of antibiotics due to increased risk of morbidity, mortality, and increased health care costs (Wood, 2022). The recommended time for antibiotic administration is less than 60 minutes from presentation to the ED (Geerlinks, 2020).
This quality improvement project aimed at improving timely IV antibiotic administration for febrile neutropenic pediatric oncology patients including HCT and cellular therapy recipients presenting to the ED.
Methods, Intervention, & Analysis
A multidisciplinary team from the emergency, hematology/oncology (HemOnc), pharmacy, and informatic technology (IT) departments were created to assess gaps in practice, barriers, and mitigation strategies in April 2023. Multiple PDSA cycles from each department were implemented through July 2024. This included increasing clinical staff competence through education and creating a new infusaport validation process, improving prompt IV antibiotic ordering and delivery through IT and pharmacy process changes, and improving ED team communication and interdepartmental communication when patients arrive. Additionally, a new “On My Way” feature was created and implemented on the patient portal that enables patients to alert the ED when they are on their way.
Findings & Interpretation
From September 2024 through September 2025, IV antibiotic administration took, on average, 45.67 minutes from the time HCT and cellular therapy recipients were triaged in the ED, which is a decrease of 39.18 minutes.
Discussion & Implications
This improvement highlights the multidisciplinary collaboration across specialties which is key in managing these high-risk patients effectively. Additionally, improving timely IV antibiotic administration for this patient population is critical to improving patient outcomes.
主题意义&研究目的/背景/理由儿科造血细胞移植（HCT）和细胞治疗的受者，就诊于急诊科（ED）时出现发热，且静脉注射（IV）抗生素的起始时间从分诊时算起大于60分钟。在2022年7月至2023年3月期间，首次给药平均耗时84.85分钟。研究表明，中性粒细胞减少的儿科肿瘤患者在急诊科就诊时伴有发热，这是一种医疗紧急情况，由于发病率、死亡率和医疗费用的增加，需要及时给予抗生素治疗（Wood, 2022）。推荐的抗生素使用时间从就诊到急诊科少于60分钟（Geerlinks, 2020）。该质量改进项目旨在改善向急诊室就诊的发热性中性粒细胞减少儿童肿瘤患者（包括HCT患者和接受细胞治疗的患者）及时静脉注射抗生素的情况。方法、干预和分析由急诊科、血液科/肿瘤科（HemOnc）、药剂科和信息技术科（IT）组成的多学科团队于2023年4月成立，以评估实践中的差距、障碍和缓解策略。到2024年7月，每个部门都实施了多个PDSA周期。这包括通过教育和创建新的输液口验证流程来提高临床工作人员的能力，通过IT和药房流程的变化改善静脉抗生素的及时订购和交付，以及改善急诊科团队沟通和患者到达时的部门间沟通。此外，在患者门户网站上创建并实现了一个新的“On My Way”功能，使患者能够在他们正在路上时通知急诊科。从2024年9月到2025年9月，静脉抗生素给药时间从HCT和细胞治疗患者在急诊科分类的时间平均为45.67分钟，减少了39.18分钟。讨论&启示这一改进突出了跨专业的多学科合作，这是有效管理这些高危患者的关键。此外，改善及时静脉注射抗生素对改善患者预后至关重要。
{"title":"Improving First Dose Antibiotic Times for Febrile Transplant and Cellular Therapy Patients Presenting to the Emergency Department","authors":"Kathleen Lee BA, MSN, RN, CPN, CPHON , Robyn Abernathy MSN, RN, CNL, CPHON , Mistie Cook MNSc, CPN, CPHON , Karly Brooks BSN, RN, CPHON , Kris Dunlap PharmD, MSPhm, BSE , Mikayla Crosby BSN, RN , Vickie Hutchison BSN, RN, CPEN, SANE-P , Shelby Moore BSN, RN, CPEN , Emily Rader MSN, RN, CPN , Melissa Easdon MBA, BSN, BA, RN","doi":"10.1016/j.jtct.2025.12.112","DOIUrl":"10.1016/j.jtct.2025.12.112","url":null,"abstract":"<div><h3>Topic Significance & Study Purpose/Background/Rationale</h3><div>Pediatric hematopoietic cell transplantation (HCT) and cellular therapy recipients, presenting to the emergency department (ED) with fever were experiencing intravenous (IV) antibiotic start times greater than 60 minutes from time of triage. Between July 2022 and March 2023, the first dose of antibiotic administration took, on average, 84.85 minutes. As research suggests, neutropenic pediatric oncology patients presenting to the ED with fever is a medical emergency requiring timely administration of antibiotics due to increased risk of morbidity, mortality, and increased health care costs (Wood, 2022). The recommended time for antibiotic administration is less than 60 minutes from presentation to the ED (Geerlinks, 2020).</div><div>This quality improvement project aimed at improving timely IV antibiotic administration for febrile neutropenic pediatric oncology patients including HCT and cellular therapy recipients presenting to the ED.</div></div><div><h3>Methods, Intervention, & Analysis</h3><div>A multidisciplinary team from the emergency, hematology/oncology (HemOnc), pharmacy, and informatic technology (IT) departments were created to assess gaps in practice, barriers, and mitigation strategies in April 2023. Multiple PDSA cycles from each department were implemented through July 2024. This included increasing clinical staff competence through education and creating a new infusaport validation process, improving prompt IV antibiotic ordering and delivery through IT and pharmacy process changes, and improving ED team communication and interdepartmental communication when patients arrive. Additionally, a new “On My Way” feature was created and implemented on the patient portal that enables patients to alert the ED when they are on their way.</div></div><div><h3>Findings & Interpretation</h3><div>From September 2024 through September 2025, IV antibiotic administration took, on average, 45.67 minutes from the time HCT and cellular therapy recipients were triaged in the ED, which is a decrease of 39.18 minutes.</div></div><div><h3>Discussion & Implications</h3><div>This improvement highlights the multidisciplinary collaboration across specialties which is key in managing these high-risk patients effectively. Additionally, improving timely IV antibiotic administration for this patient population is critical to improving patient outcomes.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S80-S81"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098516","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.2025.12.044
Warren B. Fingrut MD , KaNoisha Codrington , Denai R. Milton MS , Ligny Hunter , Ricky Garcia , Charles S Martinez BS , Gabriela Rondon MD , Christopher R. Flowers MD , Elizabeth J. Shpall MD
<div><h3>Background</h3><div>Although patient (pt) social/financial barriers impact transplant (BMT) outcomes, comprehensive, granular social determinants of health (SDOH) data are not routinely collected across our field.</div></div><div><h3>Objective</h3><div>We launched a single center, prospective, observational cohort study to determine BMT pts’ social/financial barriers to care (clinicaltrials.gov NCT06431347).</div></div><div><h3>Methods</h3><div>Pts were eligible if ≥18 years & received BMT financial approval. The study opened 7/2024 to allograft & 11/2024 to autograft pts. A dedicated staff member recorded detailed SDOH data, after explaining why these data were needed. Pts reporting urgent financial needs were offered social work referral. We examined multiple social (low pt/caregiver educational attainment/ English language level or low pt confidence with written medical information) & financial [household income below median of our city ($60,000), cost-of-living/ medical expense insecurity, or high-risk of financial toxicity by COST-FACIT score ≤24] barriers by pt ancestry & graft source.</div></div><div><h3>Results</h3><div>From 7/1/24-10/2/25, 496 pts were screened for the study & most (473/497, 95%) enrolled; 10 (2%) died prior to enrollment & only 13 (3%) declined to participate. Of 473 enrolled pts [median age 62 yrs, range 19-82; 283 (60%) with acute leukemia/MDS/MPN; 315 European & 158 non-European ancestry], most (466, 99%) enrolled ±45 days from BMT. 148 received auto- & 325 allografts [37 (11%) HLA-mismatched]. In a sub-analysis exploring data collection acceptability, most participants felt the data collection process was comfortable & low effort.</div><div>Overall, 62 (13%) pts reported ≥1 social barrier & 203 (43%) pts reported ≥1 financial barrier (Fig 1A). By ancestry, compared with Europeans, non-European pts had greater social & financial vulnerability, with >2x the proportion having ≥1 or ≥2 social barriers & >2x with ≥2 financial barriers (all p<0.001, Fig 1B). By graft source, similar proportions of auto & allograft pts faced social & financial barriers. Importantly, different SDOH measures classified different subsets of pts as vulnerable (Fig 2).</div><div>Overall, 89 (19%) pts reported urgent financial needs, with 61 (13%) referred to social work & 44 (9%) receiving grant support &/or financial/resource counseling.</div></div><div><h3>Conclusions</h3><div>We describe detailed SDOH data for pts across a department at a large cancer center & show the data collection process to be feasible & acceptable to pts with a very high participation rate. We demonstrate the application of these data to health outcomes research (ie highlighting non-European transplant recipients face high social & financial needs) & to pt care (ie supporting identification & addressing of urgent pt social/financial needs). Our work will support standa
{"title":"Prospective Observational cohort study to Collect Granular Social Determinants of Health Data for Hematopoietic Cell Transplant Patients","authors":"Warren B. Fingrut MD , KaNoisha Codrington , Denai R. Milton MS , Ligny Hunter , Ricky Garcia , Charles S Martinez BS , Gabriela Rondon MD , Christopher R. Flowers MD , Elizabeth J. Shpall MD","doi":"10.1016/j.jtct.2025.12.044","DOIUrl":"10.1016/j.jtct.2025.12.044","url":null,"abstract":"<div><h3>Background</h3><div>Although patient (pt) social/financial barriers impact transplant (BMT) outcomes, comprehensive, granular social determinants of health (SDOH) data are not routinely collected across our field.</div></div><div><h3>Objective</h3><div>We launched a single center, prospective, observational cohort study to determine BMT pts’ social/financial barriers to care (clinicaltrials.gov NCT06431347).</div></div><div><h3>Methods</h3><div>Pts were eligible if ≥18 years & received BMT financial approval. The study opened 7/2024 to allograft & 11/2024 to autograft pts. A dedicated staff member recorded detailed SDOH data, after explaining why these data were needed. Pts reporting urgent financial needs were offered social work referral. We examined multiple social (low pt/caregiver educational attainment/ English language level or low pt confidence with written medical information) & financial [household income below median of our city ($60,000), cost-of-living/ medical expense insecurity, or high-risk of financial toxicity by COST-FACIT score ≤24] barriers by pt ancestry & graft source.</div></div><div><h3>Results</h3><div>From 7/1/24-10/2/25, 496 pts were screened for the study & most (473/497, 95%) enrolled; 10 (2%) died prior to enrollment & only 13 (3%) declined to participate. Of 473 enrolled pts [median age 62 yrs, range 19-82; 283 (60%) with acute leukemia/MDS/MPN; 315 European & 158 non-European ancestry], most (466, 99%) enrolled ±45 days from BMT. 148 received auto- & 325 allografts [37 (11%) HLA-mismatched]. In a sub-analysis exploring data collection acceptability, most participants felt the data collection process was comfortable & low effort.</div><div>Overall, 62 (13%) pts reported ≥1 social barrier & 203 (43%) pts reported ≥1 financial barrier (Fig 1A). By ancestry, compared with Europeans, non-European pts had greater social & financial vulnerability, with >2x the proportion having ≥1 or ≥2 social barriers & >2x with ≥2 financial barriers (all p<0.001, Fig 1B). By graft source, similar proportions of auto & allograft pts faced social & financial barriers. Importantly, different SDOH measures classified different subsets of pts as vulnerable (Fig 2).</div><div>Overall, 89 (19%) pts reported urgent financial needs, with 61 (13%) referred to social work & 44 (9%) receiving grant support &/or financial/resource counseling.</div></div><div><h3>Conclusions</h3><div>We describe detailed SDOH data for pts across a department at a large cancer center & show the data collection process to be feasible & acceptable to pts with a very high participation rate. We demonstrate the application of these data to health outcomes research (ie highlighting non-European transplant recipients face high social & financial needs) & to pt care (ie supporting identification & addressing of urgent pt social/financial needs). Our work will support standa","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S25-S26"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098558","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.2025.12.050
Claire Roddie MD , Jae H Park MD , Eleni Tholouli MD , Karamjeet S. Sandhu MD , Paul Shaughnessy MD , Pere Barba MD , Manuel Guerreiro MD , Deborah Yallop MD , Aaron C Logan MD , Mehrdad Abedi MD , Pierre Lao-Sirieix Ph.D. , Ping Wang PhD , Wolfram Brugger MD , Bijal D Shah MD , Michael R Bishop MD , Daniel J DeAngelo MD, PhD , Elias Jabbour MD
<div><h3>Introduction</h3><div>Obe-cel, an autologous anti-CD19 CAR T-cell therapy, showed clinical efficacy in adult pts with R/R B-ALL in the Phase Ib/II FELIX study (NCT04404660; Roddie C, et al. NEJM 2024). Complete remission (CR)/CR with incomplete hematologic recovery (CRi) was achieved in 78.0% pts; 24-month (mo) event-free survival (EFS) and overall survival (OS) probabilities were 43.0% and 46.0%, respectively. Previously, multivariate analysis identified CAR T-cell persistence as an important predictive factor for EFS and OS following obe-cel infusion (Park JH, et al. EHA 2025).</div></div><div><h3>Objective</h3><div>To evaluate the impact of persistence status at M3 on survival outcomes in adults with R/R B-ALL who responded to obe-cel.</div></div><div><h3>Methods</h3><div>In FELIX, pts (≥18 years) with R/R B-ALL received lymphodepletion prior to tumor burden-guided obe-cel infusions (total target dose: 410×10<sup>6</sup> CAR T-cells). Droplet digital polymerase chain reaction measured CAR transgene levels in the peripheral blood of pts infused with ≥1 dose of obe-cel (N=127). Vector copy number per diploid genome was determined by duplex detection of the lentiviral vector Ψ region and the endogenous reference gene <em>RPP30</em>. Samples with measurements above the lower limit of detection (LLoD; 11 copies/reaction) were identified as CAR T-cell positive; measurements below the LLoD indicated loss of CAR T-cell persistence. M3 landmark Kaplan-Meier analysis was used to evaluate EFS and OS by persistence status (ongoing vs loss) in pts who responded to obe-cel and were in ongoing remission beyond M3, and in pts with deep measurable residual disease (MRD)-negative remission (<10<sup>–6</sup> leukemic cells) who did not receive post obe-cel stem cell transplant (SCT).</div></div><div><h3>Results</h3><div>As of January 18, 2025, (median follow up: 32.8 mos; range: 19.9–52.8 mos) 99 pts achieved CR/CRi and 79/99 pts (79.8%) had ongoing remission beyond M3 post obe-cel infusion. At M3, 60/79 pts (75.9%) had ongoing CAR T-cell persistence, while 19/79 (24.1%) had lost persistence (<strong>Table 1</strong>). Median EFS and 24-mos EFS/OS probabilities were longer in pts with ongoing persistence at M3, than in pts who had lost persistence (<strong>Table 1; Figure 1A</strong>). Of the pts with ongoing remission at M3, 70/79 (88.6%) did not receive post obe-cel SCT. The median EFS/OS and 24-mos probabilities in these 70 pts, by persistence status at M3, aligned with those reported in the 79 pts with ongoing remission (<strong>Table 1; Figure 1B</strong>). Of the pts with no post obe-cel SCT, 54/70 (77.1%) had next-generation sequencing calibration and 49/54 pts (90.7%) achieved deep MRD-negative remission by M3 (<strong>Table 1</strong>).</div></div><div><h3>Conclusions</h3><div>In pts who remained in remission beyond M3 (including pts with deep MRD-negative remission and no post obe-cel SCT), ongoing CAR T-cell persistence at M3 was associate
{"title":"Chimeric Antigen Receptor (CAR) T-cell Persistence at Month 3 (M3) Predicts Clinical Outcomes in Adult Patients (pts) with Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (R/R B-ALL) Treated with Obecabtagene autoleucel (obe-cel)","authors":"Claire Roddie MD , Jae H Park MD , Eleni Tholouli MD , Karamjeet S. Sandhu MD , Paul Shaughnessy MD , Pere Barba MD , Manuel Guerreiro MD , Deborah Yallop MD , Aaron C Logan MD , Mehrdad Abedi MD , Pierre Lao-Sirieix Ph.D. , Ping Wang PhD , Wolfram Brugger MD , Bijal D Shah MD , Michael R Bishop MD , Daniel J DeAngelo MD, PhD , Elias Jabbour MD","doi":"10.1016/j.jtct.2025.12.050","DOIUrl":"10.1016/j.jtct.2025.12.050","url":null,"abstract":"<div><h3>Introduction</h3><div>Obe-cel, an autologous anti-CD19 CAR T-cell therapy, showed clinical efficacy in adult pts with R/R B-ALL in the Phase Ib/II FELIX study (NCT04404660; Roddie C, et al. NEJM 2024). Complete remission (CR)/CR with incomplete hematologic recovery (CRi) was achieved in 78.0% pts; 24-month (mo) event-free survival (EFS) and overall survival (OS) probabilities were 43.0% and 46.0%, respectively. Previously, multivariate analysis identified CAR T-cell persistence as an important predictive factor for EFS and OS following obe-cel infusion (Park JH, et al. EHA 2025).</div></div><div><h3>Objective</h3><div>To evaluate the impact of persistence status at M3 on survival outcomes in adults with R/R B-ALL who responded to obe-cel.</div></div><div><h3>Methods</h3><div>In FELIX, pts (≥18 years) with R/R B-ALL received lymphodepletion prior to tumor burden-guided obe-cel infusions (total target dose: 410×10<sup>6</sup> CAR T-cells). Droplet digital polymerase chain reaction measured CAR transgene levels in the peripheral blood of pts infused with ≥1 dose of obe-cel (N=127). Vector copy number per diploid genome was determined by duplex detection of the lentiviral vector Ψ region and the endogenous reference gene <em>RPP30</em>. Samples with measurements above the lower limit of detection (LLoD; 11 copies/reaction) were identified as CAR T-cell positive; measurements below the LLoD indicated loss of CAR T-cell persistence. M3 landmark Kaplan-Meier analysis was used to evaluate EFS and OS by persistence status (ongoing vs loss) in pts who responded to obe-cel and were in ongoing remission beyond M3, and in pts with deep measurable residual disease (MRD)-negative remission (<10<sup>–6</sup> leukemic cells) who did not receive post obe-cel stem cell transplant (SCT).</div></div><div><h3>Results</h3><div>As of January 18, 2025, (median follow up: 32.8 mos; range: 19.9–52.8 mos) 99 pts achieved CR/CRi and 79/99 pts (79.8%) had ongoing remission beyond M3 post obe-cel infusion. At M3, 60/79 pts (75.9%) had ongoing CAR T-cell persistence, while 19/79 (24.1%) had lost persistence (<strong>Table 1</strong>). Median EFS and 24-mos EFS/OS probabilities were longer in pts with ongoing persistence at M3, than in pts who had lost persistence (<strong>Table 1; Figure 1A</strong>). Of the pts with ongoing remission at M3, 70/79 (88.6%) did not receive post obe-cel SCT. The median EFS/OS and 24-mos probabilities in these 70 pts, by persistence status at M3, aligned with those reported in the 79 pts with ongoing remission (<strong>Table 1; Figure 1B</strong>). Of the pts with no post obe-cel SCT, 54/70 (77.1%) had next-generation sequencing calibration and 49/54 pts (90.7%) achieved deep MRD-negative remission by M3 (<strong>Table 1</strong>).</div></div><div><h3>Conclusions</h3><div>In pts who remained in remission beyond M3 (including pts with deep MRD-negative remission and no post obe-cel SCT), ongoing CAR T-cell persistence at M3 was associate","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S30-S31"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098563","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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