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Superior Survival After Unrelated Allogeneic Stem Cell Transplantation With Low-Dose ATG Compared to Low-Dose TBI in Myeloablative Fludarabine/Busulfan-Based Regimen for MDS on Behalf of the Adult MDS Working Group of the JSTCT 在基于氟达拉滨/布磺凡的髓鞘消融治疗MDS方案中,与低剂量TBI相比,使用低剂量ATG进行非亲属异基因干细胞移植后的存活率更高。
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.jtct.2024.09.026
Machiko Fujioka , Hidehiro Itonaga , Hideyuki Nakazawa , Tetsuya Nishida , Keisuke Kataoka , Takashi Ikeda , Shinichi Kako , Ken-ichi Matsuoka , Koji Adachi , Shin-ichiro Fujiwara , Nobuyuki Aotsuka , Toshiro Kawakita , Emiko Sakaida , Yoshinobu Kanda , Tatsuo Ichinohe , Yoshiko Atsuta , Yasushi Miyazaki , Ken Ishiyama
The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-years overall survival (OS) rates were 39.9%, 64.8%, and 43.7%; 3-years nonrelapse mortality (NRM) were 32.1%, 22.1%, and 27.1%; and 3-years relapse incidences were 34.7%, 21.2%, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27 to 0.95; P = .032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36; 95% CI, 0.13 to 1.06; P = .063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27 to 0.99, P = .049) and NRM (HR 0.034, 95% CI 0.11 to 0.92, P = .034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors.
在骨髓增生异常综合征(MDS)的异基因造血干细胞移植中,氟达拉滨/静脉注射12.8 mg/kg(FB4)方案是一种有效的调理方案;然而,关于FB4与低剂量抗胸腺球蛋白(ATG ≤ 5 mg/kg)或低剂量全身照射(TBI ≤ 4 Gy)对预后影响的数据却很有限。因此,我们回顾性评估了2009年至2018年期间首次接受非亲属供体移植的280例成人新发MDS患者的治疗效果。中位年龄为61岁(16至70岁)。在单用FB4组(FB4)、FB4加ATG组(FB4-ATG)和FB4加TBI组(FB4-TBI)中,3年总生存率(OS)分别为39.9%、64.8%和43.7%;3年非复发死亡率(NRM)分别为32.1%、22.1%和27.1%;3年复发率分别为34.7%、21.2%和28.9%。多变量分析显示,与FB4组相比,FB4-ATG组与更好的OS显著相关(危险比[HR],0.51;95%置信区间[CI],0.27-0.95;P=0.032)。与 FB4 组相比,FB4-ATG 组往往与较低的 NRM 相关(HR,0.36;95% CI,0.13-1.06;P=0.063)。与 FB4-TBI 组相比,FB4-ATG 组显示出更好的 OS(HR 0.52,95% CI 0.27-0.99,P=0.049)和 NRM(HR 0.034,95% CI 0.11-0.92,P=0.034)。FB4-TBI组和FB4组在OS和NRM方面未观察到明显差异。本研究表明,在使用非亲属供体的MDS患者中,FB4加小剂量ATG方案可改善OS和NRM,但FB4加小剂量TBI方案与单用FB4相比无明显益处。
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引用次数: 0
Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma With Deletion 17p 17p缺失新诊断多发性骨髓瘤患者前期自体造血干细胞移植的实际效果
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.jtct.2024.10.011
Curtis Marcoux , Oren Pasvolsky , Denái R. Milton , Mark R. Tanner , Qaiser Bashir , Samer Srour , Neeraj Saini , Paul Lin , Jeremy Ramdial , Yago Nieto , Guilin Tang , Hans C. Lee , Krina K. Patel , Partow Kebriaei , Amna Ahmed , Yosra Aljawai , Sheeba K. Thomas , Robert Z. Orlowski , Elizabeth J. Shpall , Richard E. Champlin , Muzaffar H. Qazilbash
Despite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. The aim of this study was to evaluate real-world outcomes in patients with newly diagnosed MM (NDMM) with del(17p) undergoing upfront autologous hematopoietic stem cell transplantation (auto-HCT). We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being hematological response and measurable residual disease (MRD) status postauto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10–5 cells. One hundred and fifteen patients were included (55% male). Median age at auto-HCT was 62 years (range 34 to 83). The median del(17p) clone size was 20%, with 51 (53%) patients having clone sizes >20% and 15 (15%) patients having clone sizes >55%. Additional high-risk cytogenetic abnormalities included t(4;14) in 15 (13%) patients, t(14;16) in 8 (7%) patients, and 1q21+ in 25 (22%) patients. After induction, 10% of patients achieved ≥ CR, and 50% achieved ≥ VGPR, with 25% having MRD-negative ≥ VGPR. Post-transplant, 42% achieved ≥ CR, and 83% achieved ≥ VGPR as best response, with 55% (48/87) having MRD-negative ≥ VGPR. With a median follow-up of 31.4 months (range 3.1 to 199.1), median PFS and OS for the entire cohort were 19.9 and 71.5 months, respectively, and 5-year OS was 53%. Concurrent del(17p) and t(4;14) were associated with significantly worse outcomes, with median PFS and OS of 11.5 and 22.4 months, respectively. In multivariable analysis (MVA), female sex was associated with worse PFS (HR [95% CI] 2.87 [1.75 to 4.72], P < .001), while MRD negative CR post-transplant (0.35 [0.18 to 0.68], P = .002) and maintenance therapy (0.46 [0.27 to 0.77], P = 0.003) were associated with better PFS. In MVA for OS, female sex (2.22 [1.18 to 4.17], P = 0.013) and the presence of t(4;14) (2.55 [1.09 to 5.95], P = 0.030) were associated with worse OS, whereas Karnofsky Performance Status of ≥90 (0.47 [0.23 to 0.94], P = 0.034) was associated with better OS. This study affirms del(17p) as a high-risk abnormality with unfavorable outcomes despite modern therapies. The co-occurrence of del(17p) and t(4;14) was associated with particularly poor outcomes. Novel approaches are needed for this high-risk subgroup.
背景:尽管多发性骨髓瘤(MM)的治疗取得了巨大进步,但其预后仍不尽相同,在很大程度上受到临床和细胞遗传因素的影响。其中,17号染色体短臂缺失(del(17p))是预后不良的一个重要预测因素:本研究旨在评估新诊断的多发性骨髓瘤(NDMM)伴有del(17p)的患者接受前期自体血细胞移植的实际疗效:我们对2008年至2018年期间在MD安德森癌症中心接受前期自体血细胞移植的NDMM患者进行了单中心回顾性分析。主要终点为无进展生存期(PFS)和总生存期(OS),次要终点为自体血细胞移植后的血液学反应和最小残留病(MRD)状态。骨髓活检中的MRD状态采用8色新一代流式细胞术进行评估,灵敏度为1/10-5个细胞:结果:共纳入115名患者(55%为男性)。自体血细胞移植时的中位年龄为 62 岁(34-83 岁)。del(17p)克隆大小的中位数为20%,其中51例(53%)患者的克隆大小大于20%,15例(15%)患者的克隆大小大于55%。其他高风险细胞遗传学异常包括:15 例(13%)患者出现 t(4;14),8 例(7%)患者出现 t(14;16),25 例(22%)患者出现 1q21+。诱导治疗后,10%的患者达到≥CR,50%的患者达到≥VGPR,其中25%的患者MRD阴性≥VGPR。移植后,42%的患者达到≥CR,83%的患者达到≥VGPR的最佳反应,其中55%(48/87)的患者MRD阴性≥VGPR。中位随访时间为31.4个月(3.1-199.1个月),整个队列的中位PFS和OS分别为19.9个月和71.5个月,5年OS为53%。同时患有 del(17p) 和 t(4;14) 的患者预后明显较差,中位生存期和生存期分别为 11.5 个月和 22.4 个月。在患有 del(17p) 和 t(4;14)的亚组患者中,中位生存期和手术期分别为 11.5 个月和 22.4 个月。在多变量分析(MVA)中,女性性别与较差的 PFS 相关(HR [95% CI] 2.87 [1.75-4.72], p结论:本研究证实,尽管采用了现代疗法,del(17p)仍是一种对治疗结果不利的高危异常。del(17p)和t(4;14)同时出现与特别差的预后有关。对于这一高风险亚组,需要采用新的方法。
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引用次数: 0
Impact of the Type of Tyrosine Kinase Inhibitor (imatinib or dasatinib) Used Before allo-HCT on Outcome of Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia. A Study on Behalf of the Acute Leukemia Working Party of the EBMT 异基因造血干细胞移植前使用的酪氨酸激酶抑制剂(伊马替尼或达沙替尼)类型对费城阳性急性淋巴细胞白血病患者预后的影响。代表 EBMT 急性白血病工作组进行的一项研究。
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.jtct.2024.07.016
Sebastian Giebel , Myriam Labopin , Zinaida Peric , Jakob Passweg , Didier Blaise , Urpu Salmenniemi , David Beauvais , Péter Reményi , Patrice Chevallier , Stephan Mielke , Tobias Gedde-Dahl , Jan J. Cornelissen , Marie Balsat , Gesine Bug , Ali Bazarbachi , Eolia Brissot , Arnon Nagler , Fabio Ciceri , Mohamad Mohty
The use of tyrosine kinase inhibitors (TKIs) during induction and consolidation, followed by allogeneic hematopoietic cell transplantation (allo-HCT), is a standard of care for patients with Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL). The goal of this study was to compare results of allo-HCT according to the type of TKI used pre-transplant, either imatinib, dasatinib or both. This was a retrospective, registry-based analysis including adult patients with Ph-positive ALL treated with allo-HCT between years 2010-2022. The analysis included 606 patients pre-treated with imatinib, 163 with dasatinib and 94 with both imatinib and dasatinib. Allo-HCTs were performed in first complete remission from either unrelated (56%), matched sibling (36%) or haploidentical donors (8%). Relapse incidence at 2 years was 26% in the imatinib group and 21% in the dasatinib group and 19% in the imatinib + dasatinib group (P = .06) while non-relapse mortality was 19%, 15%, and 23%, respectively (P = .37). No significant differences were found for leukemia-free survival (55% vs. 63% vs. 58%, P = .11) and overall survival (72% vs. 76% vs. 65%, P = .32). The incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD was comparable across study groups, while the incidence of grade 3-4 acute GVHD was significantly increased for patients pre-treated with dasatinib alone (20%) than in the imatinib group (10%) or imatinib + dasatinib group (13%) (P = .002). On multivariate analysis a chance of GVHD and relapse-free survival (GRFS) was significantly decreased while the risk of grade 3-4 acute GVHD was increased for the dasatinib compared to imatinib group (hazard ratio, HR = 1.27, P = .048 and HR = 2.26, P = .0009, respectively). This study provides no evidence for the advantage of one TKI over another in terms of LFS and OS. However, the use of dasatinib is associated with increased risk of severe acute GVHD and decreased GRFS.
背景:在诱导和巩固治疗期间使用酪氨酸激酶抑制剂(TKIs),然后进行异基因造血细胞移植(allo-HCT),是费城(Ph)阳性急性淋巴细胞白血病(ALL)患者的标准治疗方法:本研究的目的是根据移植前使用的TKI类型(伊马替尼、达沙替尼或两者兼而有之)比较allo-HCT的结果:这是一项基于登记的回顾性分析,包括2010-2022年间接受allo-HCT治疗的Ph阳性ALL成人患者。分析包括606名接受伊马替尼预处理的患者、163名接受达沙替尼治疗的患者以及94名同时接受伊马替尼和达沙替尼治疗的患者。首次完全缓解的患者接受了异体供体移植,其中56%来自非亲属供体,36%来自配对同胞供体,8%来自单倍体供体:伊马替尼组、达沙替尼组和伊马替尼+达沙替尼组2年内的复发率分别为26%、21%和19%(P=0.06),而非复发死亡率分别为19%、15%和23%(P=0.37)。无白血病生存率(55% vs. 63% vs. 58%,p=0.11)和总生存率(72% vs. 76% vs. 65%,p=0.32)无明显差异。各研究组的2-4级急性移植物抗宿主疾病(GVHD)和慢性GVHD发生率相当,而单用达沙替尼预处理患者的3-4级急性GVHD发生率(20%)显著高于伊马替尼组(10%)或伊马替尼+达沙替尼组(13%)(p=0.002)。多变量分析显示,达沙替尼组与伊马替尼组相比,发生GVHD和无复发生存期(GRFS)的几率显著降低,而发生3-4级急性GVHD的风险增加(危险比分别为HR=1.27,p=0.048和HR=2.26,p=0.0009):本研究没有提供证据表明某种TKI比另一种TKI在LFS和OS方面更有优势。然而,使用达沙替尼与严重急性GVHD风险增加和GRFS下降有关。
{"title":"Impact of the Type of Tyrosine Kinase Inhibitor (imatinib or dasatinib) Used Before allo-HCT on Outcome of Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia. A Study on Behalf of the Acute Leukemia Working Party of the EBMT","authors":"Sebastian Giebel ,&nbsp;Myriam Labopin ,&nbsp;Zinaida Peric ,&nbsp;Jakob Passweg ,&nbsp;Didier Blaise ,&nbsp;Urpu Salmenniemi ,&nbsp;David Beauvais ,&nbsp;Péter Reményi ,&nbsp;Patrice Chevallier ,&nbsp;Stephan Mielke ,&nbsp;Tobias Gedde-Dahl ,&nbsp;Jan J. Cornelissen ,&nbsp;Marie Balsat ,&nbsp;Gesine Bug ,&nbsp;Ali Bazarbachi ,&nbsp;Eolia Brissot ,&nbsp;Arnon Nagler ,&nbsp;Fabio Ciceri ,&nbsp;Mohamad Mohty","doi":"10.1016/j.jtct.2024.07.016","DOIUrl":"10.1016/j.jtct.2024.07.016","url":null,"abstract":"<div><div>The use of tyrosine kinase inhibitors (TKIs) during induction and consolidation, followed by allogeneic hematopoietic cell transplantation (allo-HCT), is a standard of care for patients with Philadelphia (Ph)-positive acute lymphoblastic leukemia (ALL). The goal of this study was to compare results of allo-HCT according to the type of TKI used pre-transplant, either imatinib, dasatinib or both. This was a retrospective, registry-based analysis including adult patients with Ph-positive ALL treated with allo-HCT between years 2010-2022. The analysis included 606 patients pre-treated with imatinib, 163 with dasatinib and 94 with both imatinib and dasatinib. Allo-HCTs were performed in first complete remission from either unrelated (56%), matched sibling (36%) or haploidentical donors (8%). Relapse incidence at 2 years was 26% in the imatinib group and 21% in the dasatinib group and 19% in the imatinib + dasatinib group (<em>P = .</em>06) while non-relapse mortality was 19%, 15%, and 23%, respectively (<em>P = .</em>37). No significant differences were found for leukemia-free survival (55% vs. 63% vs. 58%, <em>P = .</em>11) and overall survival (72% vs. 76% vs. 65%, <em>P = .</em>32). The incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD was comparable across study groups, while the incidence of grade 3-4 acute GVHD was significantly increased for patients pre-treated with dasatinib alone (20%) than in the imatinib group (10%) or imatinib + dasatinib group (13%) (<em>P = .</em>002). On multivariate analysis a chance of GVHD and relapse-free survival (GRFS) was significantly decreased while the risk of grade 3-4 acute GVHD was increased for the dasatinib compared to imatinib group (hazard ratio, HR = 1.27, <em>P</em> = .048 and HR = 2.26, <em>P</em> = .0009, respectively). This study provides no evidence for the advantage of one TKI over another in terms of LFS and OS. However, the use of dasatinib is associated with increased risk of severe acute GVHD and decreased GRFS.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 14.e1-14.e10"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789116","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
Officers and Directors of ASTCT
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/S2666-6367(24)00820-0
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引用次数: 0
Novel Drug Combinations and Donor Lymphocyte Infusions Allow Prolonged Disease Control in Multiple Myeloma Patients Relapsing after Allogeneic Transplantation 多发性骨髓瘤患者在异体移植后复发的新疗法:多发性骨髓瘤患者在异体移植后复发的新疗法。
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.jtct.2024.10.015
Chiara Nozzoli , Martina Pucillo , Luisa Giaccone , Alessandro Rambaldi , Maria Teresa Lupo Stanghellini , Edoardo Benedetti , Domenico Russo , Nicola Mordini , Silvia Mangiacavalli , Paolo Bernasconi , Matteo Parma , Paola Carluccio , Piero Galieni , Paolo Rivela , Massimo Martino , Patrizia Chiusolo , Miriam Isola , Maria De Martino , Elena Oldani , Eliana Degrandi , Francesca Patriarca
<div><div>Although allogeneic stem cell transplantation (allo-SCT) is curative for only a minority of patients with multiple myeloma (MM), patients who relapse after allo-SCT can experience long-term survival, suggesting a synergy between antimyeloma drugs administered after allo-SCT and donor T cells. We retrospectively evaluated the outcome of MM patients reported to the Gruppo Italiano Trapianto Midollo Osseo e Terapia Cellulare (GITMO) network who underwent allo-SCT between 2009 and 2018, to identify predictors of long-term outcome in the whole population (242 patients) and predictors of prolonged overall survival (OS) after relapse in the subgroup of relapsed patients (118 patients). In the whole population, at a median follow-up of 40.9 months after allo-SCT, the median duration of OS and progression-free survival (PFS) were 39.4 and 19.0 months after allo-SCT, respectively. The cumulative incidence of nonrelapse mortality (NRM) was 10.3% at 1 year and 27.6% at 5 years. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 19.8%, and the 5-year cumulative incidence of moderate or severe chronic GVHD was 31.8%. In the multivariate model, older age at transplantation (<em>P</em> = .020), receipt of >2 lines of therapy before allo-SCT (<em>P</em> = .003), and transplantation from an unrelated or haploidentical donor (<em>P</em> = .025) were significant factors associated with reduced OS. Relapse after allo-SCT occurred in 118 patients (59%) at a median of 14.3 months (interquartile range, 7.2 to 26.9 months). Twenty patients (17%) received only steroids, radiotherapy, or supportive care; 41 (35%) received 1 line of salvage treatment; 23 (19%) received 2 lines of salvage treatment; and 34 (29%) received 3 or 4 lines of salvage treatment. Nine patients were treated exclusively with chemotherapy, 9 received at least 1 salvage treatment including immunomodulating agents, 43 patients were treated with at least 1 rescue therapy including proteasome inhibitors, and 37 patients received at least 1 salvage treatment including monoclonal antibodies (33 with daratumumab, 1 with elotuzumab, 1 with isatuximab, and 2 with belantamab). The median OS of relapsed patients was 38.5 months from allo-SCT and 20.2 months from relapse. In multivariate analysis, OS after relapse was significantly prolonged in patients with a longer time to relapse after allo-SCT (time to relapse 6 to 24 months, <em>P</em> = .016; time to relapse ≥24 months, <em>P</em> < .001) and in those who had received at least 3 lines of salvage treatment (<em>P</em> < .036) and donor lymphocyte infusion (DLI) (<em>P</em> = .020). In this study, patients who underwent transplantation in early phases of disease and with an HLA-identical sibling donor had the best chance of long-term survival. Late relapse after allo-SCT, multiple courses of salvage treatment, and an association with DLI could allow for long-term disease control in patients who experienced rel
背景:即使同种异体干细胞移植(allo-SCT)能治愈少数多发性骨髓瘤(MM)患者,但allo-SCT后复发的患者也能获得长期生存,这表明allo-SCT后服用的抗骨髓瘤药物与供体T细胞之间存在协同作用:我们回顾性评估了向 "Gruppo Italiano Trapianto Midollo Osseo e Terapia Cellulare"(GITMO)网络报告的、在2009年至2018年期间接受过异体造血干细胞移植的MM患者的预后,以确定全体患者(242例)的长期预后以及复发亚组患者(118例)的复发后总生存期(OS)延长的预测因素:结果:异体造血干细胞移植后的中位随访时间为40.9个月,整个人群的中位OS和无进展生存期(PFS)分别为39.4个月和19.0个月。非复发死亡率(NRM)的累积发生率(CI)在一年时为10.3%,五年时为27.6%。2-4级急性GVHD的CI为19.8%,中度或重度慢性GVHD的5年CI为31.8%。在多变量模型中,移植年龄较大(p=0.020)、异体造血干细胞移植前接受过两种以上的治疗(p=0.003)、非亲缘或单倍体供体移植(p=0.025)是降低OS的重要相关因素。118例(59%)患者在异体造血干细胞移植后复发,中位时间为14.3个月(IQR 7.2-26.9)。20名患者(17%)仅接受了类固醇、放疗或支持治疗,41名患者(35%)接受了1个疗程的治疗,23名患者(19%)接受了2个疗程的治疗,34名患者(29%)接受了3个或4个疗程的挽救治疗。9名患者只接受了化疗,9名患者接受了包括免疫调节剂(Imids)在内的至少一种挽救治疗,43名患者接受了包括蛋白酶体抑制剂(PIs)在内的至少一种挽救治疗,37名患者接受了包括单克隆抗体在内的至少一种挽救治疗(33种达拉单抗、1种艾洛妥珠单抗、1种异妥昔单抗、2种贝兰特单抗)。复发患者的中位生存期为异体造血干细胞移植后38.5个月,复发后20.2个月。在多变量分析中,同种异体移植后复发时间较长的患者(复发时间6-24个月,p=0.016;复发时间≥24个月,p< 0.001)和接受过至少3次挽救治疗的患者复发后的OS明显延长(p结论:在我们的研究中,在疾病的早期阶段进行移植并使用 HLA 相同的同胞供体的患者长期存活的机会最大。异体造血干细胞移植后晚期复发、多个疗程的挽救治疗以及与DLI的结合可使异体造血干细胞移植后复发的患者长期控制病情。
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引用次数: 0
Training in Transplantation and Cellular Therapy in Latin America: A Cross-Sectional Study of the LABMT 拉丁美洲的移植和细胞治疗培训:拉丁美洲移植和细胞治疗培训:LABMT 横向研究》:LABMT 调查。
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.jtct.2024.09.025
Andrés Noyola-Pérez , Rafaella Ribas-Muratori , Marco A. Vargas-Hernández , Laura Saavedra-Salazar , Cristóbal Frutos , Carmem Bonfim , Fernando Barroso-Duarte , Sebastián Galeano , Gregorio Jaimovich , Amado Karduss , Andrés Gómez-De León , Latin-American Bone Marrow Transplantation Group (LABMT)
Hematopoietic cell transplantation (HCT) is a complex and resource-intensive procedure that has become a critical treatment for certain hematologic conditions. However, in Latin America, access to HCT is limited compared to high-income countries, in part due to a lack of standardized training programs for HCT professionals. To address this gap, the Latin-American Bone Marrow Transplantation Group conducted a cross-sectional study to assess the current state of training programs in HCT and cellular therapy across the region. This study aimed to describe and analyze the availability, characteristics, and challenges of HCT training programs in Latin America, with a focus on identifying barriers and proposing solutions for improvement. A cross-sectional survey was sent to 127 recognized HCT centers across 14 Latin-American countries in December 2022. The survey collected data on institutional characteristics, training program structure, costs, and barriers to program development. Descriptive statistics were used to summarize the data, and comparative analyses were performed using Chi-square and Mann–Whitney tests. Of the 127 centers surveyed, 50 (39%) responded, with the majority located in Brazil (34%) and Mexico (30%). Among the respondents, 64% (n = 32) offered formal training programs lasting 6 months or longer. The most significant barriers reported were lack of funding (n = 21), limited number of transplant procedures (n = 15), and a shortage of qualified professors (n = 11). Proposed solutions included increasing student mobility opportunities (n = 28), enhancing program quality (n = 27), and improving access to funding (n = 15). Only 6% of programs offered exposure to CAR-T therapy, and fewer than half of the centers provided international rotations. This study highlights significant disparities in HCT training programs across Latin America, with most countries lacking access to formalized training. While Brazil and Mexico serve as regional hubs, other nations have limited or no training opportunities. Addressing these gaps through increased funding, international collaborations, and standardized curricula is essential to improving HCT training and ultimately patient care in the region.
背景:造血细胞移植(HCT)是一种复杂的资源密集型手术,已成为治疗某些血液病的重要方法。然而,在拉丁美洲,与高收入国家相比,获得造血干细胞移植的机会有限,部分原因是缺乏对造血干细胞移植专业人员的标准化培训计划。为弥补这一不足,拉丁美洲骨髓移植小组(LABMT)开展了一项横断面研究,以评估该地区造血干细胞移植和细胞疗法培训项目的现状:本研究旨在描述和分析拉丁美洲造血干细胞移植培训项目的可用性、特点和挑战,重点是找出障碍并提出改进方案:研究设计:2022 年 12 月,我们向 14 个拉美国家的 127 个公认的造血干细胞移植中心进行了横向调查。调查收集了有关机构特点、培训项目结构、成本和项目发展障碍的数据。采用描述性统计对数据进行总结,并使用卡方检验和曼-惠特尼检验进行比较分析:在接受调查的 127 家中心中,有 50 家(39%)做出了回应,其中大部分位于巴西(34%)和墨西哥(30%)。受访者中,64%(32 人)提供为期 6 个月或更长时间的正规培训计划。据报告,最主要的障碍是缺乏资金(21 人)、移植手术数量有限(15 人)和合格教授短缺(11 人)。建议的解决方案包括增加学生流动机会(人数=28)、提高项目质量(人数=27)和改善资金获取途径(人数=15)。只有6%的项目提供CAR-T疗法的接触机会,不到一半的中心提供国际轮转:本研究强调了拉丁美洲国家在 HCT 培训项目方面存在的巨大差异,大多数国家缺乏正规的培训机会。虽然巴西和墨西哥是地区中心,但其他国家的培训机会有限或根本没有。通过增加资金、国际合作和标准化课程来弥补这些差距,对于改善该地区的造血干细胞培训并最终改善患者护理至关重要。
{"title":"Training in Transplantation and Cellular Therapy in Latin America: A Cross-Sectional Study of the LABMT","authors":"Andrés Noyola-Pérez ,&nbsp;Rafaella Ribas-Muratori ,&nbsp;Marco A. Vargas-Hernández ,&nbsp;Laura Saavedra-Salazar ,&nbsp;Cristóbal Frutos ,&nbsp;Carmem Bonfim ,&nbsp;Fernando Barroso-Duarte ,&nbsp;Sebastián Galeano ,&nbsp;Gregorio Jaimovich ,&nbsp;Amado Karduss ,&nbsp;Andrés Gómez-De León ,&nbsp;Latin-American Bone Marrow Transplantation Group (LABMT)","doi":"10.1016/j.jtct.2024.09.025","DOIUrl":"10.1016/j.jtct.2024.09.025","url":null,"abstract":"<div><div>Hematopoietic cell transplantation (HCT) is a complex and resource-intensive procedure that has become a critical treatment for certain hematologic conditions. However, in Latin America, access to HCT is limited compared to high-income countries, in part due to a lack of standardized training programs for HCT professionals. To address this gap, the Latin-American Bone Marrow Transplantation Group conducted a cross-sectional study to assess the current state of training programs in HCT and cellular therapy across the region. This study aimed to describe and analyze the availability, characteristics, and challenges of HCT training programs in Latin America, with a focus on identifying barriers and proposing solutions for improvement. A cross-sectional survey was sent to 127 recognized HCT centers across 14 Latin-American countries in December 2022. The survey collected data on institutional characteristics, training program structure, costs, and barriers to program development. Descriptive statistics were used to summarize the data, and comparative analyses were performed using Chi-square and Mann–Whitney tests. Of the 127 centers surveyed, 50 (39%) responded, with the majority located in Brazil (34%) and Mexico (30%). Among the respondents, 64% (<em>n</em> = 32) offered formal training programs lasting 6 months or longer. The most significant barriers reported were lack of funding (<em>n</em> = 21), limited number of transplant procedures (<em>n</em> = 15), and a shortage of qualified professors (<em>n</em> = 11). Proposed solutions included increasing student mobility opportunities (<em>n</em> = 28), enhancing program quality (<em>n</em> = 27), and improving access to funding (<em>n</em> = 15). Only 6% of programs offered exposure to CAR-T therapy, and fewer than half of the centers provided international rotations. This study highlights significant disparities in HCT training programs across Latin America, with most countries lacking access to formalized training. While Brazil and Mexico serve as regional hubs, other nations have limited or no training opportunities. Addressing these gaps through increased funding, international collaborations, and standardized curricula is essential to improving HCT training and ultimately patient care in the region.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 1","pages":"Pages 47.e1-47.e9"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475655","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
Shift from Widespread to Tailored Antifungal Prophylaxis in Lymphoma Patients Treated with CD19 CAR T Cell Therapy: Results from a Large Retrospective Cohort 接受 CD19 CAR T 细胞疗法的淋巴瘤患者的抗真菌预防从广泛应用转向量身定制:大型回顾性队列的结果。
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.jtct.2024.10.010
Giovanna Melica , Alejandro Luna de Abia , Gunjan L. Shah , Sean Devlin , Magdalena Corona , Joshua Fein , Parastoo B. Dahi , Sergio A. Giralt , Richard J. Lin , M. Lia Palomba , Allison Parascondola , Jae Park , Gilles Salles , Amethyst Saldia , Michael Scordo , Roni Shouval , Miguel-Angel Perales , Susan K. Seo
Patients undergoing CD19 chimeric antigen receptor (CAR)–T cell therapy exhibit multiple immune deficits that may increase their susceptibility to infections. Invasive fungal infections (IFIs) are life-threatening events in the setting of hematologic diseases. However, there is ongoing debate regarding the optimal role and duration of antifungal prophylaxis in this specific patient population. The objective of this study was to provide a comprehensive overview of the evolution of IFI prophylactic strategies over time and to assess IFI incidence rates in a cohort of patients with relapsed or refractory (R/R) lymphoma treated with CAR-T cell therapy. A single-center retrospective study was conducted on a cohort of patients with R/R B cell lymphoma treated with CD19 CAR-T cell therapy between April 2016 and March 2023. Group A (April 2016–August 2020) consisted of patients primarily treated with fluconazole, irrespective of their individual IFI risk profile. In Group B (September 2020–March 2023) antifungal prophylaxis was recommended only for high-risk patients. Overall, 330 patients were included. Antifungal prophylaxis was prescribed to 119/142 (84%) patients in Group A and 58/188 (31%) in Group B (P < .001). Anti-mold azoles were prescribed to 8 (5.6%) patients in Group A and 21 (11.2%) patients in Group B. In Group A, 42 (29%) patients were switched to another antifungal, 9 (21%) because of toxicity, with 6 cases of transaminitis and 3 cases of prolonged QTc. In Group B, 21 (11.2%) patients were switched to the antifungal drug, mainly from fluconazole or micafungin to a mold-active agent following revised guidelines. No difference was found in liver toxicity between the two groups at infusion, day 10, and day 30. No significant differences were observed between the groups. IFIs following CAR-T cell therapy were rare, with 1 case of cryptococcal meningoencephalitis in group A (.7%) and 1 case of invasive aspergillosis in Group B (.5%), both occurring in patients on micafungin prophylaxis. In this large single-center cohort of patients with R/R lymphoma treated with CAR-T cells, we show that individualized prophylaxis, alongside careful management of CAR-T cell–related toxicities such as CRS, was associated with a very low IFI rate, avoiding the risk of unnecessary toxicities, drug–drug interactions, and high costs.
背景:接受 CD19 嵌合抗原受体(CAR)T 细胞疗法的患者表现出多种免疫缺陷,这可能会增加他们对感染的易感性。侵袭性真菌感染(IFI)是血液病中威胁生命的疾病。然而,关于抗真菌预防在这一特殊患者群体中的最佳作用和持续时间一直存在争议:本研究的目的是全面概述随着时间推移IFI预防策略的演变,并评估接受CAR-T细胞疗法治疗的复发或难治性(R/R)淋巴瘤患者队列中的IFI发生率:2016年4月至2023年3月期间接受CD19 CAR-T细胞疗法治疗的R/R B细胞淋巴瘤患者队列的单中心回顾性研究。A组(2016年4月至2020年8月)包括主要接受氟康唑治疗的患者,无论其个体IFI风险状况如何。B 组(2020 年 9 月至 2023 年 3 月)仅建议高风险患者使用抗真菌预防:结果:共纳入 330 名患者。A组有119/142(84%)名患者接受了抗真菌预防治疗,B组有58/188(31%)名患者接受了抗真菌预防治疗:在这个大型单中心队列中,我们对接受CAR T细胞治疗的R/R淋巴瘤患者进行了研究,结果表明,在谨慎处理CAR T细胞相关毒性(如CRS)的同时,个体化预防与极低的IFI率相关,避免了不必要的毒性、药物间相互作用和高成本风险。
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引用次数: 0
Representativeness of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Trial Participants 血液和骨髓移植临床试验网络 (BMT CTN) 试验参与者的代表性。
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.jtct.2024.10.014
Manmeet Kaur , Mary M. Horowitz , Adam Mendizabal , Min Chen , Amy Foley , Jeffery J. Auletta , Steven Devine , Anita D'Souza
Underrepresentation by race and ethnicity in oncology clinical trials, including those of hematopoietic cell transplantation (HCT), is a known challenge. This analysis studied accrual on Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials conducted in 2014 to 2020 by race/ethnicity, age, and sex, comparing these characteristics with those of potentially eligible patients identified from the Surveillance, Epidemiology, and End Results (SEER) and Center for International Blood and Marrow Transplant Research (CIBMTR) databases for the disease, age, and years of interest of BMT CTN studies. Five BMT CTN trials met the inclusion criteria, including 1 autologous HCT trial and 4 allogeneic HCT trials. Two studies focused on multiple myeloma (BMT CTN 1302 and 1401), 2 studies focused on graft-versus-host disease (GVHD) treatment (BMT CTN 1301 and 1501), and 1 study focused on post-HCT maintenance therapy in FLT3+ acute myelogenous leukemia (BMT CTN 1506). A decline in the proportion of patients from minority racial and ethnic groups was seen from the SEER population to trial enrollees, with the largest drop seen between the SEER population and all patients who underwent HCT (on or off trial) at US transplant centers. Allogeneic HCT trials that allowed alternative donor graft sources had less decrease from the SEER population. No decrease in clinical trial enrollment was seen with respect to older age and female HCT recipients. This study provides insight into the underrepresentation of racial and ethnic minority patients in BMT CTN clinical trials, owing largely to lack of access to HCT in general. Pathways expanding access to donors and improving the outreach of HCT programs to underserved populations are needed to improve access to clinical trials.
在包括造血细胞移植(HCT)在内的肿瘤临床试验中,种族和民族代表性不足是一个众所周知的挑战。这项分析研究了2014-20年开展的血液和骨髓移植临床试验网络(BMT CTN)试验中按种族/人种、年龄和性别分列的应计人数,并将这些特征与SEER和CIBMTR数据库中针对BMT CTN研究的疾病、年龄和年份确定的潜在合格患者的特征进行了比较。有五项 BMT CTN 试验符合纳入标准,其中包括一项自体 HCT 试验和四项异体 HCT 试验。两项研究的重点是多发性骨髓瘤(BMT CTN 1302 和 1401),两项研究的重点是移植物抗宿主疾病(GVHD)治疗(BMT CTN 1301 和 1501),一项研究的重点是 FLT3+ 急性髓性白血病的 HCT 后维持治疗(BMT CTN 1506)。从 SEER 人群到参加试验的患者中,少数种族和族裔群体患者的比例有所下降,其中 SEER 人群与美国移植中心的所有移植患者(试验中或试验外)之间的比例下降幅度最大。允许替代供体移植来源的异体造血干细胞移植试验与 SEER 群体相比下降幅度较小。年龄较大和女性接受造血干细胞移植者的临床试验注册人数没有减少。这项研究深入揭示了少数种族和少数族裔患者在 BMT CTN 临床试验中代表性不足的问题,这主要是由于缺乏获得造血干细胞移植的途径。要提高临床试验的可及性,就必须扩大捐献者的获取途径,并改善造血干细胞项目对服务不足人群的外联工作。
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引用次数: 0
Challenging the Status Quo: Multi-level Solutions for Equitable Hematopoietic Cell Transplantation Clinical Trial Representation 挑战现状:公平的造血细胞移植临床试验代表性的多层次解决方案。
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.jtct.2024.12.014
Kristine A. Karvonen
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引用次数: 0
Profile of a Pioneer: Eliane Gluckman 先驱者简介:Eliane Gluckman。
IF 3.6 3区 医学 Q2 HEMATOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.jtct.2024.12.012
Joanne Kurtzberg
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引用次数: 0
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Transplantation and Cellular Therapy
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