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Single-Agent Cyclosporine for Graft-versus-Host Disease Prophylaxis in Patients with Acquired Aplastic Anemia Receiving Fludarabine-Based Conditioning 单药环孢素在接受氟达拉滨为基础的治疗的获得性再生障碍性贫血患者中的移植物抗宿主病预防
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.07.026
Raheel Iftikhar , Qamar un Nisa Chaudhry , Syed Kamran Mahmood , Tariq Ghafoor , Humayun Shafique Satti , Nighat Shahbaz , Mehreen Ali Khan , Tariq Azam Khattak , Ghassan Umair Shamshad , Jahanzeb Rehman , Muhammad Farhan , Saima Humayun , Amina Risalat , Ahsan Wahab , Tariq Mehmood Satti , Faiz Anwer , Parvez Ahmed

Cyclosporine (CsA) combined with short-course methotrexate is considered standard-of-care graft-versus-host disease (GVHD) prophylaxis for patients with severe aplastic anemia (AA) who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu)-based conditioning. We conducted a single-center retrospective analysis of patients with acquired AA (n = 106) undergoing MRD transplantation from July 2007 through January 2019. All patients received Flu-Cy-ATG conditioning and single-agent CsA as GVHD prophylaxis. Median age of the study cohort was 20 years (range, 3 to 52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range, 2.8 to 62). Graft source was bone marrow harvest in 71 (68%), combined bone marrow and peripheral blood stem cells in 34 (31%), and peripheral blood alone in 1 (1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% confidence interval [CI], 87.3% to 97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI, 84% to 96%). Cumulative incidence of primary graft failure at day 28 was 6.6% (95% CI, 4% to 8%) while secondary graft failure occurred at a median of 190 days (range, 90 to 415) at a cumulative incidence of 3.7% (95% CI, 2% to 5%). Cumulative incidence of grade II to IV acute GVHD at day 100 was 3.8% (95% CI, 1.4% to 9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI, 2.6% to 15%). Median follow-up post-transplant was 61 months (range, 6 to 144). Overall survival was 84.9%, disease-free survival was 80.2%, and GVHD-free relapse-free survival was 76.3%. This study indicates that single-agent cyclosporine is a feasible option for GVHD prophylaxis in MRD hematopoietic stem cell transplantation using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD.

环孢素(CsA)联合短期甲氨蝶呤被认为是严重再生障碍性贫血(AA)患者使用环磷酰胺(Cy)加抗胸腺细胞球蛋白(ATG)进行移植的标准治疗移植物抗宿主病(GVHD)预防。然而,对于接受匹配相关供体(MRD)移植的患者使用氟达拉滨(Flu)为基础的调节,移植后GVHD的最佳预防措施尚无共识。我们对2007年7月至2019年1月接受MRD移植的获得性AA患者(n = 106)进行了单中心回顾性分析。所有患者均接受流感- cy - atg调节和单药CsA作为GVHD预防。研究队列的中位年龄为20岁(范围3 - 52岁),男女比例为3.8:1。从诊断到移植的中位时间为11.5个月(范围:2.8 - 62)。移植来源为骨髓71例(68%),骨髓和外周血干细胞联合34例(31%),单独外周血1例(1%)。第28天中性粒细胞植入的累积发生率为93.4%(95%可信区间[CI], 87.3% ~ 97.1%),第100天血小板植入的累积发生率为90.5% (95% CI, 84% ~ 96%)。第28天原发性移植物衰竭的累积发生率为6.6% (95% CI, 4%至8%),而继发性移植物衰竭发生在中位190天(范围,90至415),累积发生率为3.7% (95% CI, 2%至5%)。在第100天,II至IV级急性GVHD的累积发病率为3.8% (95% CI, 1.4%至9.9%),而慢性GVHD的1年概率为7.5% (95% CI, 2.6%至15%)。移植后中位随访时间为61个月(6 ~ 144个月)。总生存率为84.9%,无病生存率为80.2%,无gvhd无复发生存率为76.3%。该研究表明,单药环孢素是使用流感- cy - atg调节的MRD造血干细胞移植中预防GVHD的可行选择,并且与非常低的急性和慢性GVHD发生率相关。
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引用次数: 1
The Effect of Granulocyte Colony-Stimulating Factor Use on Hospital Length of Stay after Allogeneic Hematopoietic Cell Transplantation: A Retrospective Multicenter Cohort Study 粒细胞集落刺激因子对异基因造血细胞移植术后住院时间的影响:一项回顾性多中心队列研究
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.013
Gemlyn George , Andrew St. Martin , Saurabh Chhabra , Mary Eapen

Granulocyte colony-stimulating factor (G-CSF) is administered after allogeneic hematopoietic cell transplantation (HCT) to aid neutrophil recovery. We compared the effect of empiric G-CSF administration on the duration of index inpatient hospitalization stay after HCT for patients aged ≥18 years with a hematologic malignancy. G-CSF was considered empiric if administered between day -3 and day +6 in relation to graft infusion. We studied 3562 HCTs (1487 HLA-matched sibling donor HCTs and 2075 HLA-matched unrelated donor HCTs) between 2007 and 2016. Three hundred and thirteen (21%) recipients of HLA-matched sibling donor HCT and 417 (20%) recipients of HLA-matched unrelated donor HCT received empiric G-CSF therapy. The effect of G-CSF therapy on the index hospitalization stay was examined in generalized linear models (GLMs) with adjustment for other patient, disease, and transplantation characteristics and acute graft-versus-host disease and infection post-transplantation. The duration of index hospitalization by treatment group did not differ for HLA-matched sibling donor HCT but was shorter with G-CSF for HLA-matched unrelated donor HCT (15 days versus 19 days; P < .001). Our GLMs confirmed shorter hospitalization with the use of G-CSF therapy for HLA-matched unrelated donor HCT (P = .01). G-CSF therapy was not associated with early survival for either donor type, and there was no benefit or disadvantage of giving G-CSF to promote neutrophil recovery.

同种异体造血细胞移植(HCT)后给予粒细胞集落刺激因子(G-CSF)以帮助中性粒细胞恢复。我们比较了经验性G-CSF给药对年龄≥18岁的血液恶性肿瘤患者HCT后指数住院时间的影响。如果在移植物输注的第3天和第6天之间给予G-CSF,则被认为是经验性的。我们在2007年至2016年间研究了3562例hct(1487例hla匹配的兄弟姐妹供体hct和2075例hla匹配的非亲属供体hct)。313名(21%)hla匹配的兄弟姐妹HCT受者和417名(20%)hla匹配的非亲属HCT受者接受了经验性G-CSF治疗。采用广义线性模型(GLMs)检验G-CSF治疗对指数住院时间的影响,并对其他患者、疾病和移植特征以及移植后的急性移植物抗宿主病和感染进行调整。治疗组间的指数住院时间对于hla匹配的兄弟姐妹供体HCT没有差异,但对于hla匹配的非亲属供体HCT, G-CSF的住院时间较短(15天对19天;P & lt;措施)。我们的GLMs证实,使用G-CSF治疗hla匹配的非亲属供体HCT患者住院时间缩短(P = 0.01)。G-CSF治疗与两种供体类型的早期生存无关,给予G-CSF促进中性粒细胞恢复无利或弊。
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引用次数: 3
Response to Letter to Editor Regarding “Comparing Efficacy, Safety, and Preinfusion Period of Axicabtagene Ciloleucel versus Tisagenlecleucel in Relapsed/Refractory Large B Cell Lymphoma” 关于“比较阿西卡他格西洛鲁与Tisagenlecleucel治疗复发/难治性大B细胞淋巴瘤的疗效、安全性和预输注时间”的回复
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.09.009
Olalekan O. Oluwole , Jeroen P. Jansen , Vincent W. Lin , Keith Chan , Sam Keeping , Lynn Navale , Frederick L. Locke
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引用次数: 3
Costs of Cord Blood Transplantation Are Higher Than Other Graft Sources in Patients with Acute Leukemia and Myelodysplastic Syndrome Treated at Pediatric Centers 在儿科中心治疗急性白血病和骨髓增生异常综合征的患者,脐带血移植的费用高于其他移植来源
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.09.011
Hemalatha G. Rangarajan , Joseph R. Stanek , Rolla Abu-Arja

In this commentary, we discuss the reasons why umbilical cord blood (UCB) allogeneic stem cell transplants are more expensive than matched related and matched unrelated peripheral blood and bone marrow transplants in patients treated at pediatric centers. We compare results of our previously published study with the recently published study from the Center for International Bone Marrow Transplant and Research/Pediatric Health Information System and also highlight the factors that contribute to increased costs of UCB transplants.

在这篇评论中,我们讨论了在儿科中心治疗的患者中,脐带血(UCB)异体干细胞移植比匹配的相关和匹配的非相关外周血和骨髓移植更昂贵的原因。我们将我们之前发表的研究结果与国际骨髓移植和研究中心/儿科健康信息系统最近发表的研究结果进行了比较,并强调了导致UCB移植成本增加的因素。
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引用次数: 1
Australasian Trends in Allogeneic Stem Cell Transplantation for Myelofibrosis in the Molecular Era: A Retrospective Analysis from the Australasian Bone Marrow Transplant Recipient Registry 分子时代澳大利亚同种异体干细胞移植治疗骨髓纤维化的趋势:来自澳大利亚骨髓移植接受者登记的回顾性分析
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.024
Yadanar Lwin , Glenn Kennedy , David Gottlieb , John Kwan , David Ritchie , Jeff Szer , Samuel Milliken , Peter Browett , Andrew Spencer , Andrew Butler , Peter Bardy , Matthew Greenwood , Travis Perera , Simon He , Ashley McEwan , Stephen Larsen , Hock Lai , Duncan Purtill , Steven Tran , Donna Aarons , Nada Hamad

To review the updated trends of national practice and outcomes in transplantation to treat myelofibrosis (MF), we retrospectively evaluated 142 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) for primary (n = 94) or secondary (n = 48) MF at an Australian/New Zealand transplantation center between 2006 and 2017. The median duration of follow-up was 51.8 months (range, 3.1 to 148 months). The median age at allo-HSCT was 56 years (range, 26 to 69 years). Fifty-two percent of the patients had HLA-identical sibling donors, and 45% had matched unrelated donors (UD). Conditioning regimens were predominantly reduced intensity (83%). Before transplantation, 16% of the patients had undergone splenectomy or splenic irradiation, and 38% (n = 54) received JAK inhibitor therapy. JAK2 mutation testing was performed in 66.9% of the patients, whereas other mutations (CALR, MPL, ASXL1, SRSF2, U2AF1Q57, EZH2, and IDH1/2) were rarely tested (1.4% to 8.4%). Only 4.2% of patients had next-generation sequencing mutation analysis. The median time to neutrophil engraftment was 19 days (range, 10 to 43 days), and the median time to platelet engraftment was 27 days (range, 13 to 230 days). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 21.4% at 100 days, and that of extensive chronic GVHD (cGVHD) at 5 years was 18.1%. Overall survival (OS) was 67% at 1 year and 57% at 5 years. GVHD-free, relapse-free survival was 54% at 1 year and 42% at 5 years. The cumulative incidence of nonrelapse mortality (NRM) was 16% at 100 days and 25% at 1 year. In multivariate analysis, age ≥65 years and use of an UD were identified as significant unfavorable risk factors for OS and NRM. Use of an UD increased the incidence of aGVHD, whereas administration of antithymocyte globulin/alemtuzumab lowered the risk of both aGVHD and cGVHD. Pretransplantation splenectomy/splenic irradiation had a positive influence on time to engraftment. There have been no improvements in the outcomes of allo-HSCT for MF in Australasia over the last decade, with a low uptake of molecular genomic technology due to limited access to funding.

为了回顾移植治疗骨髓纤维化(MF)的国家实践和结果的最新趋势,我们回顾性评估了2006年至2017年间在澳大利亚/新西兰移植中心接受同种异体造血干细胞移植(alloc - hsct)治疗原发性(n = 94)或继发性(n = 48) MF的142例患者。中位随访时间为51.8个月(范围3.1 ~ 148个月)。同种异体造血干细胞移植的中位年龄为56岁(范围为26至69岁)。52%的患者有相同的hla兄弟姐妹供体,45%有匹配的非亲属供体(UD)。调理方案主要是降低强度(83%)。在移植前,16%的患者接受了脾切除术或脾照射,38% (n = 54)接受了JAK抑制剂治疗。66.9%的患者进行了JAK2突变检测,而其他突变(CALR、MPL、ASXL1、SRSF2、U2AF1Q57、EZH2和IDH1/2)很少进行检测(1.4%至8.4%)。只有4.2%的患者进行了下一代测序突变分析。中性粒细胞移植的中位时间为19天(范围10 ~ 43天),血小板移植的中位时间为27天(范围13 ~ 230天)。II-IV级急性移植物抗宿主病(aGVHD)的累积发病率在100天时为21.4%,在5年时广泛慢性移植物抗宿主病(cGVHD)的累积发病率为18.1%。总生存率(OS) 1年67%,5年57%。1年无gvhd、无复发生存率为54%,5年为42%。累计非复发死亡率(NRM)在100天时为16%,在1年时为25%。在多变量分析中,年龄≥65岁和使用UD被确定为OS和NRM的显著不利危险因素。使用UD会增加aGVHD的发生率,而使用抗胸腺细胞球蛋白/阿仑单抗可降低aGVHD和cGVHD的风险。移植前脾切除术/脾照射对移植时间有积极影响。在过去的十年里,由于资金有限,分子基因组技术的使用率很低,澳大利亚的同种异体造血干细胞移植治疗MF的结果没有任何改善。
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引用次数: 8
BEAM-Campath Allogeneic Stem Cell Transplant for Patients with Relapsed/Refractory Lymphoma: High Incidence of Long-Term Mixed Donor-Recipient Chimerism and the Response to Donor Lymphocyte Infusions BEAM-Campath同种异体干细胞移植治疗复发/难治性淋巴瘤:长期混合供体-受体嵌合的高发率和供体淋巴细胞输注的反应
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.028
Claire Burney , Karan Wadhera , Patricia Breslin , Rachel Pearce , Matthew Wells , Rajesh Alajangi , Rachel Protheroe , David I. Marks , James Griffin , Stephen Robinson

BiCNU (carmustine), etoposide, Ara-C, melphalan (BEAM) and Campath conditioning was developed to reduce the high transplant-related mortality in patients with lymphoma while delivering intensive antilymphoma immunotherapy, as well as to some extent a platform for allogeneic stem cell engraftment. Significant numbers of patients appeared to have persistent recipient-derived hematopoiesis, and therefore we retrospectively analyzed patients with lymphoma undergoing BEAM-Campath conditioned allogeneic stem cell transplantation at our center (2003 to 2017) to characterize the patterns of chimerism and patient outcomes. Chimerism was analyzed with short tandem repeat PCR. Mixed donor-recipient chimerism (MDRC) was defined as 5% to 94.9% donor. Fifty-two patients (n = 30 male), with a median age of 45 years, were identified with histologic diagnoses of Hodgkin lymphoma (n = 13), diffuse large B cell lymphoma (n = 7), low-grade non-Hodgkin lymphoma (n = 16), mantle cell lymphoma (n = 10), and T cell lymphoma (n = 6). Pretransplant, 93% achieved complete response (52%) or partial response (41%) with a median of 3 prior therapies (n = 3 prior autologous stem cell transplantation). Donors were Matched sibling donors (MSD) (n = 21), matched unrelated donors (MUD) (n = 24), miss-matched unrelated donors (MMUD) (n = 6), and syngeneic (n = 1). Acute graft-versus host disease (GVHD) developed in 52% (81% grade I to II) and chronic GVHD (83% extensive) in 12%. MDRC of T cells (MDRCt) developed in 62% (n = 32), and 29% (n = 15) developed MDRC of myeloid cells (MDRCm) at a median onset of 100 days. Donor lymphocyte infusion (DLI) was given to 17 patients, with a median starting dose of 1 × 106/kg. The first DLI was given at a median of 225 days post-transplant (range, 99 days to 5.3 years). Of these, 9 developed acute post-DLI GVHD and 2 limited chronic GVHD. Conversion to full donor occurred in 47% MDRCt and 50% MDRCm. Multivariate analysis identified sibling donor type as associated with increased MDRCt (P = .035; hazard ratio [HR], 0.17) and reduced total nucleated cell dose with increased MDRCm (P = .021; HR, 0.76). The median follow-up was 6 years, and 2-year NRM cumulative incidence was 16% (95% confidence interval [CI], 7% to 27%). Ten-year progression and extensive GVHD-free survival was 45% (95% CI, 28% to 61%), and overall survival was 66% (95% CI, 50% to 78%). One-year landmark analysis identified no increased GVHD or relapse risk with MDRCt or MDRCm but reduced nonrelapse mortality (NRM) risk with MDRCt (P = .001). BEAM-Campath allografts for high-risk lymphoma achieve long-term disease-free survival with low rates of GVHD and transplant-related mortality. The frequent development of myeloid MDRC demonstrates that BEAM-Campath is a nonmyeloablative conditioning regimen in almost a third of patients. MDRCt is associated with reduced NRM, but neither MDRCt or MDRCm is associated with increased

BiCNU (carmustine)、依托泊苷(etoposide)、Ara-C、melphalan (BEAM)和Campath调节剂的开发是为了降低淋巴瘤患者移植相关的高死亡率,同时提供强化抗淋巴瘤免疫治疗,并在一定程度上为异体干细胞移植提供平台。大量患者似乎具有持续的受体来源造血功能,因此我们回顾性分析了2003年至2017年在我们中心接受BEAM-Campath条件异体干细胞移植的淋巴瘤患者,以表征嵌合模式和患者结局。用短串联重复PCR分析嵌合现象。混合供受体嵌合(MDRC)定义为5%至94.9%的供体。52例患者(n = 30名男性),中位年龄45岁,组织学诊断为霍奇金淋巴瘤(n = 13),弥漫性大B细胞淋巴瘤(n = 7),低级别非霍奇金淋巴瘤(n = 16),套细胞淋巴瘤(n = 10)和T细胞淋巴瘤(n = 6)。移植前,93%的患者获得完全缓解(52%)或部分缓解(41%),中位既往治疗3次(n = 3次既往自体干细胞移植)。供体包括匹配的兄弟姐妹供体(MSD) (n = 21)、匹配的非亲属供体(MUD) (n = 24)、不匹配的非亲属供体(MMUD) (n = 6)和同基因供体(n = 1)。52%(81%为I至II级)发生急性移植物抗宿主病(GVHD), 12%发生慢性GVHD(83%为广泛)。62% (n = 32)的患者出现T细胞MDRC (MDRCt), 29% (n = 15)的患者出现髓样细胞MDRC (MDRCm),发病时间中位数为100天。17例患者给予供体淋巴细胞输注(DLI),起始中位剂量为1 × 106/kg。第一次DLI是在移植后225天(99天至5.3年)给予的。其中9例发展为急性GVHD, 2例发展为有限的慢性GVHD。47%的MDRCt和50%的MDRCm转为完全供者。多因素分析发现,兄弟姐妹供体类型与MDRCt增加有关(P = 0.035;风险比[HR], 0.17),随着MDRCm的增加,有核细胞总剂量降低(P = 0.021;人力资源,0.76)。中位随访时间为6年,2年NRM累计发生率为16%(95%可信区间[CI], 7%至27%)。十年进展和广泛无gvhd生存率为45% (95% CI, 28%至61%),总生存率为66% (95% CI, 50%至78%)。一年的里程碑式分析发现,MDRCt或MDRCm没有增加GVHD或复发风险,但MDRCt降低了非复发死亡率(NRM)风险(P = 0.001)。BEAM-Campath同种异体移植治疗高风险淋巴瘤可实现长期无病生存,GVHD发生率低,移植相关死亡率低。髓系MDRC的频繁发展表明BEAM-Campath在近三分之一的患者中是非清髓性调节方案。MDRCt与NRM降低相关,但MDRCt或MDRCm均与GVHD增加或复发无关。
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引用次数: 2
The Global State of Hematopoietic Cell Transplantation for Multiple Myeloma: An Analysis of the Worldwide Network of Blood and Marrow Transplantation Database and the Global Burden of Disease Study 多发性骨髓瘤的全球造血细胞移植状况:对全球血液和骨髓移植数据库网络和全球疾病负担研究的分析
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.018
Andrew J. Cowan , Helen Baldomero , Yoshiko Atsuta , Joseph Mikhael , Mahmoud Aljurf , Adriana Seber , Hildegard Greinix , Mickey Koh , Nina Worel , Edward N. Libby , Marcelo Pasquini , Sebastian Galeano , Wael Saber , Minako Iida , Gregorio Jaimovich , Juliana Martinez Rolon , Yoshihisa Kodera , Malek Benakli , Bazuaye G. Nosa , Alaa Elhaddad , Dietger Niederwieser

Multiple myeloma (MM) is a plasma cell neoplasm characterized by destructive bony lesions, anemia, and renal impairment. Access to effective therapy is limited globally. We report the rates and utilization of hematopoietic cell transplantation (HCT) globally from 2006-2015 to better characterize access to HCT for patients with MM.

This was an analysis of a retrospective survey of Worldwide Network of Blood and Marrow Transplant sites, conducted annually between 2006-2015. Incidence estimates were from the Global Burden of Disease study. Outcome measures included total number of autologous and allogeneic HCTs by world regions, and percentage of newly diagnosed MM patients who underwent HCT, calculated by the number of transplants per region in calendar year/gross annual incidence of MM per region.

From 2006 to 2015, the number of autologous HCT performed worldwide for MM increased by 107%. Utilization of autologous HCT was highest in Northern America and European regions, increasing from 13% to 24% in Northern America, and an increase from 15% to 22% in Europe. In contrast, the utilization of autologous HCT was lower in the Africa/Mediterranean region, with utilization only changing from 1.8% in 2006 to 4% in 2015. The number of first allogeneic HCT performed globally for MM declined after a peak in 2012 by -3% since 2006.

Autologous HCT utilization for MM has increased worldwide in high-income regions but remains poorly utilized in Africa and the East Mediterranean. More work is needed to improve access to HCT for MM patients, especially in low to middle income countries.

© 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

多发性骨髓瘤(MM)是一种浆细胞肿瘤,其特征为破坏性骨病变、贫血和肾损害。在全球范围内,获得有效治疗的机会有限。我们报告了2006-2015年全球造血细胞移植(HCT)的使用率和利用率,以更好地描述mm患者获得HCT的情况。这是对2006-2015年间每年进行的全球血液和骨髓移植网站网络回顾性调查的分析。发病率估计来自全球疾病负担研究。结果测量包括世界各地区自体和异体HCT的总数,以及新诊断的MM患者接受HCT的百分比,计算方法为历年每个地区的移植数量/每个地区MM的年总发病率。从2006年到2015年,全球MM自体HCT数量增加了107%。自体HCT的使用率在北美和欧洲地区最高,在北美从13%增加到24%,在欧洲从15%增加到22%。相比之下,非洲/地中海地区的自体HCT使用率较低,使用率仅从2006年的1.8%变化到2015年的4%。全球首例同种异体HCT治疗的数量在2012年达到高峰后,自2006年以来下降了-3%。自体HCT治疗MM的使用率在全球高收入地区有所增加,但在非洲和东地中海使用率仍然很低。需要做更多的工作来改善MM患者获得HCT的机会,特别是在低收入和中等收入国家。©2020美国移植和细胞治疗学会。Elsevier Inc.出版。
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引用次数: 17
A New Standard in Graft-versus-Host Disease Prophylaxis? An Introduction to Blood and Marrow Transplant Clinical Trials Network 1703 预防移植物抗宿主病的新标准?血液和骨髓移植临床试验网络简介
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.029
Zachariah DeFilipp , Linda J. Burns , Samantha M. Jaglowski , Aaron L. Leppin , Steven Pavletic , Bryce Waldman , Daniel J. Weisdorf , William A. Wood , Nandita Khera

Effective immunosuppressive regimens to prevent the development of graft-versus-host disease (GVHD) are essential to the success of allogeneic hematopoietic cell transplantation (HCT). After revolutionizing haploidentical transplantation, post-transplantation cyclophosphamide (PTCy) is now being evaluated for HCT performed from related and unrelated donors. In this setting, 2 recent randomized studies have demonstrated lower rates of GVHD and superior GVHD-free, relapse-free survival with PTCy compared with conventional GVHD prophylaxis. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) is currently conducting a large, randomized phase III, multicenter trial (BMT CTN 1703) comparing PTCy/tacrolimus/mycophenolate mofetil to tacrolimus/methotrexate as GVHD prophylaxis regimens in reduced-intensity allogeneic HCT. Here we review the ongoing study, highlight its importance to the field, and explore the possible implications of its results on clinical practice.

有效的免疫抑制方案以防止移植物抗宿主病(GVHD)的发展是成功的同种异体造血细胞移植(HCT)的关键。在单倍体移植发生革命性变化后,移植后环磷酰胺(PTCy)目前正被用于亲属和非亲属供体HCT的评估。在这种情况下,最近的两项随机研究表明,与传统的GVHD预防相比,PTCy治疗的GVHD发生率更低,无GVHD、无复发生存率更高。血液和骨髓移植临床试验网络(BMT CTN)目前正在进行一项大型随机III期多中心试验(BMT CTN 1703),比较PTCy/他克莫司/霉酚酸酯与他克莫司/甲氨蝶呤作为GVHD预防方案在低强度同种异体HCT中的应用。在这里,我们回顾正在进行的研究,强调其对该领域的重要性,并探讨其结果对临床实践的可能影响。
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引用次数: 2
Prognostic Impact of Cytogenetic Evolution on the Outcome of Allogeneic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia in Nonremission: A Single-Institute Analysis of 212 Recipients 细胞遗传进化对急性髓系白血病非缓解患者同种异体干细胞移植预后的影响:一项对212名受者的单研究所分析
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.08.026
Mitsuhiro Yuasa , Hisashi Yamamoto , Takashi Mitsuki , Kosei Kageyama , Daisuke Kaji , Yuki Taya , Aya Nishida , Kazuya Ishiwata , Shinsuke Takagi , Go Yamamoto , Yuki Asano-Mori , Atsushi Wake , Yukako Koike , Shigeyoshi Makino , Naoyuki Uchida , Shuichi Taniguchi

Recent progress in genetic analysis technology has helped researchers understand the pathogenesis of acute myeloid leukemia (AML). Considering this progress, AML karyotype is still one of the most significant prognostic factors that provides risk-adapted treatment approaches. Karyotype changes during treatment have been observed at times, but their prognostic impact is sparse, especially on allogeneic stem cell transplantation (allo-SCT). Here, we retrospectively investigated the effect of chromosomal changes between diagnosis and pretransplantation on the prognosis of allo-SCT by analyzing the outcomes of 212 consecutive patients who underwent allo-SCT for the first time at Toranomon Hospital, Tokyo, Japan, between 2008 and 2018. Cytogenetic abnormalities at diagnosis and pretransplantation were categorized based on the 2017 European Leukemia Net risk stratification. Genetic abnormalities such as FLT3-ITD and NPM1 were not considered in this study due to lack of genetic information in most patients. We defined cytogenetic evolution as chromosomal changes classified from lower category to higher category. Seventeen patients (8%) had cytogenetic evolution between diagnosis and pretransplantation, and they showed a significantly worse relapse rate than those who were categorized in the intermediate group based on the karyotype at diagnosis (3-year confidence interval [CI] of relapse, 57.4% versus 24.9%; P < .01). In multivariate analysis, cytogenetic evolution before allo-SCT had a significant impact on the CI of relapse (hazard ratio [HR], 3.89; CI, 1.75 to 8.67; P < .01), as well as the high score of the hematopoietic cell transplantation-specific comorbidity index (HR, 0.54; CI, 0.31 to 0.94; P = .03), but had no significant impact on overall survival or nonrelapse mortality. These results indicate that cytogenetic evolution has a significant impact after allo-SCT and should be considered during AML treatment.

遗传分析技术的最新进展有助于研究人员了解急性髓性白血病(AML)的发病机制。考虑到这一进展,AML核型仍然是提供风险适应治疗方法的最重要的预后因素之一。治疗期间核型改变时有发生,但其对预后的影响不大,特别是对同种异体干细胞移植(alloc - sct)。在这里,我们通过分析2008年至2018年期间在日本东京Toranomon医院首次接受同种异体sct的连续212例患者的结果,回顾性研究了诊断和移植前染色体变化对同种异体sct预后的影响。根据2017年欧洲白血病网风险分层对诊断和移植前的细胞遗传学异常进行分类。由于大多数患者缺乏遗传信息,本研究未考虑FLT3-ITD和NPM1等遗传异常。我们将细胞遗传进化定义为染色体从低级分类到高级分类的变化。17例(8%)患者在诊断和移植前有细胞遗传学进化,其复发率明显低于根据诊断时核型分类为中间组的患者(复发的3年置信区间[CI], 57.4%对24.9%;P & lt;. 01)。在多因素分析中,同种异体细胞移植前的细胞遗传进化对复发的CI有显著影响(风险比[HR], 3.89;CI, 1.75 ~ 8.67;P & lt;.01),且造血细胞移植特异性合并症指数得分较高(HR, 0.54;CI, 0.31 ~ 0.94;P = .03),但对总生存率和非复发死亡率没有显著影响。这些结果表明,细胞遗传学进化在同种异体细胞移植后具有显著影响,在AML治疗中应予以考虑。
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引用次数: 3
Barriers to Hematopoietic Cell Transplantation for Adults in the United States: A Systematic Review with a Focus on Age 美国成人造血细胞移植的障碍:一项以年龄为重点的系统综述
IF 4.3 Q1 Medicine Pub Date : 2020-12-01 DOI: 10.1016/j.bbmt.2020.09.013
Colin Flannelly , Bryan E-Xin Tan , Jian Liang Tan , Colin M. McHugh , Chandrika Sanapala , Tara Lagu , Jane L. Liesveld , Omar Aljitawi , Michael W. Becker , Jason H. Mendler , Heidi D. Klepin , Wendy Stock , Tanya M. Wildes , Andrew Artz , Navneet S. Majhail , Kah Poh Loh

Hematopoietic cell transplantation (HCT) is an effective treatment for many hematologic malignancies, and its utilization continues to rise. However, due to the difficult logistics and high cost of HCT, there are significant barriers to accessing the procedure; these barriers are likely greater for older patients. Although numerous factors may influence HCT access, no formal analysis has detailed the cumulative barriers that have been studied thus far. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to better categorize the barriers to access and referral to HCT, with a focus on the subgroup of older patients. We searched for articles published in English from PubMed, Embase, Cumulative Index for Nursing and Allied Health, and Cochrane Central Register of Controlled Trials between the database inception and January 31, 2020. We selected articles that met the following inclusion criteria: (1) study design: qualitative, cross-sectional, observational cohort, or mixed-method study designs; (2) outcomes: barriers related to patient and physician access to HCT; and (3) population: adults aged ≥18 years with hematologic malignancies within the United States. Abstracts without full text were excluded. QUALSYST methodology was used to determine article quality. Data on the barriers to access and referral for HCT were extracted, along with other study characteristics. We summarized the findings using descriptive statistics. We included 26 of 3859 studies screened for inclusion criteria. Twenty studies were retrospective cohorts and 4 were cross-sectional. There was 1 prospective cohort study and 1 mixed-method study. Only 1 study was rated as high quality, and 16 were rated as fair. Seventeen studies analyzed age as a potential barrier to HCT referral and access, with 16 finding older age to be a barrier. Other consistent barriers to HCT referral and access included nonwhite race (n = 16/20 studies), insurance status (n = 13/14 studies), comorbidities (n = 10/11 studies), and lower socioeconomic status (n = 7/8 studies). High-quality studies are lacking related to HCT barriers. Older age and nonwhite race were consistently linked to reduced access to HCT. To produce a more just health care system, strategies to overcome these barriers for vulnerable populations should be prioritized. Examples include patient and physician education, as well as geriatric assessment guided care models that can be readily incorporated into clinical practice.

造血细胞移植(HCT)是一种有效的治疗许多血液系统恶性肿瘤,其使用率持续上升。然而,由于HCT的后勤困难和高成本,在获得该程序方面存在重大障碍;这些障碍对老年患者来说可能更大。虽然有许多因素可能影响HCT的获取,但迄今为止还没有正式的分析详细说明所研究的累积障碍。我们根据系统评价和荟萃分析指南的首选报告项目进行了系统评价,以更好地分类获得和转诊HCT的障碍,重点关注老年患者亚组。我们检索了从数据库建立到2020年1月31日之间从PubMed、Embase、护理和联合健康累积索引和Cochrane中央对照试验注册中心发表的英文文章。我们选择符合以下纳入标准的文章:(1)研究设计:定性、横断面、观察队列或混合方法研究设计;(2)结果:与患者和医生获得HCT相关的障碍;(3)人群:美国境内年龄≥18岁的恶性血液病患者。没有全文的摘要被排除在外。采用QUALSYST方法确定文章质量。提取了关于HCT获取和转诊障碍的数据,以及其他研究特征。我们用描述性统计对研究结果进行了总结。我们纳入了3859项研究中的26项。20项研究为回顾性队列研究,4项为横断面研究。有1项前瞻性队列研究和1项混合方法研究。只有1项研究被评为高质量,16项研究被评为一般。17项研究分析了年龄作为HCT转诊和获取的潜在障碍,其中16项研究发现年龄较大是一个障碍。其他一致的HCT转诊和获取障碍包括非白人种族(n = 16/20项研究)、保险状况(n = 13/14项研究)、合并症(n = 10/11项研究)和较低的社会经济地位(n = 7/8项研究)。缺乏与HCT障碍相关的高质量研究。年龄较大和非白种人始终与较少获得HCT有关。为了建立一个更加公正的卫生保健系统,应优先考虑为弱势群体克服这些障碍的战略。例子包括病人和医生教育,以及可以很容易地纳入临床实践的老年评估指导护理模式。
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引用次数: 24
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Biology of Blood and Marrow Transplantation
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