再生障碍性贫血无关供者造血干细胞移植治疗进展

 近年随着预处理方案的改良、人类白细胞抗原（HLA）精确配型的实施以及新型强力广谱抗生素的应用,非HLA相合同胞供者干细胞移植治疗再生障碍性贫血（AA）疗效明显提高。研究证实年轻患者一次免疫抑制治疗无效,行无关供者造血干细胞移植的可行性及有效性、移植排斥、移植物抗宿主病（GVHD）和感染并发症等都得到极大改善。与免疫抑制治疗相比,年轻重型AA患者二次治疗采用无关供者造血干细胞移植可获更高的无病生存率。     

造血干细胞移植研究和应用的回顾与展望

 结合第54届美国血液学会年会教育论坛的相关内容着重复习造血干细胞移植（HSCT）领域的一些进展。在论述人类白细胞抗原（HLA）配型技术和供者来源扩展的基础上,分别简述了各类HSCT（HLA-相合同胞供者移植、脐带血移植、无关供者移植、 HLA-单倍型相合的移植）疗效的提升,也回顾了疾病种类和病期对HSCT结局的影响;结合自身的理解与经验,强调确保供者安全的注意事项与意义。     

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。     

乙肝病毒感染供者来源异基因间充质干细胞联合非清髓性造血干细胞移植治疗骨髓增生异常综合征-难治性贫血一例

 目的　进一步探讨骨髓增生异常综合征-难治性贫血（MDS-RA）患者采用异基因造血干细胞移植的安全性、有效性、可行性等;联合应用供者来源间充质干细胞（MSC）移植,进一步了解MSC在造血重建和免疫抑制方面的作用;探讨移植过程中供者来源乙肝的有效预防措施。方法　MDS-RA患者选用合适的预处理及移植物抗宿主病（GVHD）预防方案,移植前体外分离、培养、扩增供者来源MSC,供者经粒细胞集落刺激因子（G-CSF）动员后在回输当日采集外周血造血干细胞,造血干细胞回输前4 h先行回输MSC。供者来源乙肝处理：供者在移植前1个月开始抗病毒治疗;受者移植前2个月起予乙肝疫苗接种,移植前1周予高效价乙肝免疫球蛋白应用,移植1个月后起预防性抗病毒药物治疗,全程定期检测受者乙肝病毒表面抗原、e抗体、核心抗原、雅培乙肝表面抗体滴度等指标,根据乙肝表面抗体滴度及时补充高效价乙肝免疫球蛋白。结果　移植后+10天患者造血重建,造血重建前未出现严重感染、出血等情况,无急慢性GVHD发生。移植后＋30天骨髓细胞学示：各系增生活跃,巨核细胞9个,血小板小簇可见;荧光原位杂交技术（FISH）检测性染色体：XY 47／300。移植后+90天FISH检测：XY 7／300。移植后+60天HBV-DNA外周血和骨髓标本均阴性,HBsAb阳性,HBsAb滴度持续大于100,+60天时达800。患者继续随访中,血象正常,生活质量良好。结论　初步证实同胞来源异基因造血干细胞联合MSC移植救治MDS-RA方法可行且安全有效,临床有待更多病例积累。采用乙肝疫苗接种、高效价免疫球蛋白应用联合预防性抗病毒治疗的综合防治措施,有效预防受者感染供者来源乙肝,可供类似病例借鉴。     

造血干细胞移植治疗血液肿瘤50例临床分析

 【摘要】　目的　了解造血干细胞移植在血液系统疾病临床治疗中的临床疗效。方法　对50例造血干细胞移植患者的临床资料进行回顾分析。结果　全组移植总计成功率92 %,预计2年总生存（OS）率为60 %。按移植干细胞来源不同统计2年生存率情况：同胞全合组72.2 %,亲缘间单倍体相合组57.9 %,自体造血干细胞移植组38.5 %。按移植病种不同统计2年生存率情况：慢性粒细胞白血病慢性期（CML-CP）83.3 %、骨髓增生异常综合征（MDS）75.0 %、CML进展期66.7 %、急性髓系白血病（AML）66.7 %、恶性淋巴瘤50.0 %、重症再生障碍性贫血（SAA）50.0 %、急性淋巴细胞白血病（ALL）28.6 %、多发性骨髓瘤（MM）0。结论　依据患者的疾病不同合理选择移植适应证及移植术式,可使更多的移植患者从中受益。     

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.     

Allogeneic stem cell transplantation for myelodysplastic syndromes: critical for cure?

Allogeneic stem cell transplantation (SCT) is the treatment of choice for young patients (age ≤ 55 years) with myelodysplastic syndromes (MDS) characterized by poor-risk or intermediate-risk cytogenetics, who have a histocompatible related or unrelated donor. For patients who lack an human leukocyte antigen-compatible donor, autologous SCT, or chemotherapy may be good alternatives for those with MDS and with good-risk cytogenetic characteristics. Iron toxicity is an underestimated cause of hematopoietic stem cell transplantation (HSCT) treatment-related mortality. The pathogenesis, diagnosis, and monitoring of iron-induced organ damage are currently topics of investigation. Prospective studies on the prevention or treatment of iron toxicity before HSCT and/or after HSCT are necessary.     

Allogeneic cellular gene therapy for hemoglobinopathies

Hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for patients with thalassemia major and sickle cell disease (SCD). Current myeloablative treatment protocols allow the cure of 78% to 90% of patients with thalassemia and 72% to 96% with SCD, depending on disease status at the time of transplantation. The major limitation to successful transplantation is the lack of a suitable HLA-matched family donor. Unrelated donor HSCT is now extensively used to treat thalassemia, with results similar to those obtained following transplantation using HLA-matched sibling donors. Patients who lack a matched related or unrelated donor can now benefit from successful transplantation using haploidentical donors.     

非血缘及HLA配型不合造血干细胞移植的临床研究

 目的 探讨非血缘及HLA配型不全相合造血干细胞移植在白血病治疗中的应用。方法非血缘脐血移植治疗儿童白血病3例,非血缘异基因外周血造血干细胞移植治疗白血病1例,HLA配型不全相合外周血造血干细胞移植治疗白血病1例。结果 5例患者完全植入,+15～+25天白细胞（WBC）＞1.0×109／L-1,＋35～＋51天血小板（Plt）＞20×109／L-1。例1出现急性移植物抗宿主病（aGVHD）Ⅰ度;例4 aGVHD Ⅳ度;例5出现肝静脉闭塞综合征（VOD）、aGVHDⅠ度、出血性膀胱炎（HC）;例2移植后6个月复发,放弃治疗死亡;余4例正常生活或工作。结论　非血缘及HLA配型不全相合造血干细胞移植治疗白血病是安全有效的。     

Perspective on the role of haploidentical transplantation in the management of hematologic malignancies: Why do it?

Haploidentical hematopoietic stem cell transplantation (HSCT) using mismatched family member donors has historically been complicated by high rates of nonrelapse toxicity and the need for laboratory expertise in depleting grafts of T lymphocytes. Over the past decade, improvements in supportive care, the increased use of peripheral-blood stem cell grafts, and improved T-cell depletion techniques have reduced the incidence of graft failure and lowered the rate of nonrelapse mortality. In addition, clinical studies have demonstrated that the donor-recipient mismatch may be beneficial in this setting, stimulating an immunologic cell-mediated antileukemia effect that results in lower disease recurrence rates. All of these advances have led to improvements in outcomes following haploidentical HSCT, making it an attractive option available to some patients. Because most patients do not have a matched related donor available and time to identify an unrelated donor may be excessive, haploidentical HSCT is a potentially curative option for these patients.     

Advances in pediatric hematopoietic stem cell transplantation

Allogeneic and autologous hematopoietic stem cell transplantation (HSCT) has become a therapeutic option for an increasing number of patients with otherwise incurable leukemias, solid tumors, immunodeficiencies, hemoglobinopathies and metabolic diseases. For patients requiring an allogeneic transplant, the addition of unrelated cord blood units and partially matched family member donors as alternate stem cell sources has increased the chances that an appropriate donor can be identified. In addition, new approaches to stem cell graft engineering are yielding insights into potential cellular immune therapies, which may decrease the adverse effects of HSCT such as graft-versus-host disease (GVHD) and harness the alloimmune graft-versus-leukemia effect. Novel conditioning regimens, primarily reduced intensity and non-myeloablative regimens, allow patients with significant co-morbidities to undergo transplantation with reduced morbidity and mortality. Combinations of immune-modulatory cytokines and monoclonal antibodies with autologous and allogeneic transplantation are among the advances being explored in contemporary HSCT.     

骨髓增生异常综合征和再生障碍性贫血患者异基因造血干细胞移植的时机选择:第56届美国血液学会年会报道

介绍第56届美国血液学会(ASH)年会关于骨髓增生异常综合征(MDS)和再生障碍性贫血(AA)患者进行异基因造血干细胞移植的时机选择的报道.同种异体造血干细胞移植(HSCT)治疗MDS是疾病治愈的有效途径,但病死率也很高.对于低危和中危-Ⅰ MDS患者,应尽量延后HSCT的应用时间.但是对中危-Ⅱ和高危MDS患者,在确诊后应尽快进行HSCT,其生存期明显优于延后HSCT的患者.HSCT前的预处理方案可以选择阿扎胞苷、白血病形式的诱导化疗或联合以上2种治疗.HSCT已被证实可以治愈重型AA,但新诊断的患者中HLA相合的同胞供者仅占1/4.总之,HLA匹配的相关和无关供者HSCT会成为大多数高危MDS和初发重型AA的治疗选择.     

造血干细胞移植治疗慢性髓系白血病的疗效分析

背景与目的：慢性髓系白血病(chronic myelogenous leukemia,CML)是一种常见的恶性血液疾病,造血干细胞移植(hematopoietic stem cells transplantation,HSCT)是治疗CML最主要的手段。本研究评价自体(auto-)或异体(allo-)HSCT治疗CML的临床疗效。方法：44例CML息者接受HSCT治疗,其中8例采用净化auto-HSCT,30例采用相关allo—HSCT,6例采用无关allo-HSCT;预处理方案：31例接受TBI CY(全身放疗 环磷酰胺)方案,12例采用改良BuCY(羟基脲、马利兰、阿糖胞苷、环磷酰胺)方案,1例采用MACC(马法兰、阿糖胞苷、环磷酰胺、环已亚硝脲)方案;移植物抗宿主病(GVHD)预防：相关移植采用CsA MTX(环孢素A 甲氨蝶呤)方案,无关移植采用CsA MTX MMF(霉酚酸酯) ATG(抗胸腺细胞球蛋白)方案。此外,移植前加速期和急变期患者单用CsA。Kaplan—Meier生存模型评估移植后无病生存。结果：8例接受激活骨髓(ABM)联合反义寡核苷酸或联合STI571体内外净化auto-HSCT后,除1例死于移植中相关并发症外,其余均获得部分或完全细胞或分子遗传学缓解,其中1例急变期患者血液学完全缓解(CR)后移植获分子遗传学CR达81个月。36例allo—HSCT患者除1例死于肝静脉闭塞综合征(hepatic veno-occlusive disease,VOD)和1例移植前急变患者移植后无效以外,其余患者均获CR。移植中感染发生率为38．6％,VOD发生率为9．1％,出血性膀胱炎(hemorrhagic cystitis,HC)发生率为15．9％,巨细胞病毒(CMV)性肺炎为11．4％,VOD、HC和CMV肺炎均发生在allo-HSCT患者。急性GVHD发生率在相关与无关移植中分别为40．0％与33．3％。在相关移植中慢性GVHD发生率为43．4％。移植相关死亡率在自体与异体HSCT中分别为12．5％与16．7％,auto—HSCT复发率为37．5％,相关allo-HSCT复发率为13．3％。移植后5年无病生存率在自体与相关异体移植中分别为18．7％与53．7％。移植前慢性期与加速期和急变期患者相关allo-HSCT后5年无病生存率分别为66．4％与26．7％。结论：allo—HSCT对CML患者,尤其是慢性期患者具有较高的临床治愈率;CsA MTX MMF ATG四联方案在无关allo-HSCT中应用能降低移植后急性GVHD的发生率及程度;采用净化骨髓自体移植能延长CML患者生存期,甚至少部分患者可获得临床治愈。     

Treatment of Relapse of Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

Disease relapse remains a major cause of mortality for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Historically, patients who experience disease relapse after HSCT have a dismal prognosis with very few long-term survivors. There is no standard treatment for patients in this situation given the variability in patient characteristics, disease biology, complications such as graft-vs.-host disease (GVHD) and infections, donor availability, and patient choice. Here, we discuss the current options for treatment of relapsed AML after HSCT including conventional chemotherapy, novel agents, donor leukocyte infusion, second allogeneic HSCT, and emerging therapies.     

Donor Lymphocyte Infusions After Allogeneic Transplantation: A Single-Center Experience

Allogeneic hematopoietic cell transplantation (AHCT) represents the only curative therapy for many hematological malignancies. The graft versus leukemia effect, driven by donor T cells, plays a major role in its curative potential. This effect is sometimes very evident when patients with acute myeloid leukemia and myelodysplasia relapse after AHCT and are treated with donor lymphocyte infusions (DLIs). We retrospectively reviewed the charts of 64 patients who received DLI between 2012 and 2017 in our center. The mean age of the patients was 59 years (range, 34-79). Fifty percent were male (n = 32). The mean follow-up time after AHCT was 50.17 months (range, 8-174). The indication for DLI were disease progression, mixed chimerism, minimal residual disease, and other etiologies in 43.8%, 40.7%, 14%, and 1.5% of patients, respectively. The most common diagnosis was acute leukemia, followed by multiple myeloma. Of all patients, 59.4% received a transplant from a related donor, 39% received a transplant from an unrelated donor, and 1.6% received a transplant from a haploidentical donor. Reduced-intensity conditioning AHCT was the most frequent regimen used (53%). DLI was given alone in 79.7% of patients. Prophylactic DLI was given at 30 days after transplantation in patients who received human leukocyte antigen (HLA)-matched related human stem cell transplantation (HSCT) or 45 to 60 days post-transplant in patients receiving haploidentical HSCT or HLA-matched unrelated HSCT. Patients were treated without graft versus host disease (GVHD) prophylaxis. The use of DLI after transplantation remains a feasible procedure with rates of response >60%. Moreover, DLIs are well tolerated with a GVHD rate <10% in our series. We can hypothesize that in our experience the efficacy of this strategy does not rely on the induction of GVHD.     

Reverse seroconversion of hepatitis B virus after hematopoietic stem cell transplantation

Hepatitis B virus (HBV) reactivation in patients previously positive for hepatitis B surface antibody (HBsAb), so-called reverse seroconversion, has been considered to be a rare complication after hematopoietic stem cell transplantation (HSCT). We experienced two patients who developed reverse seroconversion among nine who were HBsAb positive and Hepatitis B core antibody (HBcAb) positive before HSCT; one after autologous bone marrow transplantation (BMT) and another after allogeneic peripheral blood stem cell transplantation (PBSCT). We reviewed the literature and considered that reverse seroconversion of HBV after HSCT is not uncommon among HBsAb positive recipients. The use of corticosteroids, the lack of HBsAb in donor, and a decrease in serum HBsAb and HBcAb levels may predict reverse seroconversion after HSCT.