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。     

造血干细胞移植治疗恶性血液病临床研究

 目的 探讨造血干细胞移植（HSCT）治疗恶性血液病的临床疗效及并发症的防治。方法51例急慢性白血病、恶性淋巴瘤、多发性骨髓瘤患者中,36例选择自体造血干细胞移植（auto-HSCT）,15例接受异基因造血干细胞移植（allo-HSCT）,包括HLA不全相合3例及非血缘关系移植4例,混合移植2例;预处理自体移植主要选用CBV,BEAC方案,异基因移植采用BU／CY2及改良的BU／CY方案;移植物抗宿主病（GVHD）的预防采用CsA+MTX或CsA+MTX＋MMF方案。结果 51例患者中49例获得造血重建,在auto-HSCT和allo-HSCT后WBC≥1.0×109／L的中位时间分别为13 d和17 d,血小板≥20×109／L的中位时间分别为21和25 d;40 ％出现aGVHD,26.7 ％出现cGVHD;3.9 %出现HVOD;出血性膀胱炎发生率5.9 ％;CMV感染发生率33.3 ％;62.7 ％出现黏膜炎;54.9 ％出现不同部位的感染;移植相关死亡率3.5 %,随访3～95个月,移植后复发11例,其中auto-HSCT 9例,allo-HSCT 2例。结论 HSCT是目前治疗恶性血液病的最佳方法,但移植期间需要进一步探索如何减少其相关并发症,以提高血液肿瘤的治愈率及延长患者的无病生存时间。     

Imatinib combined with myeloablative allogeneic hematopoietic stem cell transplantation for advanced phases of chronic myeloid leukemia

To evaluat the efficacy and safety of myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with imatinib for advanced chronic myeloid leukemia (CML), 15 patients with accelerated phase (n = 6) or blast crisis (n = 9) were enrolled in this study. All the patients were conditioned with cyclophosphamide and busulfan, and treated with cyclosporin (CsA)/methotrexate (MTX)/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. Eleven of these 15 patients (73.3%) achieved complete hematologic response to pre-transplant imatinib, and six (40%) achieved a cytogenetic response. No engraftment failure was observed and the early transplant-related mortality was only 6.7%. Grade 3/4 acute GVHD occurred in 13.3% of patients. Chronic GVHD was observed in 61.5%, including 23.1% suffered from extensive disease. The 5-year estimated rates of relapse, transplant-related mortality and overall survival were 21.0 ± 10.8% 13.7 ± 10.8% and 66.0 ± 12.4%, respectively. Ten (66.7%) of 15 patients are alive with complete molecular remission, even after a median follow-up of 25 months after withdrawal of imatinib. In conclusion, even CML in advanced phases may have a satisfactory outcome after myeloablative allo-HSCT combined with imatinib, which may provide good remission prior to transplantation and reduce relapse risk, with low toxicity.     

OMISSION OF DAY ＋11 METHOTREXATE DOES NOT APPEAR TO INFLUENCE INCIDENCE AND SEVERITY OF GRAFT-VERSUSHOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Objective: To explore the influence of omission of the day 11 dose of methotrexate (MIX) on the incidence and severity of graft-versus-host disease(GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: From April 1997 to October 2002, 80 leukemia patients (46 men and 34 women aged from 12 to 56 years with a median age of 35) underwent allo-HSCT at our BMT unit. Among them, 58 patients received grafts from HLA-identical siblings, 8 from HLA one major antigen mismatched siblings and 14 from HLA-matched unrelated donors.All patients received a modified cyclosporine and short-course MTX regimen for GVHD prophylaxis,which included MTX 15 mg on day 1, and 10 mg on days 3 and 6 (MTX day 11 dose omitted) and cyclosporine given daily. Results: The overall incidence of grade Ⅰ-Ⅳ acute GVHD was 57.5% (46/80 patients), with grade Ⅱ-Ⅳ acute GVHD in 28 patients(35%) and grade Ⅲ-Ⅳ acute GVHD in 7 patients(8.8%). Among 58 patients receiving grafts from HLA-identical siblings, 24 patients developed grade Ⅰ-Ⅳ acute GVHD (41.4%), with grade Ⅱ-Ⅳ acute GVHD in 13 patients (22.4%) and grade Ⅲ-Ⅳ acute GVHD in 4 patients (6.9%). 21 out of 22 patients receiving grafts from HLA one major antigen mismatched siblings and HLA-matched unrelated donors developed grade Ⅰ-Ⅳ acute GVHD (95.5%),with grade Ⅱ-Ⅳ acute GVHD in 14 patients (63.6%)and grade Ⅲ-Ⅳ acute GVHD in 3 patients (13.6%).Chronic GVHD occurred in 38 out of 56 evaluable patients (67.9%), with extensive form in 15 patients(26.8%) and limited form in 23 patients (41.1%). With a median follow-up of 960 days (range 180-1980 days), the probability of leukemia-free survival at 3 years was 61.3% for all patients. Conclusion: Our results suggest that the day 11 MTX can be omitted without a major deleterious effect on the incidence and severity of graft-versus-host disease after HLA-identical sibling transplantation as well as HLA one major antigen mismatched sibling and HLA-matched unrelated donor transplantation.     

含氟达拉滨的预处理行异基因造血干细胞移植治疗恶性血液病的远期疗效

目的:观察含氟达拉滨的预处理方案进行异基因造血干细胞移植治疗恶性血液病的长期疗效。方法:选取2003年2 月至2004年12月间厦门大学附属中山医院收治的15例恶性血液病患者,其中急性髓性白血病3 例,急性淋巴细胞白血病5 例,慢性粒细胞白血病6 例,骨髓增生异常综合症（RAEB）1 例。供受者HLA 配型同胞全相合6 例,同胞或亲缘不相合8 例,非亲缘全相合1 例。预处理方案采用氟达拉滨（Flu 30mg/m2·d,共5d）、马利兰（BU4mg/kg·d,共2～3d）、环磷酰胺（CTX 50mg/kg·d,共2d）,其中8 例加用阿糖胞苷（Ara-c 1.0～2.0g/m2·d,共2d）,9 例HLA 不全相合及非血缘移植者加用兔抗胸腺细胞球蛋白（ATG 3.0～5.0mg/kg·d,共3d）。 预防移植物抗宿主病（GVHD）均采用骁悉（MMF）+ 环孢素（CsA）+ 短程甲氨喋呤（MTX）方案。利用SPSS11.5 统计软件及Kaplan-Meier 方法进行生存分析。结果:15例患者移植后均获得快速完全的植入,无严重的预处理相关毒性。46.7% 发生急性GVHD ,85.7% 发生慢性GVHD ;带状疱疹7.1% 。5 年总生存率为53.5% ,其中移植时处于第一次完全缓解（CR1）和慢性期患者11例,5 年生存率为72.7% ,复发率9.1% ,移植时处于第二次完全缓解（CR2）、复发、加速期及急变期的患者4 例,2 年生存率为0,复发率75,两者有统计学差异（P=0.000 3 和P<0.05）,主要死亡原因为疾病复发和GVHD 。结论:对于移植时处于CR1 和慢性期患者,采用含Flu并适当减低放化疗剂量的预处理方案是有效的移植预处理方案,毒副作用较少,未增加机会性感染,复发率较低;预处理中加入Flu对GVHD 发生率无明显影响。      

白消安联合氟达拉滨低毒预处理异基因造血干细胞移植治疗恶性血液病13例

 【摘要】　目的　探讨经白消安+氟达拉滨（Bu+Flu）方案低毒清髓预处理异基因造血干细胞移植（allo-HSCT）治疗恶性血液病的临床疗效。方法　对13例接受Bu+Flu方案预处理造血干细胞移植白血病患者的临床资料进行回顾性分析。预处理方案为Bu+Flu,同胞不全相合和非血缘移植患者加用兔抗人胸腺细胞免疫球蛋白（ATG）。用环孢素A+短疗程甲氨蝶呤或环孢素A+吗替麦考酚酯预防移植物抗宿主病（GVHD）。采用DNA短串联重复序列（STR）多态性分析方法鉴定供者干细胞植入情况。结果　13例患者均能耐受Bu+Flu预处理方案,未发生严重的预处理相关并发症。中性粒细胞植活中位时间11 d（9~15 d）,血小板植活中位时间13 d（8~25 d）。10例患者造血重建,检测其外周血白细胞STR-DNA证实均为100 %完全供者植入。出现急性GVHD 5例（38.5 %）,可评估的10例患者中,出现慢性GVHD 4例（40.0 %）;无Ⅱ度以上重型GVHD。中位随访11个月（1~39个月）,总生存率为76.9 %（10／13）,无病生存率为61.5%（8／13）。死亡病例原因均为疾病复发。结论　Bu+Flu方案低毒清髓预处理可减轻移植相关并发症,患者有很好耐受性和较好疗效。     

单倍型异基因造血干细胞移植治疗儿童复发难治性急性淋巴细胞白血病的临床研究

目的 探讨单倍型异基因造血干细胞移植(allo-HSCT)治疗儿童复发难治性急性淋巴细胞白血病(ALL)的疗效和安全性.方法 选择北京军区总医院血液科2010年1月至2013年1月采用allo-HSCT治疗的儿童复发难治性ALL患者20例,其中男12例,女8例,中位年龄9岁(1～ 14岁);B-ALL 14例,T-ALL 6例;移植时复发未缓解10例,复发后取得2次或者3次缓解10例;6例采用骨髓加外周血干细胞联合移植,14例仅采用外周血干细胞移植;预处理方案主要为白消安、氟达拉滨、环磷酰胺、抗胸腺细胞免疫球蛋白,部分患儿加用阿糖胞苷、依托泊苷或司莫司汀及接受全身照射等.移植物抗宿主病(GVHD)的预防采用环孢素、吗替麦考酚酯、甲氨蝶呤(+1、+3、+6、+11天).移植后观察患儿不良反应、并发症和无病生存等情况.结果 全部患儿均获重建造血,移植后1个月供者细胞嵌合率均为100％.移植后粒细胞植活中位时间为12.5d(9～23d),血小板植活中位时间为15d(12～40d).随访至2014年6月,中位随访时间25个月(2 ～ 50个月),8例发生急性GVHD,11例发生慢性GVHD,因GVHD死亡2例,感染死亡1例,复发死亡2例,共死亡5例,其余15例患儿生存,全组患者的总体生存率为75％.结论 单倍型allo-HSCT治疗儿童复发难治性ALL安全可行,长期生存率提高,移植后并发症及复发率并未增加.     

急性髓系白血病患者异基因骨髓移植后复发行同一供者二次移植一例

 目的　探索血缘HLA全相合骨髓造血干细胞移植（HSCT）后复发病例进行同一供者外周血造血干细胞二次移植（HSCT2）的可行性。方法　1例急性髓系白血病（M4）患者接受血缘HLA全相合供者骨髓移植后18个月复发,染色体检查提示为受者复发型。给予CY-TBI预处理后输注同一供者外周血HSCT2,同时降低预防移植物抗宿主病（GVHD）强度。结果　患者HSCT2后获得稳定植入,患者并发急性GVHD（肠道Ⅳ级,皮肤Ⅲ级）,完全缓解至+8月。结论　对于血缘造血干细胞供者移植后复发的患者,HSCT2同一供者HSCT是可行的。     

Problems and strategies for bone marrow transplantation in acute leukemia and chronic myelogenous leukemia

Certain marrow transplant protocols can now result in a 50-70% long disease-free survival and low relapse rates in acute leukemia (AL) in CR1, CR2, or CML following cytoreduction and HLA-identical marrow infusion. Two-thirds of deaths are due to acute and chronic graft-versus-host disease (GVHD) or viral infection. The other deaths are due to toxicities of the cytoreductive treatment. Prevention of GVHD has been tried by treatment after the transplant or treating the marrow (lymphocyte depletion). Cyclosporine (CsA) or CsA plus methotrexate has reduced acute GVHD but not chronic GVHD. Marrow has been treated with monoclonal antibodies and lectins or elutriated to decrease numbers of T lymphocytes. Some studies have been effective, but the majority have shown an increased number of rejections or leukemic relapses. Apart from teratogenic effects, thalidomide has minimal toxicity. It effectively prevents and treats acute and chronic GVHD in rodent models. Clinical trials will soon begin. Mismatched related or matched unrelated donors have been employed in the clinic with limited success. Alternatively, autologous transplantation in acute leukemia has shown promising results. Possible solutions to remaining problems and strategies will be discussed.     

伊马替尼联合造血干细胞移植治疗慢性粒细胞白血病

 目的 研究伊马替尼（商品名：格列卫）对异基因造血干细胞移植（allo-HSCT）和自体外周血造血干细胞移植（APBSCT）的影响。方法 18例慢性粒细胞白血病（CML）分为2组：①al-lo-HSCT组14例,其中10例为CML加速期（AP）和急变期（BP）,4例为CML慢性期（CP）,移植之前格列卫疗程中位数为25（7～60）d,供受者HLA完全相合,亲缘相关供者9例、非亲缘供者5例,预处理方案为TBI+Cy+VP16或Bu／Cy±ATG,GVHD预防按常规方案进行;②APBSC动员4例,均为CML-CP患者,格列卫治疗的中位数疗程5.5（4～26）个月,动员前反复IFISH-bcr／abl阳性率0～2%,动员方案CAE+G-CSF,其中3例经TBI+Cy+VP16预处理后进行了APBSCT。结果 4例患者经G-CSF动员第5天分离自体外周血干细胞（APBSC）1次,得CD+34细胞的中位数6.8（3.9～9.6）×106／kg,动员产品中IFISH-bcr／abl阳性细胞比例高于动员前骨髓细胞（2.8 %∶0.8 %）,4例动员PBSC的患者中3例进行了APBSCT,移植后随访中位时间24（18～28）个月,2例复发,1例持续IFISH-bcr／abl阴性。14例allo-HSCT患者中位随访8（4～20）个月,造血重建需要8～21 d,发生GVHD 8例,白血病复发2例,移植相关并发症死亡2例,复发死亡1例,无病生存9例。结论 格列卫治疗后对CML患者造血干细胞的动员、移植结果无明显影响。     

HLA相合同胞供者异基因造血干细胞移植治疗慢性粒细胞白血病的疗效及预后因素分析

目的探讨HLA相合同胞供者异基因造血干细胞移植（allo-HSCT）治疗慢性粒细胞白血病（CML）的疗效及预后因素。方法35例CML患者,11例行HIA相合同胞供者异基因骨髓移植（allo-BMT）,24例行异基因外周血干细胞移植（allo-PBSCT）。全身照射（TBI）＋环磷酰胺（CY）方案预处理8例,白消安（BU）＋CY方案预处理27例。结果造血重建34例（97．1％）,3年无病生存率（DFS）为60．0％,5年累积生存率为57．1％。复发2例,移植相关死亡12例。并发症包括出血性膀胱炎（HC）5例,肝静脉闭塞病（HVOD）1例,急性移植物抗宿主病（GVHD）18例,慢性GVHD 17例。单因素分析显示,年龄≤30岁、慢性期移植、Ⅰ和Ⅱ度急性GVHD患者3年DFS分别高于年龄〉30岁、加速期移植及Ⅲ和Ⅳ度急性GVHD患者。多因素Cox回归分析结果表明,年龄、疾病状态、急性GVHD的严重程度是allo-HSCT患者长期生存的独立影响因素。结论年龄≤30岁、慢性期、轻度GVHD的CML患者行allo-HSCT治疗,可获得较高的长期生存率。     

造血干细胞移植治疗淋巴瘤:第56届美国血液学会年会报道

第56届美国血液学会年会关于造血干细胞移植(HSCT)治疗淋巴瘤的摘要171篇,其中自体HSCT(auto-HSCT) 102篇、异基因HSCT(allo-HSCT) 69篇.会议主要讨论了HSCT治疗复发难治霍奇金淋巴瘤及高危、侵袭性非霍奇金淋巴瘤的疗效及其影响疗效的因素,包括移植时机、预处理方案、靶向化疗药物应用、allo-HSCT后移植物抗宿主病预防及移植后临床预测指标等众多方面.     

Improvement over time in outcome for children with acute lymphoblastic leukemia in second remission given hematopoietic stem cell transplantation from unrelated donors.

Aims of this study were to verify whether reduction in transplant-related mortality (TRM) of children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) given allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated volunteers has occurred over time and to investigate the role of other variables on the probabilities of relapse, TRM and event-free survival (EFS). We compared results obtained in 26 children given HSCT before January 1998 with those of 37 patients transplanted beyond that date. In all donor-recipient pairs, histocompatibility was determined by serology for HLA-A and -B antigens and by high-resolution DNA typing for DRB1 antigen. High-resolution molecular typing of HLA class I antigens was employed in 20 of the 37 children transplanted more recently. Probability of both acute and chronic GVHD was comparable in the two groups of patients. In multivariate analysis, children transplanted before January 1998, those with T-lineage ALL and those experiencing grade II-IV acute GVHD had a higher relative risk of TRM at 6 months after transplantation. Relapse rate was unfavorably affected by a time interval between diagnosis and relapse <30 months. The 2-year probability of EFS for children transplanted before and after 1 January 1998 was 27% (10-44) and 58% (42-75), respectively (P = 0.02), this difference remaining significant in multivariate analysis. EFS of unrelated donor HSCT in children with ALL in second CR has improved in the last few years, mainly due to a decreased TRM. This information is of value for counseling of patients with relapsed ALL.     

Relapse of chronic myelogenous leukemia 12 years after allogeneic marrow transplantation: successful second transplantation with allogeneic peripheral blood progenitor cells.

We report on a 31-year old female patient who relapsed with CML in blast crisis 12 years after a successful BMT for CML in chronic phase from her HLA-identical sister. Because of her good performance status and the long time elapsed since her first BMT, PBPC transplantation of the originial donor was planned. Therefore, the patient was conditioned with busulfan and cyclophosphamide and then received unmanipulated PBPCs from her sister. GVHD prophylaxis consisted of MTX and CsA. She had early engraftment but considerable hepatotoxicity which resolved after more than six months. Furthermore, she developed acute GVHD of the skin grade 2, which responded to corticosteroids. Fifteen months after second transplantation the patient is alive and well in molecular remission and without signs of chronic GVHD.     

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.     

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.     

异基因造血干细胞移植患者72例急性移植物抗宿主病临床研究

 目的　探讨异基因造血干细胞移植（allo-HSCT）后急性移植物抗宿主病（aGVHD）的发生及其危险因素。方法　总结2004年10月至2008年12月治疗的72例allo-HSCT患者的临床资料。回顾性分析患者各临床因素与aGVHD发生的关系。结果　32例患者发生Ⅰ～Ⅳ度aGVHD,累积发生率44.4 %。其中Ⅰ度8例（11.1 %）,Ⅱ度13例（18.1 %）,Ⅲ度7例（9.7 %）,Ⅳ度4例（5.6 %）。单因素分析显示疾病种类（P＜0.1）、抗人类T淋巴细胞球蛋白（ATG）的应用（P＜0.1）、疾病状态（P＜0.1）、预处理方案（P＜0.1）、供者类型（P＜0.1）、 供受者血型不合（P＜0.1）、回输CD+34 细胞数量（P＜0.1）、移植早期感染以及HLA配型均与aGVHD的发生有关。多因素分析（Cox regression）确定不含ATG的GVHD预防方案（HR＝2.94,P＜0.001）、HLA配型不合（HR＝2.58,P＜0.005）以及无关供者 （HR＝1.97,P＜0.01）是发生aGVHD的主要危险因素。结论　aGVHD是allo-HSCT的重要并发症,HLA配型不合以及无关供者是aGVHD发生的主要危险因素。     

异基因造血干细胞移植治疗难治性急性白血病

目的:观察异基因造血干细胞移植(Allo蛳HSCT)对未缓解期白血病患者的疗效。方法:4例难治性白血病,其中3例耐药复发,1例继发性白血病,经常规化疗2 个~10 个疗程未能达到缓解。供、受者HLA配型不全相合1例,其余3例完全相合。预处理方案:Bu/Mal1例,Bu/Cy3例(其中2例ALL加用ACNU)。GVHD预防:CsA+短程MTX,2例加用MMF,1例HLA不全相合者加用ATG和MMF。输入的单个核细胞数(8.05~13.65)×108/kg。结果:4例造血细胞均成功植入,ANC>0.5×109/L的中位时间为12 d,血小板>50×109/L的中位时间为22.5 d;基因型完全转换成供者型的中位时间为15 d;3例供、受者红细胞血型不合者分别于35 d、38 d、26 d转变成供者血型。4例移植后均获CR,骨髓象完全缓解的中位时间为20.5 d。除1例因GVHD死亡外,其余3例迄今均无白血病生存。结论:Allo蛳HSCT对于难治性白血病是有效的治疗选择。     

造血干细胞移植治疗骨髓增生异常综合征的研究进展

 人类白细胞抗原（HLA）匹配同胞供者造血干细胞移植是治疗骨髓增生异常综合征（MDS）最有效的方法,其疗效在过去十几年里有明显的提高。在缺乏同胞供者来源时,无关供者移植、脐带血移植、自体造血干细胞移植可以作为替代的治疗选择。现对MDS患者移植适应证、影响移植疗效的因素（包括年龄、移植时机、移植前诱导缓解化疗、预处理方案、造血干细胞来源等）进行综述。     

异基因外周血造血干细胞移植联合骨髓移植治疗白血病30例

 目的　观察异基因外周血干细胞移植联合骨髓移植对白血病的疗效。方法　白血病患者30例,平均年龄32.6岁,其中急性髓细胞白血病（AML） 11例,急性淋巴细胞白血病（ALL） 14例,慢性粒细胞白血病（CML）5例,供者均为HLA相合同胞,动员方案为每天G-CSF 5 μg／kg,共5 d,并于外周血干细胞回输当天采集供者骨髓300 ml回输;预处理方案采用Bu／Cy,移植物抗宿主病（GVHD）预防采用环孢素A（CsA）联合甲氨蝶呤（MTX）、吗替麦考酚酯（MMF）。结果　回输外周血单个核细胞（5.13±2.6）×108／kg,骨髓单个核细胞（1.3±0.6）×108／kg,30例患者均成功植活,其中中性粒细胞＞0.5×109／L的时间为（12.1±3.25）d,血小板＞0.5×109／L的时间为（14.0±5.33）d;Ⅰ～Ⅱ度aGVHD发生率为40.0 %（12／30）,Ⅲ～Ⅳ度发生率3.3 %（1／30）,cGVHD发生率为43.3 %（13／30）,严重cGVHD发生率为3.3 %（1／30）;2年无病生存率达72.0 %。结论　异基因外周血造血干细胞移植联合骨髓移植是治疗白血病的有效方法,并有可能减少重度急、慢性GVHD的发生。