恶性血液病患者异基因造血干细胞移植后巨细胞病毒感染的监测及危险因素分析

 目的　探讨应用流式细胞术（FCM）检测急性白血病（AL）患者骨髓微小残留病（MRD）对预测复发及指导治疗的临床意义。方法　选择2005年7月至2008年6月于该院住院经MIC分型确诊的初治获完全缓解（CR）的43例AL患者,应用FCM和单克隆抗体直接荧光标记法检测骨髓MRD,并动态随访。结果　对初次受检MRD阳性患者动态观察骨髓形态学,平均1～3个月复查骨髓1次,所有复发患者均在MRD阳性后4～6个月出现形态学复发。MRD随访结果显示：43例AL患者CR时MRD阴性26例,6例复发,持续阴性20例。CR时MRD阳性17例,10例复发（58.82 %）。4例经加强化疗后MRD转阴达1年以上。43例患者CR时按MRD值水平分为三组,并观察1年复发率。＜1×10-4组和5×10-3～1×10-4组1年复发率差异无统计学意义（P＝0.37）,5×10-3～1×10-4组和＞5×10-3组1年复发率差异有统计学意义（P＝0.02）。结论　应用FCM动态检测MRD对及时预测复发、指导治疗有重要的临床意义。     

抗CD20单克隆抗体联合自体外周血干细胞移植治疗非霍奇金淋巴瘤的临床研究

 目的　探讨抗CD20单克隆抗体（利妥昔单抗,商品名：美罗华）联合自体外周血干细胞移植（APBSCT）治疗B细胞非霍奇金淋巴瘤（NHL）的疗效。方法　21例CD20阳性的NHL患者,经过前期治疗,5例达完全缓解（CR）,难治性病例为16例,包括11例部分缓解（PR）和5例疾病进展（PD）。在自体造血干细胞动员的第1、8天及预处理的-1、＋7天每天应用利妥昔单抗375 mg／m2。结果　移植前疾病达到CR的5例患者,无一例复发;移植前处于PR的11例患者,仅1例在移植后6个月疾病复发,其余均无病生存;移植前处于PD的5例患者,2例无病生存。21例患者中位随访24（1～68）个月,复发、死亡4例（19 %）,其余17例均无病生存,2年无病生存（EFS）和总生存（OS）率均为81.0 %。未观察到利妥昔单抗对采集所得干细胞的质量和数量以及移植后造血恢复有不良影响。结论　APBSCT联合利妥昔单抗做体内净化治疗B细胞NHL疗效与移植前状态有关,作为巩固治疗,能使移植前达CR的患者获得长期生存,提高治愈率;作为强化治疗,可提高缓解率,延长PR患者的EFS及OS。利妥昔单抗的加入不影响造血干细胞采集和移植后造血重建。     

自体造血干细胞移植相关肝损伤的临床研究

目的探讨自体造血干细胞移植相关肝损伤的临床特点。方法回顾性分析109例接受自体造血干细胞移植的淋巴瘤患者的临床资料。结果109例淋巴瘤患者接受预处理方案化疗后,肝脏生化学的异常改变主要是氨基转移酶、总胆红素的升高,其中30.3%出现丙氨酸氨基转移酶升高,14.7%出现天门冬氨酸氨基转移酶升高,11.0%出现总胆红素升高,Ⅲ～Ⅳ度肝损伤的发生率仅为1.8%。与CBV方案比较,BEAM方案更可能导致总蛋白降低、白蛋白/球蛋白比值异常、总胆红素和间接胆红素升高。10例HBsAg阳性的淋巴瘤患者给予拉米夫定预防治疗,均未发生乙型肝炎病毒再激活。结论自体造血干细胞移植治疗淋巴瘤相关重度肝损伤的发生率低,合并乙型肝炎病毒感染者给予拉米夫定预防治疗可以有效防止乙型肝炎病毒再激活。     

硼替佐米联合自体造血干细胞移植治疗多发性骨髓瘤的临床分析

目的探讨硼替佐米联合自体造血干细胞移植治疗多发性骨髓瘤的疗效和安全性。方法对1例轻链型多发性骨髓瘤患者,采用VTD方案（硼替佐米1.3 mg/m2,d 1、4、8、11;沙利度胺200 mg,d 1～14;地塞米松10 mg,d 1～4、d 9～12）化疗3个周期获得完全缓解后再行自体造血干细胞移植,监测M蛋白、肝肾功能、骨髓像、血象等指标,移植后再行白介素-2的免疫治疗。结果自体造血干细胞移植后患者造血重建顺利,相关并发症控制较好,随访至今一直无病生存。结论硼替佐米联合自体造血干细胞移植治疗多发性骨髓瘤是安全有效的。     

Non-bacterial infections in Asian patients treated with alemtuzumab: a retrospective study of the Asian Lymphoma Study Group

This retrospective study concerns non-bacterial infections in Asian patients receiving alemtuzumab. The clinical data of 182 patients treated with alemtuzumab alone or alemtuzumab-containing chemotherapy between the years 2003 and 2009 was collected from six Asian countries. Alemtuzumab was used in the setting of frontline (n =48) or salvage (n =90) treatment, and as a part of the conditioning regimen for allogeneic stem cell transplant (n =44). Reactivation of cytomegalovirus (66/182) and varicella zoster virus (25/182), and fungal infection (31/182) including invasive pulmonary aspergillosis, were the most common infectious complications in this retrospective analysis. Thus, we recommend routine prophylaxis with valganciclovir and itraconazole, especially when alemtuzumab is used in the conditioning regimen for allogeneic stem cell transplant. Pneumocystis jirovecii pneumonia (PJP) was found in four patients (3%, 4/122) receiving alemtuzumab as conditioning for stem cell transplant or salvage treatment. Three cases of hepatitis B virus reactivation were found in antigen-negative patients, and 16 cases of tuberculosis were observed. Infection is the major complication of alemtuzumab therapy, and these infectious complications are potentially severe and life-threatening. Based on our retrospective analysis, we have constructed a guideline for antimicrobial prophylaxis in Asian patients receiving alemtuzumab therapy.     

异基因造血干细胞移植治疗首例自体移植复发霍奇金淋巴瘤的临床分析

目的探讨霍奇金淋巴瘤自体移植复发后行异基因造血干细胞2次移植的可能性和安全性。方法对1例10年前行自体造血干细胞移植复发的霍奇金淋巴瘤患者,行异基因造血干细胞移植,供者为患者母亲,采用外周血干细胞移植,预处理方案采用氟达拉滨+马法兰+兔抗人淋巴细胞免疫球蛋白,预防移植物抗宿主病采用环孢素A、霉酚酸酯、甲氨蝶呤,输注单个核细胞数14.03×108/kg,CD34+细胞6.57×106/kg。结果 2次移植后移植物成功植入,形成完全供者来源造血,移植后第20天骨髓初步植活,造血功能恢复后患者出现皮肤植物抗宿主病,FISH嵌合状态供者细胞植入率为100%,随访至今一直长期无病生存。结论异基因造血干细胞移植,可有效治疗自体移植复发的霍奇金淋巴瘤,是安全有效的挽救治疗措施。     

Fludarabine containing-regimens may adversely affect peripheral blood stem cell collection in low-grade non Hodgkin lymphoma patients

Fludarabine (FLUDA) based chemotherapy has shown promise in both initial and salvage treatment of low-grade non Hodgkin's lymphomas (LG-NHL). Recently, more aggressive therapies followed by autologous hemopoietic progenitor cell rescue, have also been successfully employed in these patients. However, this procedure, due to several factors including previous therapeutic regimens, is often limited by an inadequate collection of peripheral blood stem cell (PBSC). At present, very little data is available on the effect of FLUDA containing regimens in PBSC collection. We report our preliminary experience showing a possible correlation between FLUDA based chemotherapy regimens employed before mobilization and inability to collect an adequate number of blood derived hematopoietic progenitors for autologous PBSC transplantation in LG-NHL patients.     

膦甲酸钠预防及抢先治疗造血干细胞移植中巨细胞病毒感染的临床研究

目的 观察膦甲酸钠用于异基因造血干细胞移植(allo-HSCT)预防及抢先治疗巨细胞病毒(CMV)感染的疗效及安全性.方法 回顾性分析2014年10月至2016年12月96例接受allo-HSCT患者临床资料.采用实时荧光定量聚合酶链反应(RQ-PCR)监测患者血浆巨细胞病毒(CMV)-DNA情况至移植后6个月,预防及抢先治疗分别采用膦甲酸钠每天60 mg/kg和每天120 mg/kg.观察CMV血症、CMV病发生情况,分析CMV感染的影响因素,分析膦甲酸钠治疗效果和安全性,评估患者生存情况.结果96例患者中42例(43.8%)移植后发生CMV感染,中位感染时间42 d.膦甲酸钠治疗的42例CMV感染患者中,疗效显著36例(85.7%),进展为CMV病6例(14.3%),其中CMV转阴5例,因CMV间质性肺炎死亡1例.半相合移植及Ⅱ~Ⅳ度移植物抗宿主病(GVHD)患者CMV血症发病率升高(χ2=3.834,P<0.05;χ2=16.807,P<0.001).膦甲酸钠不良反应轻微,无明显中性粒细胞减少.发生CMV血症42例中,死亡12例(28.6%),未发生CMV血症54例中,死亡6例(11.1%),两组总生存率差异无统计学意义(χ2=3.546,P=0.06).结论 应用膦甲酸钠对allo-HSCT患者预防及抢先治疗CMV感染的疗效确切,耐受性良好,尤其适用于造血未完全恢复的患者.     

Humanized anti‐CD19 chimeric antigen receptor‐T cell therapy is safe and effective in lymphoma and leukemia patients with chronic and resolved hepatitis B virus infection

Chimeric antigen receptor‐T (CAR‐T) cell therapy is a promising treatment for CD19⁺ B‐cell malignancies. However, elimination of B cells by anti‐CD19 CAR‐T cells may lead to the reactivation of hepatitis B virus (HBV) and related hepatitis in patients with HBV infection. This study aims to evaluate the safety and efficacy of humanized anti‐CD19 CAR‐T (hCAR‐T) therapy in B‐cell malignancies with HBV infection. Twenty relapsed/refractory (r/r) diffuse large B‐cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL) patients with HBV infection were treated with hCAR‐T therapy. Among them, five hepatitis B antigen‐positive patients who received antiviral prophylaxis did not develop HBV reactivation, including two patients who received both hCAR‐T and allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Among 15 patients with resolved HBV infection, two received antiviral prophylaxis, and the other 13 did not experience HBV reactivation without antiviral prophylaxis. One patient with resolved HBV infection experienced HBV reactivation 6 months after hCAR‐T therapy and sequential allo‐HSCT. Moreover, HBV infection did not affect in vivo expansion of hCAR‐T cells or increase the risk of severe cytokine release syndrome. In conclusion, hCAR‐T therapy is safe and effective in DLBCL and ALL patients with chronic and resolved HBV infection under proper antiviral prophylaxis.     

儿童异基因造血干细胞移植后巨细胞病毒感染的危险因素分析

目的:分析儿童异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)后患者巨细胞病毒(cytomegalovirus,CMV)感染的发生率及其危险因素,为 CMV 感染的监测及治疗提供参考。方法:通过回顾性分析 2018年01月至 2020 年01月在郑州大学附属儿童医院血液肿瘤科、广州市妇女儿童医疗中心血液肿瘤科行异基因造血干细胞移植患者81例,应用χ2 检验及 Logistics 回归模型,分析 CMV 感染的发生率及其发生的危险因素。结果:81例患者中49例发生 CMV 感染,累计发生率为 60.4%,首次发生CMV感染的时间为移植后 37天（13~135天）,所有患者经抗病毒后转为阴性,转阴中位时间为14天（７~51天）。单因素分析提示,CMV感染的发生与性别、疾病类型、供体来源、Ⅰ-Ⅱ度急性移植物抗宿主病（acute graft versus host disease,aGVHD）无明显相关性（P＞0.05）,与Ⅲ-Ⅳ度aGVHD的发生呈明显相关性（P＜0.05）;多因素分析提示aGVHD的发生是CMV感染的危险因素。结论:Allo-HSCT后aGVHD的发生增加了CMV感染的发生率,是CMV感染的危险因素。     

Evolving paradigms in the treatment of newly diagnosed multiple myeloma

The treatment of multiple myeloma has undergone significant changes in the past few years. The introduction of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, has dramatically improved the outcome of this disease and considerably increased the treatment options available. Several trials have shown the advantages linked to the use of novel agents both in young patients, who are considered eligible for transplantation, and elderly patients, for whom a conventional therapy should be considered. These novel agents may increase the efficacy of autologous stem cell transplantation with deeper and long-lasting response. In the transplant setting, different novel agent combinations have proved to be superior to the traditional vincristine-doxorubicin-dexamethasone. Similarly, novel agents have also changed the treatment paradigm of patients not eligible for transplantation, thus replacing the traditional melphalan-prednisone approach. Preliminary data also support the role of consolidation and maintenance therapy to further improve outcomes. This article provides an overview of the latest strategies, including novel agents used to treat patients with multiple myeloma, both in the transplant and nontransplant settings.     

同期同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植治疗恶性血液病对比观察

目的 比较同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植(allo-HSCT)在恶性血液病治疗中的造血重建情况、移植相关并发症及临床疗效.方法 18例恶性血液病患者中,HLA同胞全相合9例、亲缘间单倍体相合9例,回顾性分析两组造血重建情况、移植相关并发症及临床疗效情况.结果 两组在造血重建、预处理相关毒性、急慢性移植物抗宿主病(GVHD)及临床疗效经改良预处理方案后无明显差异,但在移植过程中及术后、血制品的输注量、CMV感染率及真菌感染率发生方面,单倍体相合移植组明显高于同胞全相合组.结论 经改良预处理方案后同胞HLA全相合与亲缘间单倍体相合allo-HSCT在恶性血液病治疗方而临床疗效相近,亲缘间单倍体相合移植为恶性血液病治疗开辟了又一新途径,从根本上解决了供者来源问题.     

同期同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植治疗恶性血液病对比观察

 目的　比较同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植（allo-HSCT）在恶性血液病治疗中的造血重建情况、移植相关并发症及临床疗效。方法　18例恶性血液病患者中,HLA同胞全相合9例、亲缘间单倍体相合9例,回顾性分析两组造血重建情况、移植相关并发症及临床疗效情况。结果　两组在造血重建、预处理相关毒性、急慢性移植物抗宿主病（GVHD）及临床疗效经改良预处理方案后无明显差异,但在移植过程中及术后、血制品的输注量、CMV感染率及真菌感染率发生方面,单倍体相合移植组明显高于同胞全相合组。结论　经改良预处理方案后同胞HLA全相合与亲缘间单倍体相合allo-HSCT在恶性血液病治疗方面临床疗效相近,亲缘间单倍体相合移植为恶性血液病治疗开辟了又一新途径,从根本上解决了供者来源问题。     

同期同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植治疗恶性血液病对比观察

目的 比较同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植(allo-HSCT)在恶性血液病治疗中的造血重建情况、移植相关并发症及临床疗效.方法 18例恶性血液病患者中,HLA同胞全相合9例、亲缘间单倍体相合9例,回顾性分析两组造血重建情况、移植相关并发症及临床疗效情况.结果 两组在造血重建、预处理相关毒性、急慢性移植物抗宿主病(GVHD)及临床疗效经改良预处理方案后无明显差异,但在移植过程中及术后、血制品的输注量、CMV感染率及真菌感染率发生方面,单倍体相合移植组明显高于同胞全相合组.结论 经改良预处理方案后同胞HLA全相合与亲缘间单倍体相合allo-HSCT在恶性血液病治疗方而临床疗效相近,亲缘间单倍体相合移植为恶性血液病治疗开辟了又一新途径,从根本上解决了供者来源问题.     

同期同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植治疗恶性血液病对比观察

目的 比较同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植(allo-HSCT)在恶性血液病治疗中的造血重建情况、移植相关并发症及临床疗效.方法 18例恶性血液病患者中,HLA同胞全相合9例、亲缘间单倍体相合9例,回顾性分析两组造血重建情况、移植相关并发症及临床疗效情况.结果 两组在造血重建、预处理相关毒性、急慢性移植物抗宿主病(GVHD)及临床疗效经改良预处理方案后无明显差异,但在移植过程中及术后、血制品的输注量、CMV感染率及真菌感染率发生方面,单倍体相合移植组明显高于同胞全相合组.结论 经改良预处理方案后同胞HLA全相合与亲缘间单倍体相合allo-HSCT在恶性血液病治疗方而临床疗效相近,亲缘间单倍体相合移植为恶性血液病治疗开辟了又一新途径,从根本上解决了供者来源问题.     

同期同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植治疗恶性血液病对比观察

目的 比较同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植(allo-HSCT)在恶性血液病治疗中的造血重建情况、移植相关并发症及临床疗效.方法 18例恶性血液病患者中,HLA同胞全相合9例、亲缘间单倍体相合9例,回顾性分析两组造血重建情况、移植相关并发症及临床疗效情况.结果 两组在造血重建、预处理相关毒性、急慢性移植物抗宿主病(GVHD)及临床疗效经改良预处理方案后无明显差异,但在移植过程中及术后、血制品的输注量、CMV感染率及真菌感染率发生方面,单倍体相合移植组明显高于同胞全相合组.结论 经改良预处理方案后同胞HLA全相合与亲缘间单倍体相合allo-HSCT在恶性血液病治疗方而临床疗效相近,亲缘间单倍体相合移植为恶性血液病治疗开辟了又一新途径,从根本上解决了供者来源问题.     

同期同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植治疗恶性血液病对比观察

目的 比较同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植(allo-HSCT)在恶性血液病治疗中的造血重建情况、移植相关并发症及临床疗效.方法 18例恶性血液病患者中,HLA同胞全相合9例、亲缘间单倍体相合9例,回顾性分析两组造血重建情况、移植相关并发症及临床疗效情况.结果 两组在造血重建、预处理相关毒性、急慢性移植物抗宿主病(GVHD)及临床疗效经改良预处理方案后无明显差异,但在移植过程中及术后、血制品的输注量、CMV感染率及真菌感染率发生方面,单倍体相合移植组明显高于同胞全相合组.结论 经改良预处理方案后同胞HLA全相合与亲缘间单倍体相合allo-HSCT在恶性血液病治疗方而临床疗效相近,亲缘间单倍体相合移植为恶性血液病治疗开辟了又一新途径,从根本上解决了供者来源问题.     

同期同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植治疗恶性血液病对比观察

目的 比较同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植(allo-HSCT)在恶性血液病治疗中的造血重建情况、移植相关并发症及临床疗效.方法 18例恶性血液病患者中,HLA同胞全相合9例、亲缘间单倍体相合9例,回顾性分析两组造血重建情况、移植相关并发症及临床疗效情况.结果 两组在造血重建、预处理相关毒性、急慢性移植物抗宿主病(GVHD)及临床疗效经改良预处理方案后无明显差异,但在移植过程中及术后、血制品的输注量、CMV感染率及真菌感染率发生方面,单倍体相合移植组明显高于同胞全相合组.结论 经改良预处理方案后同胞HLA全相合与亲缘间单倍体相合allo-HSCT在恶性血液病治疗方而临床疗效相近,亲缘间单倍体相合移植为恶性血液病治疗开辟了又一新途径,从根本上解决了供者来源问题.     

同期同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植治疗恶性血液病对比观察

目的 比较同胞HLA全相合与亲缘间单倍体相合异基因造血干细胞移植(allo-HSCT)在恶性血液病治疗中的造血重建情况、移植相关并发症及临床疗效.方法 18例恶性血液病患者中,HLA同胞全相合9例、亲缘间单倍体相合9例,回顾性分析两组造血重建情况、移植相关并发症及临床疗效情况.结果 两组在造血重建、预处理相关毒性、急慢性移植物抗宿主病(GVHD)及临床疗效经改良预处理方案后无明显差异,但在移植过程中及术后、血制品的输注量、CMV感染率及真菌感染率发生方面,单倍体相合移植组明显高于同胞全相合组.结论 经改良预处理方案后同胞HLA全相合与亲缘间单倍体相合allo-HSCT在恶性血液病治疗方而临床疗效相近,亲缘间单倍体相合移植为恶性血液病治疗开辟了又一新途径,从根本上解决了供者来源问题.     

Clinical outcome of peripheral blood stem cell support

Two clinical results of peripheral blood stem cell support are commonly considered: (1) the effect on hematopoietic recovery and (2) the effect on the underlying malignancy. The dynamics of hematopoietic recovery after autoiogous bone marrow transplantation and after autologous peripheral blood stem cell transplantation in a clinical setting are similar if no exogenous cytokines are administered and the peripheral stem ceils are collected while their numbers are not deliberately increased (mobilised). If mobilized peripheral stem cells are transplanted, hematopoietic recovery is accelerated. In some circumstances, patients who receive peripheral stem cell transplantation may experience an improved progression-free survival after high-dose therapy when compared with similar patients who receive autologous bone marrow transplantation. Explanations for such a survival advantage might include (1) a lower likelihood of occult tumor cells capable of restoring disease in peripheral stem cell autograft products than in bone marrow harvests, (2) a greater number of cytotoxic effector cells capable of destroying occult tumor ceils in the peripheral stem cell collections than in bone marrow harvests, and (3) a different and advantageous pattern of immunologic recovery following autologous peripheral stem cell transplant compared to autologous bone marrow transplant.