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一家三级政府专科医院的自体干细胞移植模式,重点关注收获前CD34+水平的移植结果。

Pattern of autologous stem cell transplants at a tertiary care government hospital, with emphasis on transplant outcomes with pre-harvest CD34+ level.

作者信息

Dolai Tuphan Kanti, De Rajib, Sen Ankita, Baul Shuvra Neel, Mitra Sumit, Bhattacharya Subham, Mondal Indrani, Mukhopadhyay Kaushik, Chattopadhyay Arnab, Dutta Shyamali, Mandal Prakas Kumar

机构信息

Department of Haematology, Nil Ratan Sircar Medical College and Hospital, Kolkata, India.

Department of Pharmacology, AIIMS, Kalyani, West Bengal, India.

出版信息

Blood Cell Ther. 2022 Feb 18;5(1):16-26. doi: 10.31547/bct-2021-010. eCollection 2022 Feb 25.

DOI:10.31547/bct-2021-010
PMID:36714265
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9847276/
Abstract

PURPOSE

Autologous stem cell transplantation (ASCT) is an established therapy for many hematological diseases. This study assessed the pattern of ASCTs at a tertiary care center and associated factors, including pre-harvest CD34+ stem cell levels, leading to improved engraftment outcomes.

METHODOLOGY

A retrospective study was conducted in India, between February 2009-August 2020. Patients who underwent ASCT for different hematological malignancies (n=65) were included, and the patients' age, sex, type and stage of disease, pre- and post-harvest CD34+ counts, and time to attain platelet/neutrophil engraftment or febrile neutropenia were analyzed. The post-harvest CD34+ dose was calculated. Pre-conditioning was performed using Granulocyte Colony Stimulating Factor (GCSF)±Plerixafor. Progression-free survival (PFS) was calculated using relapse/death as the endpoint.

RESULTS

The median age of the cohort (n=65) was 49 years, with a male preponderance. Multiple myeloma was the most common malignancy (70.8% [46/65]), requiring ASCT. The median time to ASCT was 13 months. All patients had received GCSF, while Plerixafor was used in 17 patients with a pre-harvest CD34+ count of <10 cells/μL. The median pre-harvest CD34+ concentration and post-harvest CD34+ cell dose was 27.54 cells/μL (n=26) and 5.23×10 cells/kg body weight (n=65), respectively. The median time to engraftment was 11 and 12 days, for neutrophils and platelets, respectively. One patient did not engraft and was excluded from the analysis. The time required to attain neutrophil engraftment was significantly lower (=0.02) among freshly harvested stem cells (n=48) than that of cryopreserved products (n=17). Platelet engraftment associated with CD34+ pre- and post-harvest levels was not significant (=0.06). The time to attain neutropenia and subsequent febrile neutropenia was significantly lower with an adequate post-harvest CD34+ dose (=0.009). Febrile neutropenia was seen in 83.1% (54/65) patients. The median time for febrile neutropenia was 4 days post-ASCT. Pre- and post-harvest CD34+ concentrations were directly proportional to each other (<0.001). The median PFS was 112 months (n=65). Survival was better in males (median PFS: 112 months) vs. females (median PFS: 59 months) (=0.27). Eight patients relapsed, and eight patients had died.

CONCLUSION

Although unrelated to age or sex, the post-harvest CD34+ dose was inversely related to febrile neutropenia. As pre- and post-harvest CD34+ levels were directly proportional, pre-harvest CD34+ concentrations may be reliably used to assess engraftment outcomes. Rapid neutrophil engraftment was noted in fresh stem cells with PFS of 112 months, and was better among males, the exact reason being unknown. Thus, a larger number of patients should be followed up to obtain an accurate picture.

摘要

目的

自体干细胞移植(ASCT)是治疗多种血液系统疾病的既定疗法。本研究评估了一家三级医疗中心的ASCT模式及相关因素,包括收获前CD34+干细胞水平,这些因素可改善植入结果。

方法

于2009年2月至2020年8月在印度进行了一项回顾性研究。纳入了因不同血液系统恶性肿瘤接受ASCT的患者(n = 65),分析了患者的年龄、性别、疾病类型和分期、收获前后的CD34+计数以及达到血小板/中性粒细胞植入或发热性中性粒细胞减少的时间。计算了收获后CD34+剂量。预处理使用粒细胞集落刺激因子(GCSF)±普乐沙福进行。无进展生存期(PFS)以复发/死亡为终点进行计算。

结果

该队列(n = 65)的中位年龄为49岁,男性占多数。多发性骨髓瘤是最常见的需要ASCT的恶性肿瘤(70.8% [46/65])。ASCT的中位时间为13个月。所有患者均接受了GCSF,17例收获前CD34+计数<10个细胞/μL的患者使用了普乐沙福。收获前CD34+浓度中位数和收获后CD34+细胞剂量分别为27.54个细胞/μL(n = 26)和5.23×10个细胞/千克体重(n = 65)。中性粒细胞和血小板植入的中位时间分别为11天和12天。1例患者未植入,被排除在分析之外。新鲜收获的干细胞(n = 48)中达到中性粒细胞植入所需的时间显著低于冷冻保存产品(n = 17)(P = 0.02)。收获前后CD34+水平与血小板植入的相关性不显著(P = 0.06)。收获后CD34+剂量充足时,达到中性粒细胞减少及随后发热性中性粒细胞减少的时间显著缩短(P = 0.009)。83.1%(54/65)的患者出现发热性中性粒细胞减少。发热性中性粒细胞减少的中位时间为ASCT后4天。收获前后CD34+浓度呈正相关(P < 0.001)。中位PFS为112个月(n = 65)。男性的生存率更好(中位PFS:112个月),而女性为(中位PFS:59个月)(P = 0.27)。8例患者复发,8例患者死亡。

结论

尽管与年龄或性别无关,但收获后CD34+剂量与发热性中性粒细胞减少呈负相关。由于收获前后CD34+水平呈正相关,收获前CD34+浓度可可靠地用于评估植入结果。新鲜干细胞中中性粒细胞快速植入,PFS为112个月,男性情况更好,确切原因不明。因此,应随访更多患者以获得准确情况。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ac/9847276/3e7ec5271da1/2432-7026-5-1-0016-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ac/9847276/f2a5d4f5ca47/2432-7026-5-1-0016-g001a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ac/9847276/028790629640/2432-7026-5-1-0016-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ac/9847276/3e7ec5271da1/2432-7026-5-1-0016-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ac/9847276/f2a5d4f5ca47/2432-7026-5-1-0016-g001a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ac/9847276/2a9e4698f5e3/2432-7026-5-1-0016-g001b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ac/9847276/6785fe05d274/2432-7026-5-1-0016-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ac/9847276/028790629640/2432-7026-5-1-0016-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1ac/9847276/3e7ec5271da1/2432-7026-5-1-0016-g005.jpg

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Br J Haematol. 2021 May;193(3):551-555. doi: 10.1111/bjh.16793. Epub 2020 Jun 10.
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Current Use of and Trends in Hematopoietic Cell Transplantation in the United States.美国造血细胞移植的当前使用情况及趋势
Biol Blood Marrow Transplant. 2020 Aug;26(8):e177-e182. doi: 10.1016/j.bbmt.2020.04.013. Epub 2020 May 11.
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Clinical predictors of delayed engraftment in autologous hematopoietic cell transplant recipients.
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Hematol Oncol Stem Cell Ther. 2020 Mar;13(1):23-31. doi: 10.1016/j.hemonc.2019.08.003. Epub 2019 Oct 10.
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Cryopreservation of Hematopoietic Stem Cells: Emerging Assays, Cryoprotectant Agents, and Technology to Improve Outcomes.造血干细胞的冷冻保存:改善结果的新兴检测方法、冷冻保护剂和技术
Transfus Med Hemother. 2019 Jun;46(3):188-196. doi: 10.1159/000496068. Epub 2019 Feb 5.
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