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Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34+ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation.在减低预处理强度的动员外周血异基因造血细胞移植中,输注的总有核细胞剂量比CD34+细胞数量更能预测移植结果。
Haematologica. 2016 Apr;101(4):499-505. doi: 10.3324/haematol.2015.134841. Epub 2016 Jan 14.
2
Higher doses of CD34+ progenitors are associated with improved overall survival without increasing GVHD in reduced intensity conditioning allogeneic transplant recipients with clinically advanced disease.在患有临床晚期疾病的减低强度预处理异基因移植受者中,更高剂量的CD34+祖细胞与总体生存率提高相关,且不会增加移植物抗宿主病(GVHD)。
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Alloreactivity as therapeutic principle in the treatment of hematologic malignancies. Studies of clinical and immunologic aspects of allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.异基因反应性作为血液系统恶性肿瘤治疗的治疗原则。非清髓性预处理的异基因造血细胞移植的临床和免疫学方面的研究。
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High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation.高剂量移植的CD34+细胞与快速的T细胞植入及降低移植物排斥风险相关,但在非清髓性预处理和无关造血细胞移植后,并不会增加移植物抗宿主病的发生。
Leukemia. 2005 May;19(5):822-8. doi: 10.1038/sj.leu.2403718.
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Flow Cytometric Characterization of Hematopoietic Stem and Progenitor Cell Subpopulations in Autologous Peripheral Blood Stem Cell Preparations after Cryopreservation.冷冻保存后自体外周血干细胞制品中造血干细胞和祖细胞亚群的流式细胞术特征分析
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4
Are haematopoietic stem cell transplants stem cell transplants, is there a threshold dose of CD34-positive cells and how many are needed for rapid posttransplant granulocyte recovery?造血干细胞移植属于干细胞移植吗?CD34阳性细胞是否存在一个阈值剂量,以及移植后粒细胞快速恢复需要多少该细胞?
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Higher graft cell dose does not influence development of acute or chronic GVHD in haploidentical transplantation using PTCy.在使用PTCy的单倍体移植中,较高的移植物细胞剂量不会影响急性或慢性移植物抗宿主病的发生。
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The efficiency of human umbilical cord mesenchymal stem cells as a salvage treatment for steroid-refractory acute graft-versus-host disease.人脐带间充质干细胞作为挽救治疗类固醇耐药性急性移植物抗宿主病的疗效。
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本文引用的文献

1
High Graft CD8 Cell Dose Predicts Improved Survival and Enables Better Donor Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity Conditioning.高移植CD8细胞剂量可预测异基因造血干细胞移植在减低强度预处理中的生存改善并有助于更好地选择供者。
J Clin Oncol. 2015 Jul 20;33(21):2392-8. doi: 10.1200/JCO.2014.60.1203. Epub 2015 Jun 8.
2
Effect of Total Nucleated and CD34(+) Cell Dose on Outcome after Allogeneic Hematopoietic Stem Cell Transplantation.有核细胞总数和CD34(+)细胞剂量对异基因造血干细胞移植后结局的影响。
Biol Blood Marrow Transplant. 2015 May;21(5):889-93. doi: 10.1016/j.bbmt.2015.01.025. Epub 2015 Feb 4.
3
Absolute lymphocyte count recovery after allogeneic hematopoietic stem cell transplantation predicts clinical outcome.异基因造血干细胞移植后绝对淋巴细胞计数的恢复可预测临床结局。
Biol Blood Marrow Transplant. 2015 May;21(5):873-80. doi: 10.1016/j.bbmt.2015.01.019. Epub 2015 Jan 23.
4
Donor chimerism early after reduced-intensity conditioning hematopoietic stem cell transplantation predicts relapse and survival.减低强度预处理造血干细胞移植后早期供体嵌合现象可预测复发和生存。
Biol Blood Marrow Transplant. 2014 Oct;20(10):1516-21. doi: 10.1016/j.bbmt.2014.05.025. Epub 2014 Jun 4.
5
Low CD34 dose is associated with poor survival after reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndrome.低CD34剂量与急性髓系白血病和骨髓增生异常综合征减低强度预处理异基因移植后的不良生存相关。
Biol Blood Marrow Transplant. 2014 Sep;20(9):1418-25. doi: 10.1016/j.bbmt.2014.05.021. Epub 2014 Jun 2.
6
Higher doses of CD34+ progenitors are associated with improved overall survival without increasing GVHD in reduced intensity conditioning allogeneic transplant recipients with clinically advanced disease.在患有临床晚期疾病的减低强度预处理异基因移植受者中,更高剂量的CD34+祖细胞与总体生存率提高相关,且不会增加移植物抗宿主病(GVHD)。
J Clin Apher. 2013 Oct;28(5):349-55. doi: 10.1002/jca.21278. Epub 2013 May 16.
7
A disease risk index for patients undergoing allogeneic stem cell transplantation.异体干细胞移植患者的疾病风险指数。
Blood. 2012 Jul 26;120(4):905-13. doi: 10.1182/blood-2012-03-418202. Epub 2012 Jun 18.
8
Higher incidence of relapse in patients with acute myelocytic leukemia infused with higher doses of CD34+ cells from leukapheresis products autografted during the first remission.在第一次缓解期时,自体外周血造血干细胞移植中输注更高剂量 CD34+细胞的急性髓细胞性白血病患者,其复发率更高。
Blood. 2010 Oct 28;116(17):3157-62. doi: 10.1182/blood-2009-11-252197. Epub 2010 May 17.
9
The number of infused CD34+ cells does not influence the incidence of GVHD or the outcome of allogeneic PBSC transplantation, using reduced-intensity conditioning and antithymocyte globulin.采用减低强度预处理方案和抗胸腺细胞球蛋白的情况下,输注的 CD34+ 细胞数量并不影响移植物抗宿主病的发生率或异基因 PBSC 移植的结局。
Bone Marrow Transplant. 2010 Jul;45(7):1189-96. doi: 10.1038/bmt.2009.331. Epub 2009 Nov 30.
10
The effect of the composition of unrelated donor bone marrow and peripheral blood progenitor cell grafts on transplantation outcomes.无关供者骨髓和外周血造血祖细胞移植对移植结局的影响。
Biol Blood Marrow Transplant. 2010 Feb;16(2):253-62. doi: 10.1016/j.bbmt.2009.10.004. Epub 2009 Oct 12.

在减低预处理强度的动员外周血异基因造血细胞移植中,输注的总有核细胞剂量比CD34+细胞数量更能预测移植结果。

Infused total nucleated cell dose is a better predictor of transplant outcomes than CD34+ cell number in reduced-intensity mobilized peripheral blood allogeneic hematopoietic cell transplantation.

作者信息

Martin Paul S, Li Shuli, Nikiforow Sarah, Alyea Edwin P, Antin Joseph H, Armand Philippe, Cutler Corey S, Ho Vincent T, Kekre Natasha, Koreth John, Luckey C John, Ritz Jerome, Soiffer Robert J

机构信息

Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle, WA, USA

Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.

出版信息

Haematologica. 2016 Apr;101(4):499-505. doi: 10.3324/haematol.2015.134841. Epub 2016 Jan 14.

DOI:10.3324/haematol.2015.134841
PMID:26768686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5004400/
Abstract

Mobilized peripheral blood is the most common graft source for allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning. In assessing the effect of donor cell dose and graft composition on major transplant outcomes in the reduced-intensity setting, prior studies focused primarily on CD34(+)cell dose and reported conflicting results, especially in relation to survival end-points. While the impact of total nucleated cell dose has been less frequently evaluated, available studies suggest higher total nucleated cell dose is associated with improved survival outcomes in the reduced-intensity setting. In order to further explore the relationship between CD34(+)cell dose and total nucleated cell dose on reduced-intensity transplant outcomes, we analyzed the effect of donor graft dose and composition on outcomes of 705 patients with hematologic malignancies who underwent reduced-intensity peripheral blood stem cell transplantation at the Dana Farber Cancer Institute from 2000 to 2010. By multivariable analysis we found that higher total nucleated cell dose (top quartile; ≥10.8 × 10(10)cells) was associated with improved overall survival [HR 0.69 (0.54-0.88),P=0.0028] and progression-free survival [HR 0.68 (0.54-0.85),P=0.0006]. Higher total nucleated cell dose was independently associated with decreased relapse [HR 0.66 (0.51-0.85),P=0.0012] and increased incidence of chronic graft-versus-host disease [HR 1.4 (1.12-1.77),P=0.0032]. In contrast, higher doses of CD34(+)cells (top quartile; ≥10.9 × 10(6)/kg) had no significant effect on graft-versus-host disease or survival outcomes. These data suggest total nucleated cell dose is a more relevant prognostic variable for reduced-intensity transplant outcomes than the more commonly studied CD34(+)cell dose.

摘要

动员外周血是减低预处理强度后异基因造血干细胞移植最常见的移植物来源。在评估供体细胞剂量和移植物组成对减低预处理强度情况下主要移植结局的影响时,既往研究主要聚焦于CD34(+)细胞剂量,且报道的结果相互矛盾,尤其是在生存终点方面。虽然对有核细胞总剂量的影响评估较少,但现有研究表明,在减低预处理强度情况下,较高的有核细胞总剂量与改善的生存结局相关。为了进一步探讨CD34(+)细胞剂量和有核细胞总剂量与减低预处理强度移植结局之间的关系,我们分析了2000年至2010年在达纳法伯癌症研究所接受减低预处理强度外周血干细胞移植的705例血液系统恶性肿瘤患者的供体移植物剂量和组成对结局的影响。通过多变量分析,我们发现较高的有核细胞总剂量(最高四分位数;≥10.8×10(10)个细胞)与改善的总生存[风险比0.69(0.54 - 0.88),P = 0.0028]和无进展生存[风险比0.68(0.54 - 0.85),P = 0.0006]相关。较高的有核细胞总剂量与复发减少[风险比0.66(0.51 - 0.85),P = 0.0012]和慢性移植物抗宿主病发生率增加[风险比1.4(1.12 - 1.77),P = 0.0032]独立相关。相比之下,较高剂量的CD34(+)细胞(最高四分位数;≥10.9×10(6)/kg)对移植物抗宿主病或生存结局无显著影响。这些数据表明,对于减低预处理强度的移植结局,有核细胞总剂量是比更常研究的CD34(+)细胞剂量更相关的预后变量。