异基因外周血干细胞移植治疗骨髓增生异常综合征一例

骨髓增生异常综合征（MDS）是造血系统的一组恶性疾病，治疗MDS的目的是清除或减少异常细胞克隆，部分或全部重建正常造血，或诱导细胞向正常分化、成熟，但限于MDS发病机制的异质性，不同MDS患者差异较大，临床治疗技术进展较为缓慢。目前除异基因造血干细胞移植外，尚无根治此病的方法。我院为1例MDS患者施行异基因外周血干细胞移植，现将诊治情况报告如下。     

异基因外周血干细胞移植治疗骨髓增生异常综合征一例

骨髓增生异常综合征（MDS）是一种起源于多能造血干细胞的克隆异常增殖性疾病，治疗反应差，易发展为急性白血病。造血干细胞移植是目前惟一可治愈该病的方法。我科于2004年9月对1例MDS患者行异基因外周血干细胞移植，取得了较好的效果，现报告如下。     

增强预处理方案的造血干细胞移植对骨髓增生异常综合征的治疗效果

目的 评价采用去甲氧柔红霉素增强预处理方案的外周血造血干细胞移植对骨髓增生异常综合征的治疗效果.方法 2004年8月至2009年7月,采用去甲氧柔红霉素(IDA)+白消安(Bu)+环磷酰胺(Cy)的增强预处理方案对12例骨髓增生异常综合征患者进行了外周血造血干细胞移植.具体用法为:IDA 15 mg/m~2,每天持续静脉滴注20 h(移植前12 d～移植前10 d给予);Bu 0.8mg/kg,每6 h静脉滴注1次(移植前6 d～移植前4 d给予);Cy 1.8 g/m~2,静脉滴注(移植前3 d～移植前2 d给予).采用环孢素A(CsA)联合短程甲氨碟呤(MTX)预防急性移植物抗宿主病(aGVHD).结果 12例受者均移植成功,对该预处理方案耐受良好.8例受者存活,总存活率为66.7%,无病存活率为58.3%,2例受者原发病复发.以世界卫生组织(WHO)亚型分组和国际预后积分系统(IPSS)分组显示,总存活率的组间比较,差异均无统计学意义.结论 采用去甲氧柔红霉素增强预处理方案的外周血造血干细胞移植对治疗骨髓增生异常综合征有效,且复发率低.     

减低强度预处理异基因造血干细胞移植治疗高危骨髓增生异常综合征的效果

目的 探讨减低强度预处理异基因造血干细胞移植(allo-HSCT)治疗高危骨髓增生异常综合征(MDS)的疗效和安全性.方法 应用减低强度预处理allo-HSCT治疗2012年1月至2014年1月我科收治的10例高危骨髓增生异常综合征患者,其中男6例,女4例,平均年龄30.3岁,确诊至移植的中位时间为4.5个月,7例为HLA配型全相合,3例为HLA配型不合,供者接受粒细胞集落刺激因子动员,采用骨髓加外周血干细胞联合移植,预处理方案为降低预处理强度氟达拉滨(FLU)、环磷酰胺(CTX)及抗人淋巴细胞免疫球蛋白(ATG),移植物抗宿主病(GVHD)预防采用联合免疫抑制剂(包括环孢素A、氨甲蝶呤等).移植后观察全部患者毒副反应、GVHD和无病生存等情况.结果 全组患者均获造血重建,中性粒细胞≥0.5×109/L及血小板≥20×109/L的平均时间分别为分别19.7d及23.8d,植入证据检测为100％完全供者造血.随访至2014年10月,中位随访时间20.5个月(8～32个月).2例患者死于复发,并发症死亡1例,其他患者目前仍处于完全缓解状态,无病生存率达到70％,最长无病生存时间已达32个月.结论 Allo-HSCT是治疗高危MDS的可行方法,疗效好、安全系数大,可在临床广泛开展.     

异基因外周血干细胞移植治疗骨髓增生异常综合征8例临床分析

观察异基因外周血干细胞移植(allogeneic peripheral blood stem cell transplantation,allo-PBSCT)治疗骨髓增生异常综合征(myelodysplastic syndrome,MDS)的疗效.方法 对2007年5月至2012年1月在中山大学附属第三医院血液科住院的8例MDS患者采用allo-PBSCT治疗.其中男2例,女6例,年龄18 ~ 50岁(中位年龄31岁).按世界卫生组织(World Health Organization,WHO)MDS分型标准(2008年)分类,难治性细胞减少伴多系增生异常(refractory cytopenia with multilineage dysplasia,RCMD)占2例,难治性贫血伴原始细胞增多(refractory anemia with excess blasts,RAEB)-1占1例,RAEB-2占3例,MDS进展为急性髓系白血病(MDS-AML)占2例.供者经粒细胞集落刺激因子(granulocyte colony-stimulating factor,G-CSF)5 ~10 μg/(kg·d)动员5d后,分1~2d采集外周血造血干细胞.受者输入外周血单个核细胞(5.8~11.6)×108/kg(中位数7.7×108/kg).受者预处理方案为BuCy方案6例,改良BuCy方案2例,非亲缘供者联合使用抗胸腺细胞球蛋白(ATG).予环孢素加短疗程甲氨蝶呤方案预防移植物抗宿主病(GVHD).结果 8例患者中有6例移植后造血重建,中性粒细胞≥0.5×109/L和血小板≥20×109/L的时间分别为移植后9~15d(中位数12d)及11~42 d(中位数13d);4例患者发生急性移植物抗宿主病(aGVHD),其中I度1例,Ⅱ度2例,Ⅳ度1例;存活超过l00d的6例患者发生局限型慢性移植物抗宿主病3例.随访时间为2.6~56.9个月(中位数27.0个月),2例患者移植后100 d内死亡,其余患者均无病存活.以Kaplan-Meier法估算,患者总体生存率及无病生存率均为(75.0±15.3)%,生存期为(43.4±8.3)个月.结论 外周血干细胞移植是治疗年轻MDS患者的有效方法.     

降低骨髓增生异常综合征患者异基因造血干细胞移植后移植相关死亡率和复发率的方案

骨髓增生异常综合征（myelodysplastic syndrome,MDS）是一组以髓内原始细胞显著增多、外周血细胞减少以及血液和骨髓形态学异常、增生为特征的异质性克隆性干细胞疾病。异基因造血干细胞移植是最有可能治愈MDS的方法之一,但仍有超过50％的患者存在疾病复发或移植相关死亡的问题。本文就降低异基因造血干细胞移植治疗MDS后的移植相关死亡率（transplant related mortality,TRM）和复发率的治疗方案做一探讨。     

降低高危骨髓增生异常综合征异基因造血干细胞移植后复发的策略研究

目的从优化预处理和桥接治疗两个角度探索降低高危骨髓增生异常综合征(MDS)异基因造血干细胞移植(allo-HSCT)术后复发的策略。方法对2013年1月至2019年9月于华中科技大学同济医学院附属协和医院血液病研究所接受allo-HSCT的84例高危MDS患者进行回顾性分析。按使用的预处理方案分为:地西他滨强化预处理组49例, BUCY2预处理组35例;按移植前是否接受治疗分为:移植前治疗组34例, 未治疗组50例。比较患者造血重建、移植物抗宿主病(GVHD)、复发率、移植相关死亡率(TRM)、存活率的差异。结果地西他滨强化组与BUCY2组相比, 造血重建、TRM和急、慢性GVHD发生情况差异无统计学意义;复发率明显低于BUCY2组(18.7%比40.0%, P=0.025), 生存显著优于BUCY2组(3年总存活率:71.3%比51.2%, P=0.038;3年无病生存率:65.3%比45.2%, P=0.033)。此外, 移植前桥接治疗组复发率明显低于未治疗组(20.7%比38.9%, P=0.035), 3年总存活率及无病生存率显著优于未治疗组(71.2%比50.8%, P=0....     

防控急性白血病与骨髓增生异常综合征异基因造血干细胞移植后复发

通过早期识别高危因素, 优化诱导、巩固或桥接治疗, 选择优化预处理方案, 防控异基因造血干细胞移植后复发。     

异基因造血干细胞移植患者术后并发脑脓肿的护理

对1例骨髓增生异常综合征患者行异基因造血干细胞移植,术后并发脑脓肿。对患者加强护理,即密切监测患者病情,及时发现症状并采取对应的护理措施,包括颅内压增高的护理、肢体运动障碍的护理、发热(抗感染)的护理、心理护理、预防出血的护理、并发症的观察。结果患者移植成功,脑脓肿得到有效控制,顺利出院。提出避免引起颅内压增高的因素、控制感染、预防出血、促进造血重建,为患者制订个体化的康复计划,可使脑脓肿得到控制,促进康复。     

自体造血干细胞移植后序贯异基因造血干细胞移植治疗浆母细胞淋巴瘤一例

正浆母细胞淋巴瘤(plasmablastic lymphoma,PBL)是一种罕见的非霍奇金淋巴瘤,来源于B细胞,侵袭性高、预后差,具有独特的临床特征。宁波市第一医院血液科采用自体造血干细胞移植(autologous hematopoietic stem cell transplantation,auto-HSCT)后序贯异基因造血干细胞移植(allogeneic     

Second allogeneic hematopoietic stem cell transplantation: a treatment for graft failure

We evaluated the results in 20 recent patients treated with a second hematopoietic stem cell transplantation (HSCT) after graft failure (GF). There were 10 children <18 yr of age. Ten patients had a non-malignant disease, and the other 10 had a malignant disease. In most of the transplantations, fludarabine-based reduced intensity conditioning (RIC) was given. Bone marrow was given to 11 patients, peripheral blood system cell (PBSC) in seven and cord blood to two patients. For the second transplantation (n = 20), a new donor was used in nine cases, while the initial donor was used in 11 transplants. Eight patients (40%) suffered from a second GF. Five of these patients were treated with a third HSCT. The probability of survival was 65% one yr and 60% three yr after the second HSCT. No difference in survival was found between patients transplanted with a new donor (56%) compared to those using the original donor (64%). The three-yr survival was 70% for children compared to 50% for adults (p = ns). Patients with a non-malignant disorder showed a three-yr survival of 90% compared to 20% in patients with a malignant disease (p = 0.005). We concluded that re-transplantation using RIC is a valid option for GF, especially in patients with non-malignant disorders.     

The significance of cytomegalovirus viremia at day 100 or more following allogeneic hematopoietic stem cell transplantation

We conducted a single‐center retrospective review of patients who had received allogeneic hematopoietic stem cell transplantation (HSCT) between January 2003 and December 2007, to assess the incidence and risk factors for late CMV infection and evaluate its effects on outcomes. Twenty of 49 HSCT recipients (41%) developed CMV infection at day ≥100 after transplant. Univariable analysis showed that having a matched unrelated donor, having early CMV infection, having a diagnosis of lymphoma, and receipt of antithymocyte globulin were risks for developing late CMV. On multivariable analysis, the occurrence of CMV prior to day 100 and lymphoma conferred a significant risk for late CMV infection. Of the 20 patients with late CMV infection, two patients manifested CMV disease (10%). Despite the relatively low incidence of CMV disease, patients with late CMV infection had a 4.8‐fold increased risk of death compared to patients without late CMV. Identifying patients at increased risk for developing late CMV infection may be important for prompting more intensive monitoring of infection late after HSCT, particularly because this manifestation of CMV is associated with poorer outcomes.     

Nonmyeloablative stem cell transplantation and cell therapy for malignant and non-malignant diseases

The conditioning prior to allogeneic stem cell transplantation was originally designed as a myeloablative conditioning, designed to eliminate malignant or genetically abnormal cells and then use the transplant procedure for rescue of the patients or to replace missing bone marrow products. However, allografts can induce effective graft vs. malignancy effects and can also eliminate undesirable hematopoietic stem cells in patients with genetic disorders and autoimmune diseases, thus documenting that alloreactive effects mediated by donor lymphocytes post-grafting can play a major role in eliminating hematopoietic cell of host origin, as well as provide effective immunotherapy for the treatment of disease recurrence. The efficacy of donor lymphocyte infusion (DLI) could be improved by activation with rIL-2 or by donor immunization. The cumulative experience over the years suggesting that alloreactive donor lymphocytes were most effective in eliminating tumor cells of host origin resulted in an attempt to reduce the intensity of the conditioning in preparation for the transplant procedure used for the treatment of hematological and other malignancies as well as life-threatening non-malignant disorders for which allogeneic stem cell transplantation may be indicated. Our working hypothesis proposed that the myeloablative conditioning which is hazardous and may be associated with early and late side effects, may not be required for treatment of patients with any indication for allogeneic stem cell transplantation. Instead, nonmyeloablative conditioning based on the use of reduced intensive preparatory regimen, also known as nonmyeloablative stem cell transplantation, may be sufficient for engraftment of donor stem cells while avoiding procedure-related toxicity and mortality, followed by elimination of undesirable cells of host origin by post-transplant effects mediated by alloreactive donor lymphocytes infused along with donor stem cells or administered subsequently as DLI. Improvement of the immediate outcome of stem cell transplantation using NST due to a significant decrease in transplant related mortality has broadened the spectrum of patients eligible for allogeneic stem cell transplantation, including elderly patients and other patients with less than optimal performance status. Likewise, the safer use of stem cell transplantation prompted expanding the scope of potential indications for allogeneic stem cell transplantation, such as metastatic solid tumors and autoimmune disorders, which now are slowly becoming much more acceptable. Current strategies focus on the need to improve the capacity of donor lymphocytes to eliminate undesirable malignant and non-malignant hematopoietic cells of host origin, replacing abnormal or malignant stem cells or their products with normal hematopoietic stem cells of donor origin, while minimizing procedure-related toxicity and mortality and improving the quality of life by reducing the incidence and severity of hazardous acute and chronic GVHD.     

Myeloablative allogeneic hematopoietic stem cell transplantation in elderly patients

This study aimed to evaluate the outcome following myeloablative allogeneic hematopoietic stem cell transplantation (SCT) among patients older than 50 yr of age. A total of 215 patients with a median age of 57 yr underwent allogeneic hematopoietic SCT for early (41%) or advanced (59%) hematologic malignancies. After a median follow-up of 36 months a 10-yr survival estimate of 56 +/- 6% could be assessed for patients in early disease stages while patients with advanced diseases showed a significantly decreased survival probability of 31 +/- 5% (p < 0.0002). Transplant related mortality (TRM) at day 100 and 365 post-transplant was 13% and 30% for early but increased to 21% and 49% for advanced disease stages. As major determinants of TRM advanced disease stage (p < 0.0001) and occurrence of grades II-IV graft-vs.-host disease (GVHD) (p < 0.0001) were identified. These results show that hematopoietic SCT following myeloablative conditioning is also applicable to elderly patients whereas disease stage and high-grade GVHD represent the essential prognostic factors for outcome.     

造血重建对异基因造血干细胞移植患者早期生活质量的影响

目的探讨造血重建对异基因造血干细胞移植(HSCT)患者早期生活质量的影响,为针对性干预提供参考。方法将122例患者以出净化病房时血小板是否重建分为造血重建组(88例)和造血延迟组(34例),采用癌症治疗功能评价系统-骨髓移植生命质量测评量表(FACT-BMT)测评患者在入净化病房前、移植后1、3、6个月生活质量。结果 122例患者不同时间点生活质量得分差异有统计学意义,其中移植后1个月得分最低,6个月时得到显著改善(P<0.05,P<0.01);造血重建组前3个时间点生活质量得分显著高于造血延迟组(均P<0.05)。多元回归分析结果显示早期造血重建与否是HSCT患者生活质量的主要影响因素,其次为移植物抗缩主病及性别(均P<0.05)。结论早期造血重建可作为HSCT患者术后生活质量的预测因素,护理人员应特别注重对造血延迟患者的针对性护理,以助HSCT患者在术后早期获得较好的生活质量。     

Comparative outcomes of reduced intensity and myeloablative allogeneic hematopoietic stem cell transplantation in patients under 50 with hematologic malignancies

We have conducted a direct comparison of the outcomes of reduced intensity and myeloablative conditioning in younger adults with hematological malignancies<50 yr. One hundred and five patients received transplants from human leukocyte antigen (HLA)-matched donors, via either reduced intensity (n=35) or myeloablative conditioning (n=70). The median ages of the reduced intensity and myeloablative groups were 36 and 33 yr (p=0.014). Neutrophil engraftment (i.e. time to absolute neutrophil count>0.5x10(9)/L) occurred more rapidly in the reduced intensity group (median: 10 d; range: 0-21 d) than in the myeloablative group (median: 18 d; range: 11-38 d; p<0.0001). The incidence of grades 2-4 acute graft-vs.-host disease were similar between the reduced intensity and myeloablative groups, at 17% vs. 24% respectively (p=0.40). The cumulative incidence of day 100 non-relapse mortality was 18% in the reduced intensity group, and 21% in the myeloablative group (p=0.88). The overall two-yr survival rates were 43% in the reduced intensity group, and 35% in the myeloablative group (p=0.72). In conclusion, reduced intensity transplantation yielded outcomes comparable with those of myeloablative transplantation in patients under 50 with hematological malignancies.