Potential value of detection of minimal residual disease in colorectal cancer following radical resection

Although there has been significant advancement in the identification and management of colorectal cancer(CRC)in recent years,there is still room for improvement in the current standard treatment regimen.One area of concern is the lack of reliable tumor markers to predict treatment efficacy and guide tailored care.Due to its dynamic,effective,and non-invasive benefits over tissue biopsy,the detection of minimal or molecular residual lesions(MRD)based on circulating tumor DNA(ctDNA)is beneficial to the clinical development of drugs for patients with CRC after radical treatment,as well as for continuous monitoring of tumor recurrence and malignancy molecular gene evolution.The detection of ctDNA can currently be used to guide individual postoperative auxiliary treatment decisions(upgrade or downgrade treatment)in CRC,stratify the risk of clinical recurrence more precisely,and predict the risk of recurrence in advance of imaging examination,according to a large number of observational or prospective clinical studies.With increasing clarity comes the possibility of selecting a regimen of treatment based on postoperative ctDNA,which also improves the accuracy of clinical recurrence risk assessment for CRC.Therefore,it is anticipated that the identification of ctDNA would alter the current framework for dealing with CRC and lead to individualized,stratified precision therapy;however,additional confirmation will require subsequent high-quality,prospective,large-scale randomized controlled studies.This article will provide an overview of the definition and clinical significance of MRD,the primary indications and technological challenges for MRD detection,along with the advancement in clinical research about ctDNA detection following radical resection of the CRC.

Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI.

Prognostic relevance of minimal residual disease in colorectal cancer

Presence of occult minimal residual disease in patients with colorectal cancer(CRC)has a strong prognostic impact on survival.Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC.Analysis of circulating tumor cells(CTC)in the blood is increasingly used in clinical practice for disease monitoring of CRC patients.In this review article the role of CTC,disseminated tumor cells(DTC)in the bone marrow and micrometastases and isolated tumor cells(ITC)in the lymph nodes will be discussed,including literature published until September 2013.Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood,DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes.Minimal residual disease could be used in the future to identify patient groups at risk,who might benefit from individualized treatment options.

A comparison of flow cytometry detection of minimal residual disease and chimerism kinetics in chronic lymphocytic leukemia patients after allogeneic hematopoietic stem cell transplantation

Determination of minimal residual disease (MRD) remains crucial for the follow-up after therapy in chronic lymphocytic leukemia (CLL) patients. Chimerism was assessed by short tandem repeat (STR)-PCR and single nucleotide polymorphisms (SNP)-PCR, and MRD by a multicolor flow cytometric approach in 12 consecutive patients with CLL after they received allogeneic stem cell transplantation (SCT). Overall, 11 patients achieved MRD flow negativity [10 had full donor chimerism (FDC) and one had mixed chimerism (MC)]. Only one patient remained with MRD flow positivity and displayed MC. Fifty-six samples were concomitantly studied by both chimerism and MRD flow. A significant correlation was observed between MRD flow data and chimerism in both PB and BM by using a mixed effect linear regression (p < 0.001). Flow cytometry approach of MRD can be easily combined with chimerism during the follow-up post-allogeneic SCT. Both techniques appeared complementary for guiding post-transplant immunomodulation.

Coexisting opportunities and challenges:In which scenarios can minimal/measurable residual disease play a role in advanced non-small cell lung cancer?

Curative therapy was not previously available for patients with advanced non-small cell lung cancer(NSCLC);thus,the concept of minimal/measurable(or molecular)residual disease(MRD)was not applicable to these patients.However,advances in targeted and immunotherapy have revolutionized the treatment landscape for patients with advanced NSCLC,with emerging evidence of long-term survival and even the hope of complete remission(CR)by imaging examination.The latest research shows that patients with oligometastatic lung cancer can benefit from local treatment.After removing the lesions,the choice of follow-up therapy and monitoring of the lesions could remain uncertain.MRD plays a role in identifying early-stage NSCLC patients with high risks of recurrence and determining adjuvant therapy after radical treatment.In recent years,evidence has been accumulating regarding the use of circulating cell-free tumor DNA(ctDNA)to assess MRD in solid tumors.This study discussed the possible applications of ctDNA-based MRD monitoring in advanced NSCLC and described the current challenges and unresolved problems in the application of MRD in advanced NSCLC.

DETECTION AND ITS CLINICAL VALUE OF MINIMAL RESIDUAL DISEASES IN ACUTE PROMYELOCYTIC LEUKEMIA

Objective: To detect the minimal residual diseases (MRD) in acute promyelocytic leukemia (APL) after complete remission (CR) and to analyze its clinical value in prognosis. Methods: Reverse transcription Polymerase chain reaction (RT/PCR) was used to detect MRD of patients with APL. Results: MRD positive rate in patients with APL was 92.8% (39/42) before treatment and 56.7 (21/37) immediately after the ATRA or chemotherapy-induced CR. Furthermore, MRD positive rate was related to the relapse in APL patients and could be considered as a marker to predict the relapse of patients with APL after CR. The MRD detection could also be applied to direct the consolidation therapy to prevent relapses. Conclusion: RT-PCR is valuable to monitor MRD and can be used as a marker to predict relapses.

CLINICAL SIGNIFICANCE OF THE DETECTION OF MINIMAL RESIDUAL DISEASE IN CHILDHOOD B-ALL BY FLOW CYTOMETRY

Objective To detect the minimal residual disease in children with B-ALL and to evaluate its clinical significance by flow cytometry. Methods 58 childhood B-ALL cases were enrolled into this study and 33 MRD analyses were performed after remission induction therapy.Four-color combinations of fluorochrome labeled monoclonal antibodies against lymphocyte lineage related phenotypes were used to analyze leukemic cells with flow cytometry.The cells from normal bone marrow were used as controls.The combinations of phenotypes that reflect the antigen expression differences between leukemic and normal bone marrow cells on flow cytometry were considered to be the effective phenotype combinations in the first step screening.The effective phenotype combinations were then used to monitor MRD during the disease course after therapy began. Results 58 cases of childhood B-ALL were screened for MRD effective phenotype combinations.The effective phenotype combinations were identified in 89.7% of B-ALL cases in this study.Four-color phenotype combinations were composed of CD10/CD34/CD19 plus another effective marker such as CD38,CD58,CD66c,CD21.The senstitivity of this method was 0.01%,much higher than that of microscopic inspection.In 8 cases,their bone marrow microscopic inspection results showed no remaining leukemic cells;but with flow cytometry,the percentage of leukemic cells were 5.66%,0.36%,1.43%,0.069%,1.55%,2.7%,0.028% and 0.015%,respectively.In risk stratification,all these MRD positive cases were classified into high risk group for relapse and 1 case showed early relapse within 6 months. Conclusion The application of flow cytometry in MRD measurement can significantly improve the sensitivity of detection of remained leukemic cells in childhood B-ALL,and can provide more accurate information on disease progression as well as the efficacy of therapy,thus facilitate future treatment decisions and follow ups.

Study of Minimal Residual Disease in Adults with B-Lineage Acute Lymphoblastic Leukemia by Flowcytometry

Background: After achieving morphological remission, existence of few number of leukemic cells in the patient’s blood represents the minimal residual disease (MRD) and its monitoring helps in evaluating early treatment response and future relapse. Patients and methods: Eighty seven newly diagnosed (B-ALL) cases were enrolled in the present study in the time period from October 2013 to October 2016. A panel of 4 monoclonal antibodies (CD10FITC, CD19PE, CD34PercP and CD45APC) were defined at diagnosis and after morphological remission for tracing of minimal residual disease (MRD). Results: Eighty seven newly diagnosed B-ALL cases were included in the present study of which 73 (84%) showed positive expression to CD45 in combination with (CD10, CD19 and CD34) at diagnosis, which allow us to use this combination for further assessment of MRD after morphological remission. In our study 65% of patients had negative MRD ( Conclusion: MRD detection by flow cytometry using the combination of CD45 with CD10, CD19 & CD34 is an easy and reliable method. Patients with positive MRD are at higher risk of relapse and have inferior overall survival rates compared to those with MRD-ve. Future studies focusing on treatment intensification for the group of patients with +ve MRD aiming to improve the treatment outcome are warranted.

Liquid biopsy and blood-based minimal residual disease evaluation in multiple myeloma

Novel drug availability has increased the depth of response and revolutionised the outcomes of multiple myeloma patients.Minimal residual disease evaluation is a surrogate for progression-free survival and overall survival and has become widely used not-only in clinical trials but also in daily patient management.Bone marrow aspiration is the gold standard for response evaluation,but due to the patchy nature of myeloma,false negatives are possible.Liquid biopsy and blood-based minimal residual disease evaluation consider circulating plasma cells,mass spectrometry or circulating tumour DNA.This approach is less invasive,can provide a more comprehensive picture of the disease and could become the future of response evaluation in multiple myeloma patients.

Brentuximab Vedotin Monotherapy and Combined with Low Dose Donor Lymphocyte Infusion to Control Minimal Residual Disease and Sustain Clinical Remission in a Child with Relapsed Anaplastic Large Cell Lymphoma

Minimal residual disease (MRD) appears to have a strong negative predictive value for disease recurrence in children with anaplastic large cell lymphoma (ALCL). Brentuximab vedotin (BV) can be a therapeutic option for MRD-positive patients to achieve molecular remission and to decrease risk of subsequent relapse. We here report a 4-year-old child with ALCL progression during relapse treatment who received BV as a bridging therapy before haploidentical hematopoietic stem-cell transplantation, and as a maintenance therapy post-transplant alone or combined with simultaneous low dose donor-lymphocyte infusions. MRD monitoring showed a complete molecular response and reflected both BV efficiency and graft-versus-lymphoma effect.

The potential role of minimal/molecular residual disease in colorectal cancer: curative surgery, radiotherapy and beyond

Detection of minimal/molecular residual disease(MRD)based on ctDNA assay develops from hematological malignancies to solid tumors.Generally,there are two mainstream assays in MRD testing technology:tumor-informed and tumor-agnostic.For colorectal cancer(CRC),MRD is used not only to monitor recurrence and predict prognosis,but also to help in clinical decision making and assessment of clinical efficacy in the settings of curative surgery,radiotherapy,chemotherapy and surveillance.Accumulated clinical trials are exploring roles of MRD in early or advanced stages of CRC.Here,we give an overview of how MRD is and will be used in CRC.

AML化疗期间不同时间点流式细胞术MRD检测对预后的影响

目的:探讨AML化疗期间不同时间点流式细胞术微小残留病(MRD)检测对预后的影响。方法:回顾性分析2018年3月到2022年3月确诊并规范化疗的130例成人原发AML患者,用流式细胞术检测MRD,Kaplan-Meier曲线进行生存分析,log-rank检验进行差异性分析,Cox比例风险回归模型进行影响患者生存的单因素和多因素分析。竞争风险模型进行影响患者累计复发率(CIR)的分析,Fine-Gray进行差异性分析。结果:130例患者中,CR181例,CR226例,PR 14例,NR 9例。CR1组OS高于CR2、PR、NR组。CR2组OS高于PR组,但与NR组比较无统计学差异;PR组OS与NR组比较无统计学差异。CR1和CR2的107例患者根据流式细胞术检测的MRD分组,第一次诱导化疗后MRD~-和MRD~+组患者的4年预期RFS率分别为65.3%和27.9%,4年预期OS率分别为58.7%和41.4%,4年预计CIR率分别为34.7%和69.7%,2组比较差异均有统计学意义(χ^(2)=6.639,P=0.010;χ^(2)=6.131,P=0.013;χ^(2)=6.637,P=0.010);第二次化疗后MRD~-和MRD~+组患者的4年预期RFS率分别为50.8%和37.9%,4年预期OS率分别为49.2%和44.5%,4年预计CIR率分别为49.2%和59.5%,2组比较差异均无统计学意义(χ^(2)=1.475,P=0.225;χ^(2)=2.432,P=0.119;χ^(2)=1.416,P=0.234);巩固治疗期间MRD~-和MRD~+组患者的4年预期RFS率分别为51.9%和29.6%,4年预期OS率分别为67.5%和24.6%,4年预计CIR率分别为48.1%和70.4%,2组比较差异均有统计学意义(χ^(2)=20.982,P<0.001;χ^(2)=17.794,P<0.001;χ^(2)=19.879,P<0.001);3个时间点MRD均为阴性和任一时间点为阳性患者的4年预期RFS率分别为69.9%和33.3%,4年预期OS率分别为59.1%和44.7%,4年预计CIR率分别为30.1%和65.1%,2组比较差异均有统计学意义(χ^(2)=7.367,P=0.007;χ^(2)=6.042,P=0.014;χ^(2)=7.662,P=0.006)。单因素分析结果显示,染色体高危核型是影响患者RFS和OS的不利因素,诱导化疗2个疗程达CR、第一次诱导化疗后MRD~-和第二次化疗MRD~-是患者RFS和OS的保护因素;巩固治疗期间MRD~-和3个时间点MRD~-是患者RFS、OS和CIR的保护因素。多因素分析结果显示,诱导化疗2个疗程达CR是患者RFS和CIR的保护因素,巩固治疗期间MRD~-是RFS、OS和CIR的保护因素。结论:成人AML患者早期获得CR和MRD~-,特别是巩固治疗期间的MRD~-是预后良好的标志,流式细胞术是AML患者MRD检测最常用的方法。

极限稀释定量PCR法动态监测儿童急性淋巴细胞性白血病MRD

为探讨一种简便易行检测儿童急性淋巴细胞性白血病 (AL L)微小残留白血病 (MRD)的方法 ,应用 Chelex10 0为介质抽提 4 1例 AL L 患儿不同病期未染色骨髓涂片 DNA,以 TCR Vδ2 Dδ3基因重排为标志 ,采用极限稀释定量PCR法扩增 ,动态监测 MRD的消长与临床病情变化的关系。结果发现 :2 4例患儿在初诊时检出 TCR Vδ2 Dδ3基因重排(5 9% ) ,灵敏度均为 4个拷贝。经诱导缓解后 ,12例 TCR Vδ2 Dδ3基因重排仍为阳性 ,MRD值为 2× 10 - 6 ～ 1× 10 - 3,其中 7例 MRD值于 3～ 6个月内迅速下降转阴 ,骨髓检测未见复发 ,另 5例 MRD持续阳性或 MRD持续高值 ,早期复发。骨髓检测复发患儿缓解期时 MRD平均值为 1.9× 10 — 3明显高于同期骨髓检测未复发患儿的 3× 10 - 6 (P<0 .0 1)。余 12例诱导缓解后 TCR Vδ2 Dδ3基因重排转阴 ,MRD值均 <1× 10 - 6 ,其中 3例 MRD由阴性转阳后加强化疗力度 ,未复发。结果提示 :以 Chelex 10 0为介质抽提 DNA进行 PCR扩增 ,操作简便 ,敏感度高 ;动态监测 MRD的消长对指导临床治疗 。

初发急性髓系白血病诱导化疗后外周血MRD早期检测与临床疗效的关系

本研究旨在检测初发急性髓系白血病(AML)患者诱导化疗第8天外周血残存的白血病细胞数量,探索其与诱导缓解及生存时间之间的关系。收集华西医院血液科2009年9月至2010年6月的29例初发AML患者的临床和实验室资料,其中男13例,女16例,中位年龄41(16-75)岁。根据初诊时白血病相关免疫表型特征(LAIP),采用流式细胞术检测患者诱导化疗第8天外周血微小残留病(MRD)细胞数量;应用Kaplan-Meier法计算生存曲线,对数秩检验进行单因素生存分析,观察患者外周血化疗第8天MRD水平与治疗后完全缓解率(CR)及总体生存率之间的关系。结果表明,29例AML患者经第1疗程化疗后,7例外周血MRD水平低于0.01%(阴性组),其余22例外周血MRD水平高于0.01%(0.08%-55%,阳性组);两组患者在性别、年龄、WBC、乳酸脱氢酶水平、骨髓原始细胞比例等均无统计学差异。7例MRD阴性组中6例达CR(86%),22例MRD阳性组中6例达CR(27%),CR率差异有统计学意义(P<0.05)。随访时间1-28个月(中位时间15个月),MRD阴性组患者中位生存期为19个月,MRD阳性组患者中位生存期为9个月(P<0.05),MRD阴性组1年生存率(100%)明显高于阳性组(39.4%,P<0.01)。结论:采用流式细胞术检测AML患者诱导化疗后第8天外周血MRD水平能较好的预测患者的CR率与长期生存率,MRD阴性患者有更高的CR率和更长的生存期。

CD7、CD56、CD19在AML预后及MRD监测中的意义

目的探讨急性髓系白血病伴淋系抗原(Ly+-AML)表达者在预后及白血病微小残留病(MRD)监测中的临床意义。方法利用流式细胞术(FCM)对86例AML进行免疫分型,并以CD7、CD56、CD19为标志进行MRD检测。结果交叉表达现象在M5中出现频率最高,其次为M2;CD7表达在Ly+-AML中最常见;首次化疗形态学完全缓解(CR)率Ly+-AML病例低于Ly--AML病例;2年死亡率Ly+-AML病例高于Ly--AML病例;在MRD阳性检出率方面,CD7+AML组与Ly--AML组之间差异有统计学意义(P1<0.05),CD56+AML组与Ly--AML组之间差异有统计学意义(P2<0.05),CD19+AML组与Ly--AML组之间差异无统计学意义(P3>0.05)。讨论 Ly+-AML与Ly--AML有不同的临床特点,CD7+AML和CD56+AML预后差;CD7、CD56可以作为MRD监测的重要指标。

DC-CIK细胞用于治疗急性髓系白血病MRD的研究

目的:探讨DC-CIK细胞治疗急性髓系白血病微小残留病灶的疗效。方法:对11例经化疗后MRD阳性的急性髓系白血病患者进行DC-CIK过继免疫治疗,并用FCM监测MRD变化。结果:经FCM检测,11例患者中7例MRD转阴,并处于持续完全缓解状态,其余4例(M21例,M42例,M51例)均复发。结论:DC-CIK过继免疫治疗具有清除急性髓系白血病MRD的作用。

中危初诊中青年AML患者预后的影响因素及巩固治疗前MRD预测价值研究

目的:探讨中危初诊中青年急性髓系白血病(AML)患者预后的影响因素及巩固治疗前微小残留病变(MRD)预测价值。方法:回顾性选取本院2010年1月-2018年12月收治中危初诊中青年AML共262例,所有患者均在诱导化疗后达形态学无白血病状态(MLFS),对患者的总体和亚组临床数据进行分析。采用Cox回归模型评价中危初诊中青年AML患者的预后独立影响因素。结果:<40岁的患者中,巩固治疗接受PR-CT和allo-HSCT方案5年累积无白血病生存(LFS)率分别为40.92%、63.51%(P=0.01);而≥40岁的患者则分别为23.61%、49.14%(P=0.00);诱导化疗早期缓解和晚期缓解5年累积LFS率分别为63.51%、41.33%(P=0.01);接受PR-CT和allo-HSCT方案治疗5年累积总生存(OS)率分别为23.65%、69.32%(P=0.00),5年累积LFS率分别为26.44%、52.30%(P=0.01)。接受PR-CT巩固治疗的患者中,MRD阴性和阳性分别为74和60例;MRD阴性亚组5年累积复发率显著低于MRD阳性亚组(P<0.05);接受PR-CT患者中,MRD阴性亚组5年LFS率和OS率均显著高于MRD阳性亚组(P<0.05)。接受allo-HSCT巩固治疗的患者中,MRD阴性和阳性分别为66和62例;MRD阴性亚组5年累积复发率显著低于MRD阳性亚组(P<0.05);allo-HSCT患者中,MRD阴性亚组5年LFS率和OS率均显著高于MRD阳性亚组(P<0.05)。单因素分析结果显示,年龄、染色体核型、达MLFS后MRD状态及巩固治疗方案均与患者预后有关(P<0.05)。多因素分析结果显示,年龄、达MLFS后MRD状态及巩固治疗方案是患者累积OS率的独立影响因素(P<0.05);染色体核型是患者累积LFS率的独立影响因素(P<0.05);达MLFS后MRD状态和巩固治疗方案是影响患者累积复发率的独立影响因素(P<0.05)。结论:中危初诊中青年AML患者总生存与年龄、达MLFS后MRD状态及巩固治疗方案独立相关,而染色体核型则与患者累积LFS独立相关;对于中危中青年AML患者诱导化疗达MLFS后推荐接受allo-HSCT进行巩固治疗,尤其适用于<40岁且巩固治疗前MRD阳性人群。

流式细胞仪与显微镜联合检测MRD的临床价值

目的了解流式细胞仪与显微镜联合检测微小残留白血病细胞(MRD)的临床价值。方法采集已确诊的白血病患者65例经化疗完全缓解(CR)后的骨髓,同时用四色多参数流式细胞仪和奥林巴斯显微镜做MRD检测共233次,检测急性白血病患者完全缓解后治疗过程中不同时间点的MRD。结果 65例急性白血病患者诱导治疗缓解达CR后的233次MRD检测中,流式细胞仪MRD检测阳性率为55.4%(129/233例);显微镜FAB形态学方法检测阳性率为35.63%(83/233例)。流式细胞仪MRD监测的阳性率明显高于显微镜FAB形态学检测,两种方法结果比较,差异有统计学意义(P<0.01);233次MRD检测中59次显微镜形态学检测阴性而流式细胞仪检测阳性,13次显微镜检测阳性而流式细胞仪检测阴性。结论用四色多参数流式细胞仪能快速有效地对急性白血病患者进行MRD检测;用流式细胞仪与显微镜联合检测MRD,可避免因白血病细胞在治疗过程中某些标志丢失或改变而造成MRD假阴性,进一步提高MRD阳性检出率,对于提高急性白血病患者的生存率及生存质量和疗效评估及预后监测都具有重要意义。

MRD监测下88例儿童急性B淋巴细胞白血病长期疗效的分析

目的对88例儿童急性B淋巴细胞白血病（B—ALL）治疗的长期随访结果进行分析，探讨微小残留病（MRD）监测下儿童B—ALL的无事件生存率（EFS）。方法回顾性分析2005年1月．2008年5月接受儿童ALL诊疗建议（第三次修订草案）治疗的88例B．ALL患儿，应用流式细胞术（FCM）检测MRD，采用Kaplan—Meier方法评估患儿EFS，各临床危险度分组间患儿EFS差异用Logrank检验。结果88例患儿骨髓完全缓解（CR）率为97．7％，2年、3年、4年、5年EFS率分别为87．5％、86．4％、81．8％、77．2％，标危、中危、高危5年EFS率分别为86．2％、84．6％、63．1％。5例死亡，9例复发（10．5％），复发中位时间为23（3—59）个月。结论采用儿童ALL诊疗建议（第三次修订草案）治疗CR率较高，在MRD监测下指导治疗，总体上B—ALL患儿的5年EFS提高。

扶正透毒祛毒复方对髓系MRD-L患者CD34^+细胞源DC诱导过程中IL-2、sIL-2R的影响

【目的】研究扶正透毒祛毒复方(加味青蒿鳖甲汤)中药含药血清对髓系微小残留白血病(minimal residual disease in leukemia,MRD-L)患者CD34+细胞源树突状细胞(DC)诱导培养的不同阶段血清中白细胞介素-2(IL-2)、可溶性白细胞介素-2受体(sIL-2R)的含量变化,探讨扶正透毒祛毒复方影响MRD-L患者CD34+细胞源DC诱导及生物学效应的机制。【方法】将急性髓系白血病缓解期(AML-CR)患者骨髓经Ficoll密度梯度离心获得骨髓单个核细胞(BMNC)后,用免疫磁珠阳性选择法提取CD34+细胞,培养扩增后用不同浓度中药含药血清与细胞因子进行体外培养诱导DC,培养过程中观察细胞的形态,流式细胞仪检测DC表面CD83、CD80、CD86、CD1a、人白细胞DR抗原(HLA-DR)的表达。在培养的第0天、第6天和第9天采用酶联免疫吸附(ELISA)法分别检测、比较各组血清中IL-2、sIL-2R的含量。【结果】(1)各中药含药血清联合细胞因子组能促进CD34+细胞分化为形态特征典型的DC,并高表达CD83、CD80、CD86、HLA-DR等DC的表面标志,与胎牛血清及空白兔血清组比较差异有统计学意义(P<0.01),中药中剂量及低剂量含药血清组能促进CD1a的表达提高,与中药高剂量组、细胞因子组比较差异有统计学意义(P<0.01)。(2)IL-2含量:含药血清制成后(第0天),各中药含药血清组均高于空白兔血清组;各中药含药血清联合细胞因子组第9天、第6天均高于第0天,中药中剂量联合细胞因子组第9天显著高于第6天(P<0.01),中药高剂量联合细胞因子组第9天高于第6天(P<0.05);在同一时间内,各中药含药血清联合细胞因子组均高于空白兔血清组。(3)sIL-2R含量:含药血清制成后(第0天),各中药含药血清组均低于空白兔血清组;各中药含药血清联合细胞因子组第9天均显著低于第0天、第6天(P<0.01),中药高剂量联合细胞因子组第6天低于第0天(P<0.05),其余各组第6天与第0天比较差异无统计学意义(P>0.05);在同一时间内,各中药含药血清联合细胞因子组均低于空白兔血清组(P<0.05或P<0.01)。【结论】扶正透毒祛毒复方能增加血清IL-2的含量和降低sIL-2R的水平,随着DC的不断成熟,其含量变化更加明显,可能对CD34+细胞向DC转化发挥了积极作用。