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 sur...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.展开更多
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 ...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.展开更多
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 nucleo...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.展开更多
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....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.展开更多
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 ...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.展开更多
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 ch...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.展开更多
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 treatme...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.展开更多
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 w...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.展开更多
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...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.展开更多
目的:探讨免疫球蛋白重链(IgH)基因重排在多发性骨髓瘤(MM)自体造血干细胞移植(auto-HSCT)后微小残留病监测中的价值。方法:收集2018年-2022年于武汉市第一医院血液内科接受auto-HSCT的26例MM患者的临床资料,通过多重PCR联合毛细管电泳...目的:探讨免疫球蛋白重链(IgH)基因重排在多发性骨髓瘤(MM)自体造血干细胞移植(auto-HSCT)后微小残留病监测中的价值。方法:收集2018年-2022年于武汉市第一医院血液内科接受auto-HSCT的26例MM患者的临床资料,通过多重PCR联合毛细管电泳片段分析法检测IgH重排来评价微小残留病(MRD),对疾病的转归进行相关统计学分析。结果:全部26例MM患者中,男性18例,女性8例,中位年龄59(41-70)岁,移植后中位随访时间33(7-52)个月。与骨髓IgH重排阴性组(17例)比较,移植前骨髓IgH重排阳性(9例)患者移植后3个月达到CR和sCR疗效的比例更低(1/9 vs 14/17),移植后缓解持续的时间(DOR)更短(10.78±4.35 vs 15.88±5.22个月),两组DOR差异有统计学意义(P<0.05);与外周血干细胞采集物IgH重排阴性组(21例)比较,外周血干细胞采集物IgH重排阳性(5例)患者移植后3个月达到CR和sCR的比例更低(0/5 vs 15/21),移植后缓解持续的时间(DOR)更短(9.60±4.83 vs 15.19±5.11个月),两组DOR差异有统计学意义(P<0.05)。在随访期内,移植前骨髓IgH重排阳性的患者有5例(5/9)死亡,IgH重排阴性患者均存活;外周血干细胞采集物IgH重排阳性患者有4例(4/5)死亡,IgH重排阴性患者有1例死亡(1/21)。无论是骨髓还是外周血干细胞采集物标本,IgH重排阳性患者移植后生存时间较IgH重排阴性患者更短(P<0.05)。Logistic回归分析结果显示,性别、疾病分期、初诊时骨髓涂片浆细胞比例、干细胞动员方案、移植前疗效评价(≥CR和<CR)、CD34+细胞计数对移植前骨髓及干细胞采集物IgH重排均无影响(P>0.05)。结论:通过检测接受auto-HSCT的MM患者IgH重排,可以进一步评价MRD的深度,对疾病的疗效及预后判断有一定的指导意义。展开更多
1文献来源Liu SY,Dong S,Yang XN,et al.Neoadjuvant nivolumab with or without platinum⁃doublet chemotherapy based on PD⁃L1 expression in resectable NSCLC(CTONG1804):a multicenter open⁃label phaseⅡstudy[J].Signal Transdu...1文献来源Liu SY,Dong S,Yang XN,et al.Neoadjuvant nivolumab with or without platinum⁃doublet chemotherapy based on PD⁃L1 expression in resectable NSCLC(CTONG1804):a multicenter open⁃label phaseⅡstudy[J].Signal Transduct Target Ther,2023,8(1):442.2证据水平2a。展开更多
【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(s...【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。展开更多
文摘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.
文摘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.
文摘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.
基金supported by Jilin Scientific and Technological Development Program(CN)(No.20190303146SF)。
文摘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.
文摘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.
基金This work was supported by the NaturalScience Foundation of Shandong Province (No. 2000.11) and a grant from the Science & Technology Committee of Shandong Province (No. 951228104).
文摘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.
文摘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.
文摘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.
文摘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.
文摘目的:探讨免疫球蛋白重链(IgH)基因重排在多发性骨髓瘤(MM)自体造血干细胞移植(auto-HSCT)后微小残留病监测中的价值。方法:收集2018年-2022年于武汉市第一医院血液内科接受auto-HSCT的26例MM患者的临床资料,通过多重PCR联合毛细管电泳片段分析法检测IgH重排来评价微小残留病(MRD),对疾病的转归进行相关统计学分析。结果:全部26例MM患者中,男性18例,女性8例,中位年龄59(41-70)岁,移植后中位随访时间33(7-52)个月。与骨髓IgH重排阴性组(17例)比较,移植前骨髓IgH重排阳性(9例)患者移植后3个月达到CR和sCR疗效的比例更低(1/9 vs 14/17),移植后缓解持续的时间(DOR)更短(10.78±4.35 vs 15.88±5.22个月),两组DOR差异有统计学意义(P<0.05);与外周血干细胞采集物IgH重排阴性组(21例)比较,外周血干细胞采集物IgH重排阳性(5例)患者移植后3个月达到CR和sCR的比例更低(0/5 vs 15/21),移植后缓解持续的时间(DOR)更短(9.60±4.83 vs 15.19±5.11个月),两组DOR差异有统计学意义(P<0.05)。在随访期内,移植前骨髓IgH重排阳性的患者有5例(5/9)死亡,IgH重排阴性患者均存活;外周血干细胞采集物IgH重排阳性患者有4例(4/5)死亡,IgH重排阴性患者有1例死亡(1/21)。无论是骨髓还是外周血干细胞采集物标本,IgH重排阳性患者移植后生存时间较IgH重排阴性患者更短(P<0.05)。Logistic回归分析结果显示,性别、疾病分期、初诊时骨髓涂片浆细胞比例、干细胞动员方案、移植前疗效评价(≥CR和<CR)、CD34+细胞计数对移植前骨髓及干细胞采集物IgH重排均无影响(P>0.05)。结论:通过检测接受auto-HSCT的MM患者IgH重排,可以进一步评价MRD的深度,对疾病的疗效及预后判断有一定的指导意义。
文摘1文献来源Liu SY,Dong S,Yang XN,et al.Neoadjuvant nivolumab with or without platinum⁃doublet chemotherapy based on PD⁃L1 expression in resectable NSCLC(CTONG1804):a multicenter open⁃label phaseⅡstudy[J].Signal Transduct Target Ther,2023,8(1):442.2证据水平2a。
文摘【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。