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Effect of Inflammatory Bowel Disease on Clinical Outcomes of Hematopoietic Cell Transplantation for Inborn Errors of Immunity 炎性肠病对先天性免疫缺陷患者造血细胞移植临床疗效的影响。
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2025.11.006
Ryu Yanagisawa , Satoshi Miyamoto , Yoji Sasahara , Michiko Kajiwara , Masataka Ishimura , Hirotoshi Sakaguchi , Takehiko Doi , Yoshiyuki Takahashi , Yuko Cho , Maho Sato , Saori Katayama , Katsuyoshi Koh , Masakatsu Yanagimachi , Daiichiro Hasegawa , Keiko Okada , Junko Takita , Shoji Saito , Atsushi Sato , Moeko Hino , Kimikazu Matsumoto , Katsutsugu Umeda
Inflammatory bowel disease (IBD) is a phenotype of patients with inborn errors of immunity (IEI). Allogeneic hematopoietic cell transplantation (HCT) is an established curative treatment for IEI; however, the effect of IBD on HCT outcomes is unclear. We evaluated the impact of IBD on post-HCT prognosis in pediatric patients with IEI. We used the Japanese transplant registry database to retrospectively analyze the medical records of 625 patients with pediatric IEI who underwent allogeneic HCT between 2007 and 2022 to evaluate the clinical impact of IBD on these patients. Sixty-six (10.6%) patients had concurrent IBD before HCT. Compared with patients without IBD, those with IBD did not show inferior overall survival, transplant-related mortality, or neutrophil and platelet engraftment. Moreover, no significant differences were observed in the incidence of acute or chronic graft-versus-host disease (GVHD) between the two groups. However, the IBD group had a higher incidence of acute gastrointestinal GVHD. These findings remained consistent even after propensity score matching, accounting for the identified risk factors, including age at HCT, performance status, total HCT-specific comorbidity index score, HLA mismatch, era of HCT, and underlying disease classification. IBD has a limited effect on HCT outcomes in patients with pediatric IEI, despite the higher incidence of acute gastrointestinal GVHD. Nevertheless, in this study, we included patients with heterogeneous and complex disease backgrounds, indicating the need for further investigation to confirm the findings.
背景:炎症性肠病(IBD)是先天性免疫缺陷(IEI)患者的一种表型。同种异体造血细胞移植(HCT)是治疗IEI的有效方法;然而,IBD对HCT结果的影响尚不清楚。目的:我们评估IBD对IEI患儿hct后预后的影响。研究设计:我们使用日本移植登记数据库,回顾性分析2007年至2022年间625例接受同种异体HCT的儿童IEI患者的医疗记录,以评估IBD对这些患者的临床影响。结果:66例(10.6%)患者在HCT前并发IBD。与没有IBD的患者相比,IBD患者没有表现出较差的总生存率、移植相关死亡率(TRM)或中性粒细胞和血小板植入。此外,两组间急性或慢性移植物抗宿主病(GVHD)的发生率无显著差异。然而,IBD组急性胃肠道GVHD的发生率更高。即使在倾向评分匹配后,这些发现仍然一致,考虑到确定的危险因素,包括HCT年龄、运动状态、HCT特异性共病指数总分、HLA错配、HCT时代和潜在疾病分类。结论:尽管急性胃肠道GVHD的发生率较高,但IBD对儿童IEI患者HCT结果的影响有限。然而,在这项研究中,我们纳入了异质性和复杂疾病背景的患者,这表明需要进一步的调查来证实这些发现。
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引用次数: 0
Real-World Outcome of Defibrotide Treatment for Severe Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation 去纤维肽治疗造血细胞移植后严重肝脏VOD/SOS的实际治疗效果。
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2025.10.003
Jae-Ho Yoon, Daehun Kwag, Gi June Min, Sung-Soo Park, Silvia Park, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication following hematopoietic cell transplantation (HCT), with a markedly poor prognosis in patients with severe or very severe presentations. Defibrotide (DF) is the sole approved treatment for severe to very severe VOD/SOS, but real-world evidence remains limited, particularly in East Asian populations. We retrospectively analyzed 73 adult patients with severe or very severe VOD/SOS treated with DF between 2016 and 2023 at a single tertiary center in Korea. Diagnosis and grading were based on the revised European Society for Blood and Marrow Transplantation criteria. During the study period, national reimbursement guidelines for DF evolved from requiring ≥4 of 6 severity criteria to ≥2 of 5 severity criteria, allowing earlier initiation of treatment. The median time from HCT to diagnosis of VOD/SOS was 24 days (range, 1 to 843 days), and DF was administered within a median of 1 day after diagnosis. At DF initiation, 40 patients were classified as severe and 33 were classified as very severe; disease progression resulted in 53 patients reaching the very severe category. The overall response rate was 46.5%, and complete resolution was achieved in 39.7% of cases. The 100-day overall survival was 34.2%, significantly higher in the patients receiving DF within 2 days of diagnosis (36.0% versus 17.4%; P = .049). High total bilirubin levels at diagnosis and at the worst disease period were strongly associated with poor long-term survival regardless of severity criteria. These data provide real-world support for the early use of DF and suggest the prognostic utility of total bilirubin level in guiding treatment for VOD/SOS following HCT.
肝静脉闭塞性疾病/静脉窦阻塞综合征(VOD/SOS)是造血细胞移植(HCT)后的严重并发症,严重或极严重的患者预后明显差。去纤肽(DF)是唯一被批准的治疗严重至极严重VOD/SOS的方法,但现实证据仍然有限,特别是在东亚人群中。我们回顾性分析了2016年至2023年在韩国一个三级医疗中心接受DF治疗的73例严重或极严重VOD/SOS成年患者。诊断和分级基于修订后的EBMT标准。在研究期间,国家DF报销指南从要求6项严重性标准中的≥4项发展到要求5项严重性标准中的≥2项,从而允许更早开始治疗。从HCT到VOD/SOS诊断的中位时间为24天(范围从D-1到D+843), DF在诊断后的中位时间为1天。在DF开始时,40例患者被分类为严重,33例为非常严重;疾病进展导致53名患者达到非常严重的级别。总有效率为46.5%,完全缓解率为39.7%。100天总生存率(OS)为34.2%,在诊断2天内接受DF的患者中显着更高(36.0%比17.4%,p=0.049)。无论严重程度标准如何,诊断时和疾病最严重时期的高总胆红素水平与较差的长期生存率密切相关。这些数据为早期使用DF提供了现实支持,并提示胆红素水平在指导HCT后VOD/SOS治疗中的预后效用。
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引用次数: 0
Herpes Zoster Frequency and Adjuvanted Recombinant Zoster Vaccination after Allogeneic Hematopoietic Cell Transplantation 异体造血细胞移植后的带状疱疹发病率和佐剂重组带状疱疹疫苗接种。
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2025.10.028
Victoria G. Hall , Caden Chiarello , Mats Remberger , Deepali Kumar , Ivan Pasic , Dennis Dong Hwan Kim , Rajat Kumar , Auro Viswabandya , Fotios V. Michelis , Arjun Law , Armin Gerbitz , Sapna Humar , Wilson Lam , Igor Novitzky-Basso , Jonas Mattsson
<div><div>The prevention of herpes zoster (HZ) is of prime importance in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). Shingrix, an inactivated, adjuvanted recombinant zoster vaccine (aRZV), is now available and recommended for preventing HZ in seropositive immunocompromised patients. The safety and efficacy of this vaccine have been established in autologous HCT (autoHCT) recipients and other immunocompromised patients; however, data on alloHCT recipients are limited. The primary outcome of this study was a comparison of HZ frequency in alloHCT recipients who received aRZV vaccination and those who did not. Other characteristics of interest include the clinical presentation of HZ, treatment, and outcomes related to the HZ episode. This single-center retrospective observational cohort study was conducted at Princess Margaret Hospital, Toronto, Canada between April 1, 2018, and May 1, 2024. Adult patients who underwent alloHCT between April 1 2018, and December 31, 2022, were included in a prospective registry. Follow-up was censored at time of death, at 90 days after the first episode of HZ, at loss to follow-up, at the end of the study period, or 36 months post-alloHCT. Data were collected systematically from the electronic medical record or registry. A confirmed HZ episode was defined by clinical and/or molecular criteria. Statistical analysis was performed to determine risk factors associated with HZ and the relative risk (RR) of HZ episodes occurring in those ≥12 months post-alloHCT considering aRZV status and the cumulative follow-up period. A total of 445 patients were included. The median age was 56 years (interquartile range [IQR], 38 to 64 years), with a slight male predominance (n = 241/445; 54.2%). From ≥12 months post-alloHCT, there were 43 HZ episodes, including 26 of 263 patients (9.9%) who had received at least 1 dose of aRZV, 19 of 263 (7.2%) who had received 2 doses, 7 of 70 (10.0%) who did not receive RZV, and 10 of 112 (8.9%) with unknown vaccination status. The median time to HZ after receipt of any dose of aRZV was 8.1 months (IQR, 3.9 to 12.3 months). Overall, the median time to first HZ episode post-alloHCT was 20.7 months (IQR, 16.9 to 27.9 months), and the majority of HZ episodes occurred after cessation of antiviral prophylaxis (n = 38 of 43; 88.4%). Most HZ episodes were localized (n = 38; 88.4%) and treated in the outpatient setting with oral antiviral therapy (n = 39; 90.7%) for a median of 10 days (IQR, 7 to 14 days). Disseminated HZ did not occur in any aRZV recipients. Considering aRZV status and follow-up period, the RR of HZ in those who had received 2 doses of aRZV compared to those who had not received any doses of aRZV was 0.90 (95% confidence interval, 0.75 to 1.07; <em>P</em> = .22). In a sensitivity analysis, the risk of HZ was reduced (lower RR) in those receiving aRZV ≥12 months post-alloHCT compared with those who did not receive aRZV. Overall, the receipt of aRZV did not a
背景:预防带状疱疹(HZ)对异体造血细胞移植(alloHCT)后的患者至关重要。Shingrix是一种灭活佐剂重组带状疱疹疫苗(aRZV),目前已上市,推荐用于预防血清阳性免疫功能低下患者的HZ。该疫苗在自体HCT和其他免疫功能低下患者中的安全性和有效性已经确定,然而,对于同种异体HCT接受者,数据有限。目的:主要结果是接受aRZV疫苗接种的患者与未接受aRZV疫苗接种的患者在同种异体hct后发生HZ的频率。其他感兴趣的特征包括HZ的临床表现、治疗和与HZ发作相关的结果。研究设计:2018年4月1日至2024年5月1日,在加拿大多伦多玛格丽特公主医院进行了一项单中心回顾性观察队列研究。在2018年4月1日至2022年12月31日期间接受同种异体hct治疗的成年患者纳入前瞻性登记。随访在死亡时、首次HZ发作后90天、随访失败、研究期结束或同种hct后36个月时停止。系统地从电子病历或登记中收集数据。确认的HZ发作由临床和/或分子标准定义。考虑aRZV状态和累计随访时间,进行统计学分析以确定与HZ相关的危险因素以及HCT后≥12个月发生HZ发作的相对风险(RR)。结果:共纳入445例患者。年龄中位数为56岁(四分位数范围,IQR, 38 ~ 64),男性占轻微优势(241/445,54.2%)。从同种异体hct后≥12个月开始,发生了43次HZ发作,其中至少接受过一剂aRZV的患者中有26/263(9.9%),接受过两次aRZV的患者中有19/263(7.2%),未接受aRZV的患者中有7/70(10.0%),接种状况未知的患者中有10/112(8.9%)。任何剂量aRZV后至HZ的中位时间为8.1个月(IQR为3.9 - 12.3)。总体而言,异位hct后到HZ发作的中位时间为20.7个月(IQR为16.9 - 27.9),大多数发生在停止抗病毒预防治疗后(38/43,88.4%)。大多数HZ发作是局部的(38/43,88.4%),在门诊接受口服抗病毒治疗(39/43,90.7%),中位时间为10天(IQR 7 -14)。aRZV感染者无播散性HZ。考虑到aRZV状态和随访期,接受过两剂aRZV的患者与未接受任何剂量aRZV的患者相比,HZ的RR为0.90(95%置信区间0.75-1.07,p = 0.22)。在一项敏感性分析中,与未接受aRZV的患者相比,在hct后接受aRZV≥12个月的患者发生HZ的风险降低(较低的RR)。结论:总体而言,接受aRZV似乎并不影响同种异体HCT后患者HZ的频率,然而,如果在HCT后接受超过12个月的aRZV治疗,可能会有疾病严重程度的改变和获益。我们提供的初步发现将受益于前瞻性随机试验的进一步评估。
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引用次数: 0
Excellent Outcome of 1-Day Nonmyeloablative Salvage Regimen for Pediatric Patients with Graft Failure following Haploidentical Hematopoietic Stem Cell Transplantation 单倍同型造血干细胞移植后移植失败的儿童患者的1天非清髓挽救方案的良好结果。
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2025.10.030
Wilson Y.K. Chan , Pamela P.W. Lee , Daniel K.L. Cheuk , Wing Leung
<div><div>Haploidentical (haplo-) hematopoietic stem cell transplantation (HSCT) has been increasingly used as an alternative transplantation strategy for patients lacking a suitable HLA-matched donor. T cell depletion reduces the risk of graft-versus-host disease (GVHD) but at a cost of increased risk of graft failure, necessitating immediate retransplantation if a cryopreserved autologous graft is not available for rescue. Traditional high-intensity reconditioning with myeloablative and immunoablative regimens of approximately 1 week’s duration aimed at further suppressing the recipient-derived immune system capable of rejecting the primary graft, is associated with high morbidity and mortality. A shortened and reduced-intensity conditioning regimen might reduce infection risk and mortality, but sustained engraftment would be a concern with lowered intensity. Here we report the excellent outcomes of 11 pediatric patients who received a 1-day reduced-intensity preparative regimen prior to retransplantation for graft failure following initial myeloablative haplo-HSCT for various malignant and nonmalignant disease conditions. This was a retrospective study conducted at the Hong Kong Children’s Hospital, the sole territory-wide pediatric HSCT center in Hong Kong. All pediatric patients who were age ≤18 years at the time of initial haplo-HSCT and subsequently underwent salvage haplo-HSCT with a 1-day nonmyeloablative salvage regimen owing to graft failure between June 1, 2021, and May 31, 2024, were included. The salvage regimen consisted of fludarabine (30 mg/m<sup>2</sup>), cyclophosphamide (2000 mg/m<sup>2</sup> or 60 mg/kg), and alemtuzumab (0.3 mg/kg), with or without total body irradiation (2 Gy), all administered 1 day before retransplantation. G-CSF-mobilized peripheral blood stem cells (PBSCs) were collected and transplanted fresh without ex vivo T cell depletion whenever possible, while cryopreserved PBSCs were used if fresh apheresis was not possible. GVHD prophylaxis consisted of cyclosporine, mycophenolate mofetil, tacrolimus, or sirolimus. A total of 11 patients were recruited, including 9 males and 2 females, with a median age of 8.8 years (range, 2.4 to 17.5 years). Underlying diseases included transfusion-dependent anemias (n = 7; beta-thalassemia major = 4, hemoglobin Hammersmith = 1, pyruvate kinase deficiency = 1, severe aplastic anemia = 1), chronic granulomatous disease (n = 1), acute lymphoblastic leukemia (n = 1), post-liver transplant lymphoproliferative disease (n = 1) and neuroblastoma (n = 1). The median interval between haplo-HSCT and administration of the 1-day regimen was 26 days (range, 18 to 50 days). Fresh PBSC grafts were used in 9 patients, and cryopreserved PBSC grafts were used in 2 patients. Median cell viability was 99.6%, with a median stem cell dose of 7.2 × 10<sup>6</sup> CD34<sup>+</sup> cells/kg (range, 4.81 to 20.6 × 10<sup>6</sup> cells/kg) and a median total nucleated cell (TNC) dose of 8.0 × 10<sup>8<
背景:单倍体造血干细胞移植(haploo - hsct)越来越多地被用于缺乏合适的人类白细胞抗原匹配供体的患者的替代移植策略。t细胞耗损降低了移植物抗宿主病(GVHD)的风险,但代价是移植物衰竭的风险增加,如果冷冻保存的自体移植物无法抢救,则需要立即再次移植。传统的高强度修复与清髓和免疫消融方案持续约1周,旨在进一步抑制能够排斥原发移植物的受体来源免疫系统,其发病率和死亡率较高。缩短和降低强度的调理方案可能降低感染风险和死亡率,但持续植入将是一个降低强度的问题。目的:在这里,我们报告了11名儿童患者的良好结果,他们在各种恶性和非恶性疾病的初始清髓单倍造血干细胞移植后,因移植物衰竭而在再次移植前接受了1天降低强度的准备方案。研究设计:这是一项在香港儿童医院进行的回顾性研究,香港儿童医院是香港唯一的区域性儿童造血干细胞移植中心。所有在2021年6月1日至2024年5月31日期间因移植物失败而接受首次单倍造血干细胞移植并随后接受为期一天的非清髓性单倍造血干细胞移植的18岁或以下儿童患者均被纳入研究。挽救方案包括氟达拉滨(30mg/m2),环磷酰胺(2000mg/m2或60mg/kg)和阿仑单抗(0.3mg/kg),有或没有全身照射(2Gy),均在再次移植前1天给予。收集gcsf动员的外周血干细胞(PBSCs),并尽可能在没有体外t细胞耗尽的情况下进行新鲜移植,而如果无法进行新鲜分离,则使用冷冻保存的PBSCs。GVHD预防包括环孢素、霉酚酸酯、他克莫司或西罗莫司。结果:共纳入11例患者,其中男性9例,女性2例,中位年龄8.8岁(2.4-17.5岁)。潜在的疾病包括transfusion-dependent贫血(n = 7;beta-thalassemia主要 = 4,血红蛋白哈默史密斯 = 1,丙酮酸激酶缺乏症 = 1,严重的再生障碍性贫血 = 1),慢性肉芽肿性疾病(n = 1),急性淋巴细胞白血病(n = 1), post-liver移植淋巴增殖性疾病(n = 1)和神经母细胞瘤(n = 1)。单倍造血干细胞移植到使用一日方案的中位间隔为26天(范围18-50天)。9例患者使用新鲜PBSC移植,2例患者使用冷冻保存的PBSC移植。细胞存活率中位数为99.6%,干细胞中位数剂量为7.2 × 106个CD34+细胞/kg(范围4.81-20.6),总有核细胞剂量为8.0 × 108个/kg(范围5.17-10)。9例移植新鲜PBSC的患者均表现出持续的移植和造血功能恢复。中位中性粒细胞和血小板(≥20 × 109/L)分别在+12天(范围10-19)和+16天(范围10-35)植入。没有人发展为III/IV级急性GVHD或严重慢性GVHD。对于2例使用冷冻保存的PBSC移植物的患者,均导致移植物失败,其中1例通过使用新鲜PBSC移植物的另一个为期一天的方案成功挽救。另一名患者进行了自体再生,并在完全清髓后再次成功地接受了来自同一供体的单倍造血干细胞移植。在中位随访35个月(18-52个月)时,所有11例患者的总生存率均为100%。结论:本地经验表明,改良的1天低强度方案联合新鲜而非冷冻保存的PBSC移植物是可行的,有望实现持续植入。这是一种安全,适当的方法抢救儿科患者的移植失败,需要立即再移植。
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引用次数: 0
Applicability of Allogeneic Hematopoietic Cell Transplant for TP53-Mutated Myeloid Neoplasms: Are We There Yet? 同种异体造血细胞移植治疗tp53突变骨髓肿瘤的适用性:我们还在那里吗?
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2026.01.012
Mithun Vinod Shah
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引用次数: 0
Refined Elderly Comorbidity Index (RECI) Is Highly Predictive of Post-Transplant Survival in Older Adults with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) 精细化老年共病指数(RECI)可高度预测老年急性髓性白血病(AML)和骨髓增生异常综合征(MDS)患者移植后的生存
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2025.12.105
Fnu Amisha MD , Corbin Wright MD , Sean Haney MD , Pujan Patel MD , Biwei Cao PhD , Jongphil Kim PhD , Onyee Chan MD , Andrew T Kuykendall MD , Nancy Torres MD , Reshma Ramlal MD , Rawan Faramand MD , Abu-Sayeef Mirza MD, MPH , Fabiana Perna MD, PhD , Allison Walker MD , Asmita Mishra MD , Lia Elena Perez MD , Eric Padron MD , Aleksandr Lazaryan MD, MPH, PhD , Farhad Khimani MD , David A. Sallman MD , Nelli Bejanyan MD
<div><h3>Background</h3><div>Older age is a known risk factor for non-relapse mortality (NRM) after allogenic stem cell transplantation (HCT). Reduced-intensity conditioning (RIC) has made HCT- the only curative option- more accessible to elderly AML and MDS patients (pts). Age adjusted HCT comorbidity index (HCT-CI), though widely use, was developed from a heterogeneous cohort and its predictive accuracy may be limited by changes in clinical practice and patient characteristics over time. We present additional predictors of NRM and overall survival (OS) to introduce RECI for patients ≥60 years (yrs) receiving HCT for AML/MDS.</div></div><div><h3>Methods</h3><div>In this single-center retrospective study, we evaluated predictive markers and survival outcomes in 941 pts aged ≥60 yrs who underwent HCT (2005-2023) for AML or MDS (Fig 1). The primary endpoints were 2-year NRM and OS. Adjusted hazard ratios (HR) of significant variables from multivariate Cox model of NRM were converted to an integer score to develop the RECI. HR of 1.3-2, 2.1-3, and 3-4, were assigned weights of 1, 2, and 3, respectively. RECI, the sum of integer weights, was used to stratify patients according to 2-year NRM and OS.</div></div><div><h3>Results</h3><div>Baseline characteristics are summarized (Fig 1, 2). At 2-year post-HCT, NRM was 22% (95% CI: 20-25) and OS was 59% (95% CI: 56-62) for the entire cohort. In multivariate analysis, NRM and OS were similar in patients aged 60-69 and ≥70 years. NRM was higher with HCT-CI ≥3 (HR 1.61, 95% CI 1.19- 2.18, p=0.002), eGFR <60 (HR 1.83, 95% CI 1.26- 2.67, p=0.002), albumin <3.5 (HR 1.83, 95% CI 1.25- 2.65, p=0.002), and CMV R+ (HR 1.36, 95% CI 1.01- 1.83, p=0.04). OS was worse with HCT-CI ≥3 (HR 1.46, 95% CI 1.15- 1.86, p=0.0018), albumin <3.5 (HR 1.54, 95% CI 1.1- 2.16, p=0.01), ferritin ≥700 (HR 1.43, 95% CI 1.10- 1.87, p=0.007), and high risk AML/MDS (HR 1.58, 95% CI 1.25- 1.99, p= <0.0001).</div><div>Components of RECI are summarized (Fig 3). RECI ranged from 0 to 4 and stratified patients into 3 risk groups with score of 0 (33%), 1 (53%), and ≥2 (14%). RECI was strongly prognostic for 2-year NRM ranging from 15% (95% CI: 11-19) in RECI 0, 22% (95% CI: 19-26) in RECI 1 (HR=1.6, 95% CI 1.13-2.25, p=0.009) and 38% (95% CI: 29-46) in RECI ≥2 (HR=3.0, 95% CI 1.99-4.46, p<0.001) (Fig 4). The prognostic significance of RECI was also determined for OS ranging from 66% (95% CI: 61-72) in RICI 0, 58% (95% CI: 54-63) in RECI 1 (HR=1.3, 95% CI 1.04-1.68, p=0.02) and 44% (95% CI: 36-53) in RECI ≥2 (HR=2.2, 95% CI 1.60-2.91, p<0.0001) (Fig 4).</div></div><div><h3>Conclusions</h3><div>RECI applied at time of HCT strongly predicts NRM and OS in patients aged ≥60 with AML/MDS. No difference in survival outcomes was observed in patients aged 60-69 and ≥70 yrs. While elderly patients should be considered candidates for HCT, predictive factors that affect NRM and OS should be carefully assessed prior to HCT. If validated in l
背景:年龄是同种异体干细胞移植(HCT)术后非复发死亡率(NRM)的已知危险因素。低强度调节(RIC)使得HCT(唯一的治疗选择)更容易被老年AML和MDS患者接受。年龄调整的HCT共病指数(HCT- ci)虽然被广泛使用,但它是从异质队列中发展而来的,其预测准确性可能受到临床实践和患者特征随时间变化的限制。我们提出了NRM和总生存期(OS)的其他预测因素,以引入≥60岁(yrs)接受HCT治疗的AML/MDS患者的RECI。在这项单中心回顾性研究中,我们评估了941名年龄≥60岁的AML或MDS患者(2005-2023年)的预测标志物和生存结果(图1)。主要终点为2年NRM和OS。将NRM多变量Cox模型中显著变量的校正风险比(HR)转换为整数分值,形成RECI。HR分别为1.3-2、2.1-3和3-4,权重分别为1、2和3。采用整数权值和RECI,根据2年NRM和OS对患者进行分层。基线特征总结(图1、2)。在hct后2年,整个队列的NRM为22% (95% CI: 20-25), OS为59% (95% CI: 56-62)。在多变量分析中,60-69岁和≥70岁患者的NRM和OS相似。当HCT-CI≥3 (HR 1.61, 95% CI 1.19- 2.18, p=0.002)、eGFR <60 (HR 1.83, 95% CI 1.26- 2.67, p=0.002)、白蛋白<;3.5 (HR 1.83, 95% CI 1.25- 2.65, p=0.002)和CMV R+ (HR 1.36, 95% CI 1.01- 1.83, p=0.04)时,NRM较高。HCT-CI≥3 (HR 1.46, 95% CI 1.15- 1.86, p=0.0018)、白蛋白3.5 (HR 1.54, 95% CI 1.1- 2.16, p=0.01)、铁蛋白≥700 (HR 1.43, 95% CI 1.10- 1.87, p=0.007)和高风险AML/MDS (HR 1.58, 95% CI 1.25- 1.99, p= <0.0001)的OS较差。总结了RECI的组成部分(图3)。RECI评分范围从0到4,将患者分为3个危险组,分别为0分(33%)、1分(53%)和≥2分(14%)。RECI对2年NRM有很强的预后作用,RECI 0组为15% (95% CI: 11-19), RECI 1组为22% (95% CI: 19-26) (HR=1.6, 95% CI 1.13-2.25, p=0.009), RECI≥2组为38% (95% CI: 29-46) (HR=3.0, 95% CI 1.99-4.46, p<0.001)(图4)。RECI对OS的预后意义也被确定,范围从RICI 0的66% (95% CI: 61-72), RECI 1的58% (95% CI: 54-63) (HR=1.3, 95% CI 1.04-1.68, p=0.02)和RECI≥2的44% (95% CI: 36-53) (HR=2.2, 95% CI 1.60-2.91, p<0.0001)(图4)。结论在HCT时应用reci对≥60岁AML/MDS患者的NRM和OS有很强的预测作用。60-69岁和≥70岁患者的生存结局无差异。虽然老年患者应被视为HCT的候选者,但在HCT之前应仔细评估影响NRM和OS的预测因素。如果在大型独立HCT队列中得到验证,RECI作为一种新的预后工具可以帮助老年患者进行HCT的适当选择。
{"title":"Refined Elderly Comorbidity Index (RECI) Is Highly Predictive of Post-Transplant Survival in Older Adults with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)","authors":"Fnu Amisha MD ,&nbsp;Corbin Wright MD ,&nbsp;Sean Haney MD ,&nbsp;Pujan Patel MD ,&nbsp;Biwei Cao PhD ,&nbsp;Jongphil Kim PhD ,&nbsp;Onyee Chan MD ,&nbsp;Andrew T Kuykendall MD ,&nbsp;Nancy Torres MD ,&nbsp;Reshma Ramlal MD ,&nbsp;Rawan Faramand MD ,&nbsp;Abu-Sayeef Mirza MD, MPH ,&nbsp;Fabiana Perna MD, PhD ,&nbsp;Allison Walker MD ,&nbsp;Asmita Mishra MD ,&nbsp;Lia Elena Perez MD ,&nbsp;Eric Padron MD ,&nbsp;Aleksandr Lazaryan MD, MPH, PhD ,&nbsp;Farhad Khimani MD ,&nbsp;David A. Sallman MD ,&nbsp;Nelli Bejanyan MD","doi":"10.1016/j.jtct.2025.12.105","DOIUrl":"10.1016/j.jtct.2025.12.105","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Older age is a known risk factor for non-relapse mortality (NRM) after allogenic stem cell transplantation (HCT). Reduced-intensity conditioning (RIC) has made HCT- the only curative option- more accessible to elderly AML and MDS patients (pts). Age adjusted HCT comorbidity index (HCT-CI), though widely use, was developed from a heterogeneous cohort and its predictive accuracy may be limited by changes in clinical practice and patient characteristics over time. We present additional predictors of NRM and overall survival (OS) to introduce RECI for patients ≥60 years (yrs) receiving HCT for AML/MDS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this single-center retrospective study, we evaluated predictive markers and survival outcomes in 941 pts aged ≥60 yrs who underwent HCT (2005-2023) for AML or MDS (Fig 1). The primary endpoints were 2-year NRM and OS. Adjusted hazard ratios (HR) of significant variables from multivariate Cox model of NRM were converted to an integer score to develop the RECI. HR of 1.3-2, 2.1-3, and 3-4, were assigned weights of 1, 2, and 3, respectively. RECI, the sum of integer weights, was used to stratify patients according to 2-year NRM and OS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Baseline characteristics are summarized (Fig 1, 2). At 2-year post-HCT, NRM was 22% (95% CI: 20-25) and OS was 59% (95% CI: 56-62) for the entire cohort. In multivariate analysis, NRM and OS were similar in patients aged 60-69 and ≥70 years. NRM was higher with HCT-CI ≥3 (HR 1.61, 95% CI 1.19- 2.18, p=0.002), eGFR &lt;60 (HR 1.83, 95% CI 1.26- 2.67, p=0.002), albumin &lt;3.5 (HR 1.83, 95% CI 1.25- 2.65, p=0.002), and CMV R+ (HR 1.36, 95% CI 1.01- 1.83, p=0.04). OS was worse with HCT-CI ≥3 (HR 1.46, 95% CI 1.15- 1.86, p=0.0018), albumin &lt;3.5 (HR 1.54, 95% CI 1.1- 2.16, p=0.01), ferritin ≥700 (HR 1.43, 95% CI 1.10- 1.87, p=0.007), and high risk AML/MDS (HR 1.58, 95% CI 1.25- 1.99, p= &lt;0.0001).&lt;/div&gt;&lt;div&gt;Components of RECI are summarized (Fig 3). RECI ranged from 0 to 4 and stratified patients into 3 risk groups with score of 0 (33%), 1 (53%), and ≥2 (14%). RECI was strongly prognostic for 2-year NRM ranging from 15% (95% CI: 11-19) in RECI 0, 22% (95% CI: 19-26) in RECI 1 (HR=1.6, 95% CI 1.13-2.25, p=0.009) and 38% (95% CI: 29-46) in RECI ≥2 (HR=3.0, 95% CI 1.99-4.46, p&lt;0.001) (Fig 4). The prognostic significance of RECI was also determined for OS ranging from 66% (95% CI: 61-72) in RICI 0, 58% (95% CI: 54-63) in RECI 1 (HR=1.3, 95% CI 1.04-1.68, p=0.02) and 44% (95% CI: 36-53) in RECI ≥2 (HR=2.2, 95% CI 1.60-2.91, p&lt;0.0001) (Fig 4).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;RECI applied at time of HCT strongly predicts NRM and OS in patients aged ≥60 with AML/MDS. No difference in survival outcomes was observed in patients aged 60-69 and ≥70 yrs. While elderly patients should be considered candidates for HCT, predictive factors that affect NRM and OS should be carefully assessed prior to HCT. If validated in l","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Pages S70-S71"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098472","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}
引用次数: 0
A Cost-Conscious, and Highly Successful Start-up Strategy for Hematopoietic Cell Transplantation in Low- and Middle-Income Countries Supported By DKMS 在DKMS的支持下,低收入和中等收入国家具有成本意识和高度成功的造血细胞移植启动策略
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2025.12.043
Thomas E Klingebiel MD, Prof. , Mohana Reddy MD , Deepa Trivedi MD , Kim Hoa Nguyen Thi MD , Sayitov Begali MD , Hayder Shahad Marzook MD , Priya Marwah MD , Aliya Batool MD , Tejashree Sridhar MD , Rajat Kumar Agarwal MR , Jan Soerensen MD , Ali Suliman MD, MSc , Regina Landwehr Mrs , Lawrence Faulkner MD

Introduction

Sankalp India Foundation, in collaboration with DKMS and Cure2Children, developed a cost-conscious pediatric BMT model for low- and middle-income countries (LMICs). The strategy is supported by the DKMS Access to Treatment and Transplant program (ATT) and hinges on low-risk matched sibling donor (MSD) transplants for severe hemoglobinopathies delivered for an average cost of $12,000 including follow up.

Objectives

Here we summarize the outcomes of 141 MSD BMTs for hemoglobinopathies done directly in LMICs and compare experienced vs. startup centres assisted by the DKMS ATT program.

Methods

On-site and online expert guidance relying on a comprehensive online IT platform including electronical medical records and continuing quality improvement tools was implemented. Major emphasis was given to nurses’ training, and professional development. The protocol consisted of pre-transplant immunosuppression with fludarabine/dexamethasone followed one month later by fludarabine, busulfan and cyclophosphamide. G-CSF-primed bone marrow was used as stem cell source followed by cyclosporine/methotrexate prophylaxis. Moderate to severe Graft vs. Host Disease - and Event-Free Survival (GEFS) composite outcome was compared between established (BMJH-Bangalore, CIMS-Ahmedabad, SEAIT-Jaipur, India and ANTH-Islamabad, Pakistan) and startup centres (NCMC-Tashkent, Uzbekistan, HCH-Hue, Vietnam and Al Mujtaba Hospital-Kerbala, Iraq).

Results

A total of 141 consecutive first bone marrow transplants (BMTs) were included in the analysis, consisting 128 patients (median age: 6.04 years; IQR: 4.1–9.1 years) from established centres and 13 patients (median age: 5.12 years; IQR: 4.1–6.1 years) from startup centres.
Of the 128 patients treated at established centres, 122 were diagnosed with thalassemia major and 6 with sickle cell disease (SCD). All 13 patients at the startup centres had thalassemia major with liver size ≤3 cm below the costal margin at transplantation. GEFS was 94% in the established centres and 100% in the startup centres. Overall survival was 97% in established centres and 100% in startup centres, with a median follow-up of 12.8 months and 9.2 months in established respective start up centers. No statistically significant difference in GEFS was observed between the centres as determined by log-rank analysis.

Conclusions

The DKMS ATT platform focusing on low-risk MSD BMT for severe hemoglobinopathies seems to be a safe and effective BMT start up approach in LMICs maximizing initial success rates while promoting sustainability.
sankalp印度基金会与DKMS和Cure2Children合作,为中低收入国家(LMICs)开发了一种具有成本意识的儿科BMT模型。该战略得到DKMS获得治疗和移植计划(ATT)的支持,并依赖于为严重血红蛋白病提供低风险匹配的兄弟姐妹供体(MSD)移植,平均费用为12,000美元,包括随访。在这里,我们总结了141例在低收入国家直接进行的MSD BMTs治疗血红蛋白病的结果,并比较了经验丰富的中心和由DKMS ATT项目辅助的初创中心。方法依托包括电子病历和持续质量改进工具在内的综合在线IT平台,实施现场和在线专家指导。重点是护士的培训和专业发展。该方案包括移植前用氟达拉滨/地塞米松进行免疫抑制,1个月后用氟达拉滨、丁硫凡和环磷酰胺。用g - csf引物骨髓作为干细胞来源,然后用环孢素/甲氨蝶呤预防。在已建立中心(bmjh -班加罗尔、cims -艾哈迈达巴德、seait -斋浦尔,印度和anth -伊斯兰堡,巴基斯坦)和新成立中心(nmc -塔什干,乌兹别克斯坦、hch -顺化,越南和Al Mujtaba医院-克尔巴拉,伊拉克)之间比较了中重度移植物抗宿主病和无事件生存(GEFS)的综合结果。结果共纳入141例连续首次骨髓移植(BMTs),其中128例患者(中位年龄:6.04岁;IQR: 4.1-9.1岁)来自成熟中心,13例患者(中位年龄:5.12岁;IQR: 4.1-6.1岁)来自创业中心。在已建立的中心接受治疗的128名患者中,122人被诊断为重度地中海贫血,6人被诊断为镰状细胞病。启动中心的所有13例患者均为重度地中海贫血,移植时肝脏大小≤肋缘以下3cm。全球环境融资在已建立的中心占94%,在新成立的中心占100%。在已建立的中心,总体生存率为97%,在创业中心为100%,在已建立的创业中心,中位随访时间分别为12.8个月和9.2个月。经log-rank分析,中心间GEFS无统计学差异。结论DKMS ATT平台专注于重度血红蛋白病的低风险MSD BMT,似乎是中低收入国家一种安全有效的BMT启动方法,可最大限度地提高初始成功率,同时促进可持续性。
{"title":"A Cost-Conscious, and Highly Successful Start-up Strategy for Hematopoietic Cell Transplantation in Low- and Middle-Income Countries Supported By DKMS","authors":"Thomas E Klingebiel MD, Prof. ,&nbsp;Mohana Reddy MD ,&nbsp;Deepa Trivedi MD ,&nbsp;Kim Hoa Nguyen Thi MD ,&nbsp;Sayitov Begali MD ,&nbsp;Hayder Shahad Marzook MD ,&nbsp;Priya Marwah MD ,&nbsp;Aliya Batool MD ,&nbsp;Tejashree Sridhar MD ,&nbsp;Rajat Kumar Agarwal MR ,&nbsp;Jan Soerensen MD ,&nbsp;Ali Suliman MD, MSc ,&nbsp;Regina Landwehr Mrs ,&nbsp;Lawrence Faulkner MD","doi":"10.1016/j.jtct.2025.12.043","DOIUrl":"10.1016/j.jtct.2025.12.043","url":null,"abstract":"<div><h3>Introduction</h3><div>Sankalp India Foundation, in collaboration with DKMS and Cure2Children, developed a cost-conscious pediatric BMT model for low- and middle-income countries (LMICs). The strategy is supported by the DKMS Access to Treatment and Transplant program (ATT) and hinges on low-risk matched sibling donor (MSD) transplants for severe hemoglobinopathies delivered for an average cost of $12,000 including follow up.</div></div><div><h3>Objectives</h3><div>Here we summarize the outcomes of 141 MSD BMTs for hemoglobinopathies done directly in LMICs and compare experienced <em>vs.</em> startup centres assisted by the DKMS ATT program.</div></div><div><h3>Methods</h3><div>On-site and online expert guidance relying on a comprehensive online IT platform including electronical medical records and continuing quality improvement tools was implemented. Major emphasis was given to nurses’ training, and professional development. The protocol consisted of pre-transplant immunosuppression with fludarabine/dexamethasone followed one month later by fludarabine, busulfan and cyclophosphamide. G-CSF-primed bone marrow was used as stem cell source followed by cyclosporine/methotrexate prophylaxis. Moderate to severe Graft vs. Host Disease - and Event-Free Survival (GEFS) composite outcome was compared between established (BMJH-Bangalore, CIMS-Ahmedabad, SEAIT-Jaipur, India and ANTH-Islamabad, Pakistan) and startup centres (NCMC-Tashkent, Uzbekistan, HCH-Hue, Vietnam and Al Mujtaba Hospital-Kerbala, Iraq).</div></div><div><h3>Results</h3><div>A total of 141 consecutive first bone marrow transplants (BMTs) were included in the analysis, consisting 128 patients (median age: 6.04 years; IQR: 4.1–9.1 years) from established centres and 13 patients (median age: 5.12 years; IQR: 4.1–6.1 years) from startup centres.</div><div>Of the 128 patients treated at established centres, 122 were diagnosed with thalassemia major and 6 with sickle cell disease (SCD). All 13 patients at the startup centres had thalassemia major with liver size ≤3 cm below the costal margin at transplantation. GEFS was 94% in the established centres and 100% in the startup centres. Overall survival was 97% in established centres and 100% in startup centres, with a median follow-up of 12.8 months and 9.2 months in established respective start up centers. No statistically significant difference in GEFS was observed between the centres as determined by log-rank analysis.</div></div><div><h3>Conclusions</h3><div>The DKMS ATT platform focusing on low-risk MSD BMT for severe hemoglobinopathies seems to be a safe and effective BMT start up approach in LMICs maximizing initial success rates while promoting sustainability.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S25"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098507","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}
引用次数: 0
Acrobat Interim Results: Peripheral Blood-Based Alloheme Test Enables Robust Relapse Surveillance in Post-HCT AML and MDS Patients Acrobat中期结果:基于外周血的异素血红素检测能够对hct后AML和MDS患者进行稳健的复发监测
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2025.12.082
Ran Reshef MD, MSc , Stefan O Ciurea MD , Ronald M. Sobecks MD , Dr. Iskra Pusic MD, MScI , Nelli Bejanyan MD , Sagar S. Patel MD , Arpita P. Gandhi MD , Vamsi Kota MD , M. Nabeel Rajeh MD , Piyanuch Kongtim MD, PhD , Jing Shi PhD , Yi Fu PhD , Natali Gulbahce PhD , Nishant Dwivedi MD, PhD , Monzr M. Al Malki MD , Corey Cutler MD MPH
<div><h3>Introduction</h3><div>Early detection of relapses in patients undergoing allogeneic hematopoietic cell transplantation (HCT) may enable early intervention. The ACROBAT study (NCT04635384) evaluates the use of AlloHeme, a next-generation sequencing (NGS)-based, ultra-sensitive monitoring test for relapse prediction in post-HCT patients.</div></div><div><h3>Methods</h3><div>Post-HCT acute myeloid leukemia (AML) and or myelodysplastic syndrome (MDS) patients enrolled in ACROBAT were included in this analysis. Testing was performed at 14 post-HCT time points over 2 years, as outlined in the study protocol. An increase of ≥0.2% in recipient chimerism between two consecutive time points was defined as increasing mixed chimerism (iMC) and an AlloHeme test positive. Treating physicians determined relapses per the Center for International Blood & Marrow Transplant Research criteria. Here we describe the findings of the 18-month interim analysis with the intent of presenting the final study readout for all subjects at Tandem Meetings 2026.</div></div><div><h3>Results</h3><div>Table 1 presents the demographics and disease characteristics of 227 enrolled AML and MDS patients. Out of the 227 enrolled patients, 32 subjects were excluded from the analysis due to events (non-relapse mortality (NRM), study withdrawal, and relapses) that occurred before the two tests used to determine iMC. Among the remaining 195 subjects with 18+ months of follow-up (median, 23.4 months; range, 1.8-24), 37 subjects (19%) experienced relapse, and 26 (13.3%) subjects had non-relapse mortality (NRM). AlloHeme had an AUC of 86% for relapse prediction based on sensitivity (88%), specificity (85%), PPV (60%), and NPV (97%). In comparison, modeling at the STR-PCR threshold of 1% iMC and site-reported multi-flow cytometry measurable residual disease (MFC-MRD) demonstrated lower sensitivity to predict relapse (Table 2). A time-varying risk model showed that the relapse risk for patients with an iMC is 54.0 times (95% CI = 22.4, 142.8; p < 0.001) higher than that of non-iMC patients. 3- and 6-month landmark analyses demonstrated significantly higher relapse incidence in subjects with iMC compared with non-iMC (p-values < 0.05) (Figure 1). Among subjects who were iMC positive before or at the time of the relapse event, the test provided a median lead time of 36 days to clinical relapse (IQR: 18–72 days), with 47% of relapses identified at least 45 days before the relapse.</div><div>Further optimizing the performance for risk prediction by incorporating additional AlloHeme cell subtype analytes into an algorithm improved specificity to >92% and PPV to >74% without affecting sensitivity and NPV.</div></div><div><h3>Conclusion</h3><div>ACROBAT interim results demonstrate that AlloHeme monitoring for post-HCT AML and MDS patients can identify relapses with a significant lead time compared to traditional methods of relapse detection, which could enable timely interventio
在接受同种异体造血细胞移植(HCT)的患者中,早期发现复发可能有助于早期干预。ACROBAT研究(NCT04635384)评估了AlloHeme的使用,这是一种基于下一代测序(NGS)的超敏感监测试验,用于预测hct后患者的复发。方法纳入ACROBAT的hct后急性髓性白血病(AML)和/或骨髓增生异常综合征(MDS)患者。如研究方案所述,在hct后2年内的14个时间点进行了测试。连续两个时间点之间受体嵌合增加≥0.2%定义为混合嵌合(iMC)增加和AlloHeme检测阳性。治疗医生根据国际血液和骨髓移植研究中心的标准确定复发。在这里,我们描述了为期18个月的中期分析的结果,目的是在2026年串联会议上公布所有受试者的最终研究结果。结果stable 1显示了227例入组AML和MDS患者的人口统计学特征和疾病特征。在227名入组患者中,32名受试者由于在用于确定iMC的两项测试之前发生的事件(非复发死亡率(NRM)、研究退出和复发)而被排除在分析之外。其余195例随访18个月以上(中位23.4个月,范围1.8-24个月),37例(19%)复发,26例(13.3%)无复发死亡率(NRM)。基于敏感性(88%)、特异性(85%)、PPV(60%)和NPV (97%), AlloHeme预测复发的AUC为86%。相比之下,在1% iMC的STR-PCR阈值和多点报告的多流式细胞术可测量残留病(MFC-MRD)下建模,预测复发的敏感性较低(表2)。时变风险模型显示,iMC患者的复发风险是非iMC患者的54.0倍(95% CI = 22.4,142.8;p < 0.001)。3个月和6个月的里程碑分析显示,iMC患者的复发率明显高于非iMC患者(p值<; 0.05)(图1)。在复发事件前或复发时iMC阳性的受试者中,该测试提供了临床复发的中位提前时间为36天(IQR: 18-72天),47%的复发在复发前至少45天被发现。通过将额外的AlloHeme细胞亚型分析物纳入算法,进一步优化了风险预测的性能,在不影响灵敏度和NPV的情况下,将特异性提高到92%,PPV提高到74%。结论acrobat中期结果表明,与传统的复发检测方法相比,对hct后AML和MDS患者进行AlloHeme监测可以提前明显地识别复发,从而能够及时干预。
{"title":"Acrobat Interim Results: Peripheral Blood-Based Alloheme Test Enables Robust Relapse Surveillance in Post-HCT AML and MDS Patients","authors":"Ran Reshef MD, MSc ,&nbsp;Stefan O Ciurea MD ,&nbsp;Ronald M. Sobecks MD ,&nbsp;Dr. Iskra Pusic MD, MScI ,&nbsp;Nelli Bejanyan MD ,&nbsp;Sagar S. Patel MD ,&nbsp;Arpita P. Gandhi MD ,&nbsp;Vamsi Kota MD ,&nbsp;M. Nabeel Rajeh MD ,&nbsp;Piyanuch Kongtim MD, PhD ,&nbsp;Jing Shi PhD ,&nbsp;Yi Fu PhD ,&nbsp;Natali Gulbahce PhD ,&nbsp;Nishant Dwivedi MD, PhD ,&nbsp;Monzr M. Al Malki MD ,&nbsp;Corey Cutler MD MPH","doi":"10.1016/j.jtct.2025.12.082","DOIUrl":"10.1016/j.jtct.2025.12.082","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Early detection of relapses in patients undergoing allogeneic hematopoietic cell transplantation (HCT) may enable early intervention. The ACROBAT study (NCT04635384) evaluates the use of AlloHeme, a next-generation sequencing (NGS)-based, ultra-sensitive monitoring test for relapse prediction in post-HCT patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Post-HCT acute myeloid leukemia (AML) and or myelodysplastic syndrome (MDS) patients enrolled in ACROBAT were included in this analysis. Testing was performed at 14 post-HCT time points over 2 years, as outlined in the study protocol. An increase of ≥0.2% in recipient chimerism between two consecutive time points was defined as increasing mixed chimerism (iMC) and an AlloHeme test positive. Treating physicians determined relapses per the Center for International Blood &amp; Marrow Transplant Research criteria. Here we describe the findings of the 18-month interim analysis with the intent of presenting the final study readout for all subjects at Tandem Meetings 2026.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Table 1 presents the demographics and disease characteristics of 227 enrolled AML and MDS patients. Out of the 227 enrolled patients, 32 subjects were excluded from the analysis due to events (non-relapse mortality (NRM), study withdrawal, and relapses) that occurred before the two tests used to determine iMC. Among the remaining 195 subjects with 18+ months of follow-up (median, 23.4 months; range, 1.8-24), 37 subjects (19%) experienced relapse, and 26 (13.3%) subjects had non-relapse mortality (NRM). AlloHeme had an AUC of 86% for relapse prediction based on sensitivity (88%), specificity (85%), PPV (60%), and NPV (97%). In comparison, modeling at the STR-PCR threshold of 1% iMC and site-reported multi-flow cytometry measurable residual disease (MFC-MRD) demonstrated lower sensitivity to predict relapse (Table 2). A time-varying risk model showed that the relapse risk for patients with an iMC is 54.0 times (95% CI = 22.4, 142.8; p &lt; 0.001) higher than that of non-iMC patients. 3- and 6-month landmark analyses demonstrated significantly higher relapse incidence in subjects with iMC compared with non-iMC (p-values &lt; 0.05) (Figure 1). Among subjects who were iMC positive before or at the time of the relapse event, the test provided a median lead time of 36 days to clinical relapse (IQR: 18–72 days), with 47% of relapses identified at least 45 days before the relapse.&lt;/div&gt;&lt;div&gt;Further optimizing the performance for risk prediction by incorporating additional AlloHeme cell subtype analytes into an algorithm improved specificity to &gt;92% and PPV to &gt;74% without affecting sensitivity and NPV.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;ACROBAT interim results demonstrate that AlloHeme monitoring for post-HCT AML and MDS patients can identify relapses with a significant lead time compared to traditional methods of relapse detection, which could enable timely interventio","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S53"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098519","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}
引用次数: 0
Mature Outcomes from the Phase I Trial of Orca-T and Allogeneic CD19/CD22 CAR-T cells for Adults with High-Risk B-ALL Orca-T和同种异体CD19/CD22 CAR-T细胞治疗成人高风险B-ALL的I期试验的成熟结果
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2025.12.047
Alfonso Molina MD, MPH , Parveen Shiraz MD , Alyssa Kanegai MPH , Ayesha Fraser CCRP, CHRC , Diana Kordek RN , Caroline Wagner BS , Lindsay Danley BS , Arvind Ramakrishnan BS , Hossein Daghagh MS , Yingwen Huang MS , Gaurav Dhapola MS , Aman Siddiqui BS, MBA , Sally Arai MD, MS , Sushma Bharadwaj MD , Saurabh Dahiya MD, FACP , Hany Elmariah MD , Matthew Frank MD, PhD , Hitomi Hosoya MD, PhD , Vanessa E Kennedy MD , Laura Johnston MD , Lori S. Muffly MD, MS
<div><h3>Background</h3><div>High-risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) remains difficult to cure in adults despite autologous CAR T cells or allogeneic hematopoietic cell transplant (HCT). Building on preclinical work showing CAR T cell safety post-HCT (Ghosh A, Smith M <em>Nature Medicine</em> 2017), we tested whether allogeneic CAR-T cells combined with myeloablative graft-engineered HCT (Orca-T) could enhance antileukemic activity without increasing GVHD or graft failure. We now report final clinical outcomes from this Phase 1 trial (NCT05507827).</div></div><div><h3>Methods</h3><div>This single-center trial tested allogeneic anti-CD19/CD22 CAR T cells combined with myeloablative conditioning and Orca-T (D0 HSPCs/Tregs; D+2 Tcons, per Meyer <em>Blood</em> 2025) in adults with HR B-ALL. Donor-derived CAR T cells were administered on D+2, tacrolimus began on D+3. The primary endpoint was engraftment without grade 3+ acute GVHD at D+42; secondary endpoints included survival outcomes, CAR persistence, and immune reconstitution.</div></div><div><h3>Results</h3><div>Eighteen patients (pts) enrolled between Sept 2022 and May 2025; 16 received both Orca-T and allogeneic CAR T cells; 1 received only Orca-T due to active infection at time of planned CAR T infusion and 1 did not proceed on trial. Median age was 31 years (range, 21–58); 70% were Hispanic, 76% were MRD+ post-induction. Most (76%) received matched sibling grafts; 24% were from matched unrelated donors. All pts have now reached the primary endpoint: engraftment occurred in 100% and no pts have developed 3+ acute GVHD. Acute GVHD occurred in 1 pt (grade 1) and chronic GVHD in 2 pts (1 mild; 1 moderate). There were no high-grade CAR mediated toxicities.</div><div>With median follow-up of 14 months (range, 3-35), disease-free and overall survival are both 100% (Figure 1A, 1B). Figure 1C depicts pre-and post-treatment MRD. Following allogeneic CAR T plus Orca-T, all pts achieved MRD clearance by flow cytometry (10-4) and remain undetectable to date. Two pts with pre-treatment MRD have ongoing detectable MRD by clonoSEQ (10-6) without evidence of relapse. Median time to peak CAR expansion was 13 days. Median circulating CAR T cells at peak expansion was 1,205 copies/100ng DNA, with a median D0-28 AUC of 13,324 copies/100ng DNA. <strong>Figure 2</strong> shows ongoing CAR detection by qPCR (LOD 10 copies/100ng DNA) averaged across patients; only 4 pts have evidence of functional B cell recovery.</div></div><div><h3>Conclusion</h3><div>Here, we report final safety and anti-tumor activity of the combination of allogeneic anti-CD19/CD22 CAR T cells with a myeloablative graft-engineered HCT in pts with HR B-ALL. This paradigm-shifting combination of CAR T and HCT resulted in 100% DFS without graft failure, significant GVHD, or severe CAR-mediated toxicity. We hypothesize this is due to tolerance for CAR molecules, resulting in persistent CAR expression and improved antitumor activity.
成人高危(HR) b细胞急性淋巴细胞白血病(B-ALL)仍然难以治愈,尽管采用自体CAR - T细胞或同种异体造血细胞移植(HCT)。在临床前研究显示HCT后CAR-T细胞安全性的基础上(Ghosh A, Smith M Nature Medicine 2017),我们测试了异体CAR-T细胞联合骨髓清除移植工程HCT (Orca-T)是否可以增强抗白血病活性,而不会增加GVHD或移植物失败。我们现在报告该1期试验(NCT05507827)的最终临床结果。方法:这项单中心试验检测了同种异体抗cd19 /CD22 CAR -T细胞联合清髓调节和Orca-T (D0 HSPCs/Tregs; D+2 Tcons, per Meyer Blood 2025)在成人HR B-ALL患者中的应用。供体来源的CAR - T细胞在D+2给予,他克莫司在D+3开始。主要终点是在D+42时无3级急性GVHD的移植;次要终点包括生存结局、CAR持续性和免疫重建。结果2022年9月至2025年5月入组患者18例;16例同时接受Orca-T和同种异体CAR -T细胞;1例患者在计划CAR -T输注时因活动性感染仅接受了Orca-T, 1例患者未进行试验。中位年龄31岁(范围21-58岁);70%为西班牙裔,76%为入职后MRD+。大多数(76%)接受了匹配的同胞移植物;24%来自匹配的非亲属捐赠者。所有患者现在都达到了主要终点:移植的发生率为100%,没有患者发展为3+急性GVHD。1例患者发生急性GVHD(1级),2例患者发生慢性GVHD(1例轻度,1例中度)。没有CAR介导的高级别毒性。中位随访14个月(范围3-35),无病生存率和总生存率均为100%(图1A, 1B)。图1C描述了处理前和处理后的MRD。同种异体CAR -T + Orca-T治疗后,所有患者通过流式细胞术(10-4)达到MRD清除,并且迄今为止仍无法检测到。两名治疗前MRD患者通过克隆seq检测到MRD(10-6),但没有复发的证据。中非共和国扩张达到峰值的中位时间为13天。扩增峰值时循环CAR - T细胞的中位数为1205拷贝/100ng DNA,中位数D0-28 AUC为13324拷贝/100ng DNA。图2显示了正在进行的CAR检测的qPCR (LOD 10拷贝/100ng DNA)在患者中的平均水平;只有4例患者有B细胞功能恢复的证据。结论:我们报告了同种异体抗cd19 /CD22 CAR - T细胞与清骨髓移植工程HCT联合治疗HR B-ALL患者的最终安全性和抗肿瘤活性。这种范式转换的CAR- T和HCT的结合导致了100%的DFS,没有移植物衰竭、明显的GVHD或严重的CAR介导的毒性。我们假设这是由于对CAR分子的耐受性,导致CAR的持续表达和抗肿瘤活性的提高。我们的all-in- all- car - hct代表了一种合理的方法,值得进一步的研究。
{"title":"Mature Outcomes from the Phase I Trial of Orca-T and Allogeneic CD19/CD22 CAR-T cells for Adults with High-Risk B-ALL","authors":"Alfonso Molina MD, MPH ,&nbsp;Parveen Shiraz MD ,&nbsp;Alyssa Kanegai MPH ,&nbsp;Ayesha Fraser CCRP, CHRC ,&nbsp;Diana Kordek RN ,&nbsp;Caroline Wagner BS ,&nbsp;Lindsay Danley BS ,&nbsp;Arvind Ramakrishnan BS ,&nbsp;Hossein Daghagh MS ,&nbsp;Yingwen Huang MS ,&nbsp;Gaurav Dhapola MS ,&nbsp;Aman Siddiqui BS, MBA ,&nbsp;Sally Arai MD, MS ,&nbsp;Sushma Bharadwaj MD ,&nbsp;Saurabh Dahiya MD, FACP ,&nbsp;Hany Elmariah MD ,&nbsp;Matthew Frank MD, PhD ,&nbsp;Hitomi Hosoya MD, PhD ,&nbsp;Vanessa E Kennedy MD ,&nbsp;Laura Johnston MD ,&nbsp;Lori S. Muffly MD, MS","doi":"10.1016/j.jtct.2025.12.047","DOIUrl":"10.1016/j.jtct.2025.12.047","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;High-risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) remains difficult to cure in adults despite autologous CAR T cells or allogeneic hematopoietic cell transplant (HCT). Building on preclinical work showing CAR T cell safety post-HCT (Ghosh A, Smith M &lt;em&gt;Nature Medicine&lt;/em&gt; 2017), we tested whether allogeneic CAR-T cells combined with myeloablative graft-engineered HCT (Orca-T) could enhance antileukemic activity without increasing GVHD or graft failure. We now report final clinical outcomes from this Phase 1 trial (NCT05507827).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This single-center trial tested allogeneic anti-CD19/CD22 CAR T cells combined with myeloablative conditioning and Orca-T (D0 HSPCs/Tregs; D+2 Tcons, per Meyer &lt;em&gt;Blood&lt;/em&gt; 2025) in adults with HR B-ALL. Donor-derived CAR T cells were administered on D+2, tacrolimus began on D+3. The primary endpoint was engraftment without grade 3+ acute GVHD at D+42; secondary endpoints included survival outcomes, CAR persistence, and immune reconstitution.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Eighteen patients (pts) enrolled between Sept 2022 and May 2025; 16 received both Orca-T and allogeneic CAR T cells; 1 received only Orca-T due to active infection at time of planned CAR T infusion and 1 did not proceed on trial. Median age was 31 years (range, 21–58); 70% were Hispanic, 76% were MRD+ post-induction. Most (76%) received matched sibling grafts; 24% were from matched unrelated donors. All pts have now reached the primary endpoint: engraftment occurred in 100% and no pts have developed 3+ acute GVHD. Acute GVHD occurred in 1 pt (grade 1) and chronic GVHD in 2 pts (1 mild; 1 moderate). There were no high-grade CAR mediated toxicities.&lt;/div&gt;&lt;div&gt;With median follow-up of 14 months (range, 3-35), disease-free and overall survival are both 100% (Figure 1A, 1B). Figure 1C depicts pre-and post-treatment MRD. Following allogeneic CAR T plus Orca-T, all pts achieved MRD clearance by flow cytometry (10-4) and remain undetectable to date. Two pts with pre-treatment MRD have ongoing detectable MRD by clonoSEQ (10-6) without evidence of relapse. Median time to peak CAR expansion was 13 days. Median circulating CAR T cells at peak expansion was 1,205 copies/100ng DNA, with a median D0-28 AUC of 13,324 copies/100ng DNA. &lt;strong&gt;Figure 2&lt;/strong&gt; shows ongoing CAR detection by qPCR (LOD 10 copies/100ng DNA) averaged across patients; only 4 pts have evidence of functional B cell recovery.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Here, we report final safety and anti-tumor activity of the combination of allogeneic anti-CD19/CD22 CAR T cells with a myeloablative graft-engineered HCT in pts with HR B-ALL. This paradigm-shifting combination of CAR T and HCT resulted in 100% DFS without graft failure, significant GVHD, or severe CAR-mediated toxicity. We hypothesize this is due to tolerance for CAR molecules, resulting in persistent CAR expression and improved antitumor activity.","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"32 2","pages":"Page S27"},"PeriodicalIF":4.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098560","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}
引用次数: 0
Safety and Efficacy of AZD0120, a BCMA/CD19 Dual-Targeting CAR T-cell Therapy, in relapsed/refractory Multiple Myeloma: Preliminary Results from the DURGA-1 phase 1b/2 Study BCMA/CD19双靶向CAR - t细胞疗法AZD0120治疗复发/难治性多发性骨髓瘤的安全性和有效性:DURGA-1 1b/2期研究的初步结果
IF 4.4 3区 医学 Q2 HEMATOLOGY Pub Date : 2026-02-01 DOI: 10.1016/j.jtct.2025.12.054
Shambavi Richard MD , Mahmoud Gaballa MMBCh , Tara Gregory MD , Saurabh Chhabra MD, MS , Larry D. Anderson Jr. MD, PhD , Luciano J. Costa MD, PhD , Caitlin Costello MD , Scott R. Goldsmith MD , Doris K. Hansen MD , Sridevi Rajeeve MD , Shaji Kumar MD , Dr. Aravind Ramakrishnan MD , Minoo Battiwalla MD, MS , Ajay K. Nooka MD, MPH , Hira Shaikh MBBS , Meiyue G. Hong MD , Steven Wang MS , Patricia Cheung PhD , Liang Li PhD , Binod Dhakal MD
<div><h3>Introduction</h3><div>Multiple myeloma (MM) accounts for nearly 20% of all hematologic cancers in the US and remains a substantial clinical burden. While BCMA-directed CAR T-cell therapy has improved outcomes, challenges persist. AZD0120 (formerly GC012F) is a first-in-class autologous BCMA/CD19 dual-targeting CAR T-cell therapy using the FasTCAR rapid manufacturing platform. We report preliminary phase 1b results from DURGA-1, an ongoing phase 1b/2 trial evaluating AZD0120 in patients (pts) with relapsed/refractory (RR) MM.</div></div><div><h3>Methods</h3><div>This open-label, single-arm, US-based, multicenter study (NCT05850234) evaluated the safety of 2 dose levels (DLs) of AZD0120. Eligible pts were ≥18 y with RRMM (3+ prior lines of therapy [pLOT]), ECOG PS 0–1, and evidence of progressive disease. Prior BCMA-directed therapy ≥6 mo with best response of partial response or better was permitted. Pts received a single infusion of AZD0120 (DL1: 1×10<sup>5</sup> cells/kg; DL2: 3×10<sup>5</sup> cells/kg). Phase 1b primary objectives: safety/tolerability, RP2D determination; secondary objectives: efficacy, cellular kinetics (CK), pharmacodynamics.</div></div><div><h3>Results</h3><div>At data cutoff (DCO; 18 July 2025), 25 pts received AZD0120 (n=12 DL1; n=13 DL2). Median age was 64 y (range 44–78), median pLOT was 4 (range 3–7), 72% were triple-class refractory, 20% had prior BCMA CAR T-cell therapy, and 28% had high-risk cytogenetic features. Median time from apheresis to infusion was 28 d (range 19–44); 5 pts received bridging therapy. Median follow-up was 1.4 mo (range 0–19.3). No dose-limiting toxicities were reported. Most common treatment-emergent AEs (any grade) were CRS (64%), neutrophil count decreased (56%), and anemia (32%). CRS was reported in 75% (DL1) and 54% (DL2) of pts, with no cases grade ≥3. Median time to CRS onset (DL1/DL2) was 9 d (range 2–11); 12 pts (48%) received tocilizumab to manage CRS. No deaths or cases of ICANSEC-colitis, or secondary primary malignancies were reported. For efficacy-evaluable pts (n=15), overall response rate was 100% and complete response rate was 33%; median time to response was 0.9 mo for both DLs (range 0.6–1.9). All pts evaluable for minimal residual disease (MRD; n=5 DL1; n=3 DL2; DCO 1 July 2025) were MRD negative by next-generation sequencing (10<sup>-5</sup> sensitivity). Three pts in DL1 with ≥12 mo follow-up maintained MRD negativity. CK analysis from 16 evaluable pts (DCO 12 June 2025) demonstrated median T<sub>max</sub> of 13 d post-infusion and median persistence of 42 d (range 13–273). Updated clinical data will be presented.</div></div><div><h3>Conclusion</h3><div>Preliminary phase 1b results demonstrated AZD0120 was well tolerated, with a low incidence of serious AEs, no grade ≥3 CRS, and no ICANS. FasTCAR-manufactured AZD0120 had controlled in vivo expansion leading to a predictable safety profile. A single infusion of AZD0120 achieved early, deep responses with 100% MRD ne
在美国,多发性骨髓瘤(MM)占所有血液学癌症的近20%,仍然是一个巨大的临床负担。虽然bcma导向的CAR - t细胞疗法改善了结果,但挑战依然存在。AZD0120(前身为GC012F)是一种使用FasTCAR快速制造平台的一流自体BCMA/CD19双靶向CAR -t细胞疗法。dulga -1是一项正在进行的1b/2期临床试验,评估AZD0120在复发/难治性(RR) mm患者(pts)中的疗效。方法:这项开放标签、单臂、美国多中心研究(NCT05850234)评估了2个剂量水平(dl) AZD0120的安全性。符合条件的患者为≥18岁,RRMM(3+既往治疗线[pLOT]), ECOG PS 0-1,且有疾病进展的证据。允许既往bcma定向治疗≥6个月,最佳反应或部分反应更好。患者接受单次输注AZD0120 (DL1: 1×105 cells/kg; DL2: 3×105 cells/kg)。1b期主要目标:安全性/耐受性,RP2D测定;次要目标:功效,细胞动力学(CK),药效学。结果sat数据截止日期(DCO; 2025年7月18日),25例患者接受AZD0120治疗(n=12 DL1; n=13 DL2)。中位年龄为64岁(范围44-78),中位pLOT为4(范围3-7),72%为三级难治性,20%既往接受过BCMA CAR - t细胞治疗,28%具有高危细胞遗传学特征。从采血到输注的中位时间为28 d(范围19-44);5例患者接受桥接治疗。中位随访时间为1.4个月(范围0-19.3)。没有剂量限制性毒性的报告。最常见的治疗突发不良事件(任何级别)是CRS(64%),中性粒细胞计数减少(56%)和贫血(32%)。75% (DL1)和54% (DL2)的患者报告了CRS,没有分级≥3的病例。发生CRS的中位时间(DL1/DL2)为9天(范围2-11);12名患者(48%)接受tocilizumab治疗CRS。无icansc结肠炎或继发性原发性恶性肿瘤死亡或病例报告。对于可评估疗效的患者(n=15),总缓解率为100%,完全缓解率为33%;两种dl的中位反应时间为0.9个月(范围0.6-1.9)。所有可评估最小残留疾病的患者(MRD; n=5 DL1; n=3 DL2; DCO于2025年7月1日)通过下一代测序(10-5灵敏度)均为MRD阴性。3例DL1患者随访≥12个月后维持MRD阴性。来自16个可评估患者(DCO为2025年6月12日)的CK分析显示,注射后的中位Tmax为13天,中位持续时间为42天(范围13 - 273)。将介绍最新的临床数据。初步1b期结果显示AZD0120耐受性良好,严重ae发生率低,无≥3级CRS,无ICANS。fastcar生产的AZD0120具有可控制的体内扩张,因此具有可预测的安全性。AZD0120单次输注在三级暴露的RRMM患者中获得了早期、深度的100% MRD阴性反应。
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Transplantation and Cellular Therapy
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