异基因造血干细胞移植治疗急性髓系白血病的临床分析

目的 探讨异基因造血干细胞移植(allo-HSCT)对急性髓系白血病(AML)的治疗效果,分析可能影响预后的相关因素。方法 回顾性分析47例AML患者的临床资料,所有患者均行allo-HSCT治疗。应用Kaplan-Meier生存曲线评定患者的总生存率(OS),采用Log-rank检验行不同组别的比较,应用Cox回归法探究影响预后的有关因素。结果47例患者中存活32例,死亡15例,7例复发;5年OS为(61.23±6.75)%,中位生存时间77.6个月,5年复发率为(15.83±4.26)%;Log-rank检验结果表明前后期各不相同的移植方案、缓解次数、移植前缓解情况、各不相同的供者来源、是否合并移植物宿主病(GVHD)与OS无关(P>0.05);多因素分析表明,合并髓系肉瘤和复发为患者预后的主要影响因素(P<0.05)。结论 allo-HSCT在AML患者治疗中效果确切,随着移植手段的转变与支持治疗的进步,患者的生存周期逐渐延长,而合并髓系肉瘤和复发是造成不良预后的有关因素,临床需予以积极的重视。     

异基因造血干细胞移植治疗急性髓系白血病的现状

 异基因造血干细胞移植（allo-HSCT）是治疗急性髓系白血病（AML）的有效方法之一。allo-HSCT的治疗作用来自于预处理中的放疗和（或）化疗,以及供者免疫系统的移植物抗白血病（GVL）效应。近十年来,随着对白血病细胞生物学特性研究的不断深入,根据细胞遗传学和分子标志对AML进行危险程度分级,使我们能够挑选出哪些AML患者可以从allo-HSCT中获益。allo-HSCT治疗AML的临床疗效已有明显提高,并且适用范围也较前扩大,但在AML中的应用还存在一定差异。现对allo-HSCT治疗AML的机制、时机、疗效、供者选择及预处理方案进行讨论。     

异基因外周血干细胞移植治疗慢性髓系白血病17例

目的 :探讨异基因外周血干细胞移植治疗慢性髓系白血病(CML)的临床疗效及移植并发症的情况。 方法 :对17例CML患者进行异基因外周血干细胞移植,其中慢性期15例,加速期、急变期各1例。供者均为同胞兄妹,16例为HLA全相合,1例为2个位点不合。预处理方案采用BU/CY方案,应用CsA、MMF和短程MTX预防GVHD。 结果 :全部患者造血功能均获得快速重建,中性粒细胞绝对值≥0.5×10⁹/L的平均时间为移植后+11(+9～+13)天,血小板≥20×10⁹/L的平均时间为移植后+16(+14～+21)天。16例HLA全相合移植中发生急性Ⅰ度GVHD1例(6.25%),慢性GVHD4例(25.00%);1例HLA2个位点不合移植患者发生急性Ⅱ度GVHD。中位随访时间19个月(2～43个月),15例CP期患者均无病生存,2例AP期及BP期患者分别于移植后9个月及6个月死亡。 结论 :Allo-PBSCT是治疗CML的有效方法,CsA/MMF/MTX三联方案可以有效地预防急性GVHD。     

造血干细胞移植治疗急性髓系白血病42例

目的 评价造血干细胞移植（HSCT）治疗急性髓系白血病（AML）的临床疗效.方法 收集2007年1月至2013年7月在我科行HSCT的AML 42例,其中自体造血干细胞移植（auto-HSCT）16例,异基因造血干细胞移植（allo-HSCT） 26例（含单倍体移植6例）,回顾性分析患者的临床资料.结果 39例患者获得造血重建,中性粒细胞绝对值＞0.5×109/L、血小板计数＞20×109/L的中位时间分别为11.0 d、13.5 d.发生急性移植物抗宿主病（aGVHD）3例,慢性移植物抗宿主病（cGVHD）7例,真菌感染4例,出血性膀胱炎7例.9例复发,24例无病生存（DFS）,总生存（OS）率59.5％,DFS率57.1％.自体移植组与异基因移植组疗效差异无统计学意义（P＞0.05）.结论 allo-HSCT是AML的有效治疗手段,随着移植技术的进步,在没有HLA相合供者时,auto-HSCT、单倍体移植也值得推荐.     

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。     

异基因干细胞移植后急性髓系白血病复发的治疗进展

急性髓系白血病(AML)是一种表型和预后异质性造血干细胞疾病,在接受强化化疗和/或异基因造血干细胞移植(allo-HSCT)的患者中可能得到治愈.随着测序技术的发展揭示了大量分子信息,显著改善了我们对AML基础病理生理学的理解并促进了靶向疗法的发展,目前正在研究几种靶向分子改变的小分子,如FLT3抑制剂、异柠檬酸脱氢酶...     

STI571在慢性髓细胞白血病急变期造血干细胞移植治疗中的作用

目的：探讨STI571在慢性髓细胞白血病(CML)急变期外周血干细胞移植中的应用价值。方法：CML急变期患者接受STI571治疗,然后进行异基因造血干细胞移植,同时进行临床观察。结果：3例CML急变期患者均获得临床血液学缓解,STI571对异基因造血干细胞移植后的造血恢复无影响。结论：STI571对CML急变期有治疗作用,可应用于造血干细胞移植前治疗,二者结合有可能使患者生存期延长。     

Hematopoietic Stem Cell Transplantation for Patients with Chronic Myeloid Leukemia

OBJECTIVE To evaluate the effects of autologous and allogeneic hematopoietic stem cell transplantation (HSCT) for patients with chronic myeloid leukemia(CML).METHODS Fifty-seven patients with CML were treated by HSCT, including 8 cases treated with autologous transplantation purged in vivo and in vitro of minimal residual disease (MRD), 39 cases with related donor allogeneic HSCT (allo-HSCT) and 10 cases with unrelated donor alIo-HSCT. The conditioning regimen was a TBI (total-body irradiation) CY (cyclophosphamide, CTX) protocol in 32 patients, a modified BuCY (hydroxyurea, busulfan, Ara-C, CTX) protocal in 24 patients, and a MACC ( Melphalan, Ara-C, CTX and chlorethyl cyclohexyl nitrosourea ) protocol in one patient. Cyclosporine (CsA) and methotrexate (MTX) were used in patients with related-donor allo-HSCT, and CsA and MTX were added to mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) in unrelated donor allo-HSCT for graft versus host disease (GVHD) prophylaxis. Otherwise, CsA was only used for GVHD prophylaxis in patients with accelerated phase (AP) and blast crisis (BC). The Kaplan-Meier survival analysis model was used to estimate the overall survival (OS) and the disease-free survival (DSF) at 5 years after transplantation.RESULTS Eight patients with autologous transplantation, except for 1 case who died of transplantation-related complications, obtained cytogenetic part or complete remission (CR) within 3 months after transplantation. One patient, who was in BC and obtained CR in hematology before transplantation, had been in molecular CR for 92 months after autologous transplantation. Among the 49 patients treated with alIo-HSCT, all obtained CR, except for one patient who died of hepatic veno-occlusive disease (VOD) and one who had not obtained CR. The incidence of infection and VOD was 33.3% and 7.0%, respectively, during transplantation. After transplantation the incidence of hemorrhagic cystitis (HC) and cytomegalovirus (CMV) interstitial pneumonia (IP) was 22.8% and 8.8%, respectively. VOD, HC and CMV IP did not occur in patients with autologous transplantation. The incidence of acute GVHD and the frequency of chronic GVHD was 41.0% and 48.6%, respectively, in patients with related and unrelated transplantation. The rate of relapse in patients with autologous and allogeneic transplantation was 57.1% and 12.8%, respectively. The DFS at 5 years after transplantation was 25.0% and 61.7%, respectively, in patients with autologous and related donor transplantation. The DFS at 5 years was 70.7% and 34.1%, respectively, in patients with CP (chronic phase) or AP and BC before transplantation.CONCLUSION AIIo-HSCT may have a higher clinical cure rate for CML patients with CP. The CsA MTX MMF ATG protocol is more effective for acute GVHD prophylaxis and can decrease the incidence and degree of GVHD in patients with unrelated donor transplantation, Autologous transplantation with purged bone marrow can prolong the survival time of CML patients and some may be cured with transplants of this type.     

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。     

急性髓系白血病合并慢性淋巴细胞白血病一例报道及文献复习

 目的 探讨急性髓系白血病（AML）合并慢性淋巴细胞白血病（CLL）的临床特点、病因、诊断、治疗及预后。方法 临床诊断1例AML合并CLL,并就相关文献进行复习。结果 患者经MA方案（米托蒽醌10 mg／d第1 ~ 3天,阿糖胞苷150 mg／d第1,3,5,7天,200 mg第2,4,6天）化疗后取得完全缓解,但CD19阳性的淋巴细胞（表达CD20,CD23,SIgM,部分表达CD5,CD22,CD25）仍然存在,于9个月后AML复发未能再次缓解而死亡。结论 AML合并CLL为一种具有特殊生物学特征的罕见疾病,免疫分型和细胞遗传学技术在疾病的诊断和认识中发挥重要作用,治疗应以AML为主。     

急性髓性白血病混合造血干细胞移植后DLI＋IL-2治疗的临床研究

目的：探讨急性髓性白血病（acute myeloid leukemia,AML）患者在接受自体外周血干细胞混合人类白细胞抗原（human leukocyte antigen,HLA）半相合异体骨髓移植（Mixed-HSCT）后,继予供体淋巴细胞输注＋白介素2（DLI＋IL-2）治疗的疗效。方法：对23例AML患者在完全缓解期采用TBI＋VEMAC预处理方案,实施Mixed-HSCT。造血恢复后给予DLI＋IL-2治疗1-8次。结果：所有患者均获得造血重建,中性粒细胞（ANC）≧0.5×109/L的中位时间为14（12-17）天,白细胞（WBC）≧4.0×108/L的中位时间为17（16-21）天。血小板（PLT）≧20×108/L的中位时间为21（19-23）天,PLT≧50×108/L的中位时间为25（24-27）天。＋16至＋21天时骨髓检查示恢复期骨髓象,无移植物抗宿主病（graft versus host disease,GVHD）发生,有6例形成混合嵌合体（46XX/46XY）。经过3年以上随访,存活15例,长期无病存活率（DFS）为65.2%。结论：Mixed-HSCT后应用DLI＋IL-2治疗对急性髓性白血病患者的长期无病生存有积极意义。     

急性髓性白血病混合造血干细胞移植后DLI+IL-2治疗的临床研究

目的:探讨急性髓性白血病(acute myeloid leukemia,AML)患者在接受自体外周血干细胞混合人类白细胞抗原(human leukocyte antigen,HLA)半相合异体骨髓移植(Mixed-HSCT)后,继予供体淋巴细胞输注+白介素2(DLI+IL-2)治疗的疗效。方法:对23例AML患者在完全缓解期采用TBI+VEMAC预处理方案,实施Mixed-HSCT。造血恢复后给予DLI+IL-2治疗1-8次。结果:所有患者均获得造血重建,中性粒细胞(ANC)≧0.5×109/L的中位时间为14(12-17)天,白细胞(WBC)≧4.0×108/L的中位时间为17(16-21)天。血小板(PLT)≧20×108/L的中位时间为21(19-23)天,PLT≧50×108/L的中位时间为25(24-27)天。+16至+21天时骨髓检查示恢复期骨髓象,无移植物抗宿主病(graft versus host disease,GVHD)发生,有6例形成混合嵌合体(46XX/46XY)。经过3年以上随访,存活15例,长期无病存活率(DFS)为65.2%。结论:Mixed-HSCT后应用DLI+IL-2治疗对急性髓性白血病患者的长期无病生存有积极意义。     

混合造血干细胞移植联合DLI-IL-2治疗急性髓性白血病的疗效

目的:探讨急性髓性白血病(acute myelogenous leukemia,AML)患者采用自体外周血干细胞混合HLA半相合异体骨髓移植(autologous peripheral blood stem cell mixed with HLA haploidentical allogeneic bone marrow transplantation,Mixed-HSCT)联合供体淋巴细胞输注+白介素2(donor lymphocyte infusion combined interleukin-2,DLI-IL-2)治疗的疗效。方法:采用联合治疗方案的试验组23例AML患者中男性15例、女性8例,中位年龄22(17～41)岁;采用单纯移植治疗的对照组14例AML患者中男性10例、女性4例,中位年龄21(19～40)岁。两组患者在完全缓解期采用TBI+VEMAC方案预处理,对照组患者接受单纯Mixed-HSCT移植,试验组患者接受Mixed-HSCT且造血重建后继续DLI-IL-2治疗1～8次;各组在治疗前后进行染色体核型分析及骨髓检查。随访时间>3年。结果:两组患者均获得造血重建,无移植物抗宿主病(graft-versus-host disease,GVHD)发生。试验组有6例形成混合嵌合体(46XX/46XY),随访显示存活15例,长期无病存活率(disease-free survival,DFS)为65.2%;对照组有3例形成混合嵌合体(46XX/46XY),随访显示存活7例,DFS为50.0%。两组患者治疗后的不良反应(口腔溃疡、出血性膀胱炎、发热等)相似。结论:Mixed-HSCT联合DLI-IL-2治疗对AML患者长期无病生存有积极意义,无严重不良反应。     

Hematopoietic stem cell transplantation in chronic lymphocytic leukemia: A report of 12 patients from a single institution

Background: Stem-cell transplantation is a reasonable therapeutic approach for younger patients with high-risk CLL.Patients and methods: Twelve patients (seven males; median age 47 years, range 29–51) with high-risk CLL underwent transplantation (allo, n = 7; auto, n = 5). The conditioning regimen consisted of cyclophosphamide and total body irradiation in 11 patients, and BEAC in the remaining one. Minimal residual disease (MRD) was assessed by cytofluorometry and PCR.Results: All 11 evaluable patients engrafted. Of the seven allografted patients, two died of treatment-related causes; three patients developed acute GVHD. No transplant-related mortality was observed in autografted patients. After transplantation, 10 of 11 patients evaluable for response achieved CR (91%; 95% CI 59%–100%) which was molecular in nine patients (82%; 95% CI 48%–98%). One patient in CR but MRD+ relapsed nine months after transplantation and died. Seven patients remain in molecular CR for a median of 16 months (range 1–58). Estimated actuarial survival and disease-free survival at two years is 81% (95% CI 43%–100%) and 71% (95% CI 43%–99%), respectively. Relapse risk at two years is 12.5% (95% CI 0%–35.5%).Conclusions: Patients with high-risk CLL can achieve long-lasting molecular CR after SCT. The role of transplants in CLL management deserves investigation in controlled trials.     

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.     

亚砷酸钠治疗加速期慢性粒细胞性白血病的疗效观察

目的:观察亚砷酸钠治疗加速期性粒细胞性白血病(CML)的临床疗效.方法:依据外周血白细胞数,每日静脉滴注亚砷酸钠10～15mg.结果:经过平均40. 5天治疗,7例诊断为加速期慢性粒细胞白血病患者中,3例CR,4例PR,患者对亚砷酸钠均耐受良好,并见到临床与血液学及CFU-GM的明显改善,但无Ph染色体及融合基因改变.结论:亚砷酸钠可通过诱导细胞凋亡而用于CML加速期患者的临床治疗.     

Simultaneous occurrence of a T-cell lymphoma and a chronic myelogenous leukemia with an unusual karyotype

The simultaneous occurrence of malignant T-cell lymphoma and chronic myelogenous leukemia is reported. The lymph nodes contained E rosette forming cells. Blood and bone marrow cell morphology were consistent with the diagnosis of chronic myelogenous leukemia. Lymph nodes, bone marrow and blood mitosis showed a t(6;8) (6pter→6q27 ::8p12→8pter;6qter→6q27 ::8p12→8qter) translocation.So far a number of recent reports have shown simultaneous B lymphoid and myeloid proliferations in some malignancies, this is apparently the first reported case of simultaneous T lymphoid and myeloid proliferations.