非清髓异基因外周血造血干细胞移植治疗慢性粒细胞白血病

目的：探索非清髓异基因外周血干细胞移植(NST)治疗不能耐受清髓性异基因造血干细胞移植的慢性粒细胞白血病(CML)患者的疗效。方法：将5例CML患者中的4例以全身放疗加氟达拉宾，1例以马利兰、氟达拉宾加抗人胸腺细胞免疫球蛋白为预处理方案，联合环孢霉素A、霉酚酸酯和(或)短程氨甲蝶呤预防移植物抗宿主病。结果：5例均造血重建，3例完全供者型植入，2例混合型植入，其中1例植入率持续低于50％，经2次清髓性异基因造血干细胞移植后达到完全供者型植入。2例发生Ⅰ度急性移植物抗宿主病，1例发生Ⅳ度急性移植物抗宿主病，无慢性移植物抗宿主病发生。中位随访时间5(3～37)个月，无病生存3例，死亡2例。结论：对不能耐受清髓性异基因造血干细胞移植的CML患者，NST是可行而有效的。     

非清髓异基因造血干细胞移植治疗慢性粒细胞白血病

目的　探讨非清髓异基因造血干细胞移植 (NST)治疗慢性粒细胞白血病 (CML)的临床效果。方法　对 4例慢性粒细胞白血病患者进行了非清髓异基因造血干细胞移植 ,均采用以氟达拉宾为基础的非清髓预处理方案。回输CD+ 3 4 细胞分别为 9.78× 10 6/Kg、16.5 6× 10 6/Kg、2 .5 6×10 6/Kg和 2 .0 6× 10 6/Kg。结果　 4例均顺利渡过造血抑制期。 4例患者移植后WBC >1.0× 10 9/L ,中性粒细胞 >0 .5× 10 9/L ,时间分别为 +19天、+16天、+13天和 +14天 ;血小板 >2 0× 10 9/L时间分别为 +8天、+12天、+18天和 +2 2天。 2例骨髓细胞混合嵌合体形成 +15～ +2 3天 ,完全嵌合体形成 +2 3～ +4 3天 ;另 2例均于 +17天形成完全嵌合体。 4例均未发生急性移植物抗宿主病 ,例 1于第 5次供者淋巴细胞输注后发生皮肤慢性移植物抗宿主病 ,例 3于第 7次供者淋巴细胞输注后发生慢性移植物抗宿主病。 3例于非清髓异基因造血干细胞移植后 6～ 12个月出现移植物抗白血病。 4例均未发生肝静脉阻塞病、出血性膀胱炎及间质性肺炎。随诊 2～ 2 4个月 ,仍全部存活。结论　非清髓异基因造血干细胞移植治疗慢性粒细胞白血病简便、安全、并发症及支持治疗少、疗效较好。     

格列卫联合异基因造血干细胞移植治疗慢性粒细胞白血病

目的:为了考察格列卫联合异基因造血干细胞移植治疗慢性粒细胞白血病(CML)对移植及造血重建的影响。方法:对6例CML患者于移植前6周开始口服格列卫600~800mg/d至移植当日,预处理方案是福达拉宾、白消安、环磷酰胺,人类白细胞抗原(HLA)不相合者加用抗胸腺细胞球蛋白。移植物抗宿主病防治采用环孢素A加短程甲氨喋呤加霉酚酸酯。结果:6例全部成功植入,WBC>0.5×109·L-1平均为14.2d,PLT>20×109·L-1平均为15.6d。结论:CML患者移植前给予大剂量格列卫治疗不影响干细胞植入和骨髓造血的恢复。     

非清髓性外周血干细胞移植治疗慢性粒细胞性白血病慢性期及加速期的疗效观察

目的:观察非清髓造血干细胞移植对慢性粒细胞白血病慢性期(CMLCP)、加速期(CMLAP)的疗效。方法:用福达华30mg/m2×6d,白消安4mg/kg×2d,环磷酰胺600mg/d×2d,部分患者加阿糖胞苷0.5g,q12h×4次,对12例人类白细胞抗原(HLA)全相合者进行预处理,并对其造血恢复等指标动态观察。结果:12例患者造血顺利恢复,中性粒细胞(ANC)>0.5×109/L平均为13d,血小板计数(PLT)>20×109/L平均为11.5d。+30d时经短串重复系列(STRPCR)检测12例植活患者中9例为完全嵌合状态(CDC),3例为混合嵌合体。+90d时又有1例患者转为CDC。中位随访8(2～20)个月,11例患者无病生存,1例患者死于严重移植性抗宿主疾病。结论:非清髓造血干细胞移植是CMLCP、CMLAP的有效治疗手段,对于年龄较大患者亦有良好耐受性。     

造血干细胞移植治疗慢性髓系白血病的研究进展

慢性髓系白血病 ( CML)是一种获得性多能造血干细胞疾病 ,CML的细胞具有特征性的 Ph染色体及BCR- ABL融合基因。常规治疗虽然可以获得血液学缓解甚至细胞遗传学缓解 ,但不能痊愈。到目前为止 ,同种异基因造血干细胞移植 ( allo- HSCT)仍然是治愈CML的唯一方法 [1]。近年来 ,自体干细胞移植 ( ASCT)也是被积极探索的有效治疗手段之一。　　异基因造血干细胞移植Allo- HSCT移植的平均年龄目前已提高到 4 0岁左右 ,如无重要器质性病变 ,患者年龄可放宽至 55岁。由于感染和移植物抗宿主病 ( GVHD)的防治措施及HLA配型技术的进步 …     

慢性粒细胞性白血病异基因造血干细胞移植的预后及相关因素分析

对43例慢性粒细胞性白血病患者进行异基因外周血造血干细胞移植,将可能影响生存时间的10个变量用逐步回归法,建立COX模型,筛选出相关危险因素。结果CD34细胞计数和慢性移植物抗宿主病（cGVHD）的发生、供体性别的回归系数（参数估计值）均为负值,急性移植物抗宿主病（aGVHD）回归系数（参数估计值）均为正值。提示cGVHD、男性供体、CD34细胞计数为影响慢性粒细胞性白血病异基因造血干细胞移植预后的保护性因素,而aGVHD为危险性因素。     

慢性淋巴细胞白血病的造血干细胞移植治疗

慢性淋巴细胞白血病（CLL）存在很大的临床异质性。尽管免疫化疗方案的进步带来了显著的疗效,部分患者仍可在短期内发生疾病进展,或处于疾病难治耐药的状态。由于移植物抗CLL效应的存在,异基因造血干细胞移植的根治性意义获得肯定。年轻CLL患者如具有高危因素,包括：嘌呤类似物耐药或治疗后早期复发,以及具有17p（TP53位点）缺失和TP53突变,异基因造血干细胞移植是合理的治疗选择。减低强度的预处理方案有效降低了患者的治疗相关死亡率。     

异基因造血干细胞移植治疗慢性粒细胞白血病长生存分析

目的:评价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,并分析影响CML长生存的预后因素。方法:118例CML患者包括慢性期88例、加速期8例、急变期22例,其中83例接受相关移植、35例无关移植。预处理方案:36例患者用全身照射(TBI)联合环磷酰胺联合(Cy)、82例改良BuCy(白消安、环磷酰胺和阿糖胞苷)。移植物抗宿主病(GVHD)预防:68例相关人类白细胞抗原(HLA)全相合移植用环孢素(CsA)和甲氨蝶呤(MTX),50例无关供者及相关1个以上位点不合者采用CsA、MTX、抗胸腺细胞球蛋白(ATG)或麦考酚酸酯(MMF)。Cox模型分析影响长生存的因素。结果:118例患者除3例死于预处理相关毒性(RRT)外其余均获造血重建。移植后5年累计感染发生率为42.6%,巨细胞病毒血症累计阳性率为41.6%。Ⅱ～Ⅳ度急性GVHD累计发生率为33.3%,其中相关全相合供者(MSD)和无关、相关不相合供者(MRD/URD)发生率分别为23.1%和46.9%(P=0.01);1年累计慢性GVHD发生率为47.8%,其中MSD和MRD/URD慢性GVHD发生率分别为51.4%和42.2%(P=0.260)。GVHD致死率为18.3%。移植后5年白血病累计复发率为17%,其中MSD和MRD/URD复发率分别为12.5%和23.9%%(P=0.228)。5年累计总生存(OS)和无病生存(DSF)率分别为69.5%和62.6%,其中MSD与MRD/URD的5年OS率和DSF率分别为78.5%比57.2%和72.7%比48.3%(P=0.018,P=0.017)。慢性期与加速/急变期的5年OS率和DSF率分别79.9%、36.7%和72.4%、32.6%(P<0.001)。多因素Cox模型分析显示,Ⅱ～Ⅳ度急性GVHD、HLA不相合、诊断至移植时间≥1年为OS的独立危险因素。加速期、急变期和三联、四联GVHD预防方案为影响DSF的独立危险因素。结论:影响CML-allo-HSCT长生存的主要因素是移植的时机、疾病状态、HLA相合程度和移植后GVHD。GVHD是移植后死亡的主要原因。     

非清髓性造血干细胞移植治疗白血病的初步临床疗效观察

目的:了解非清髓性造血干细胞移植(NST)的植入和初步临床疗效。方法:NST治疗恶性血液病18例,清髓性外周血干细胞移植(PBSCT)治疗24例。预处理方案:NST组主要包括单用马利兰(Bu)16mg/kg或Bu12mg/kg加阿糖胞苷(Arac)/高三尖杉酯碱(HHT)或一般联合化疗;清髓性PBSCT组包括环磷酰胺(Cy)120mg/kg加单次全身照射(STBI)9～10Gy或Bu16mg/kg/马法兰(Mel)140～160mg/m2加Arac。结果:NST组18例全部重建造血,移植相关死亡3例(16.67%);3年无病生存率(DFS)72.22%±10.56%,中位随访时间为2062(90～2730)d。清髓性PBSCT组造血重建23例,移植相关死亡4例(16.67%);3年DFS70.83%±9.28%,中位随访时间为1936(19～2700)d,两组差异无统计学意义(P>0.05)。NST组外周血象受抑程度明显减轻,WBC最低为0.3(0.2～0.9)×109/L,而清髓性PBSCT组16/24WBC降至0。NST组发生急性移植物抗宿主病(aGVHD)15(83.33%)例、可评估慢性移植物抗宿主病(cGVHD)16例(88.89%),均明显高于清髓性PBSCT组的6例(25%)与cGVHD13例(54.17%)。NST组发热13例(72.22%)而清髓性PBSCT组24例均有发热(100%),感染发生率和持续时间前者明显少于后者(P<0.05)。结论:NST与清髓性PBSCT疗效相当,造血重建快,且其外周血象受抑程度低,治疗安全、有效。     

甲磺酸伊马替尼在慢性粒细胞白血病异基因造血干细胞移植治疗前的应用

目的:动态观察甲磺酸伊马替尼(商品名:格列卫)在2例加速期BCRABL阳性的慢性粒细胞白血病(CML)患者异基因外周血造血干细胞移植(AlloPBSCT)前的应用。方法:应用PCR技术,对接受甲磺酸伊马替尼的BCRABL阳性的CML患者选择不同时间定性检测bcr/abl基因,同时进行骨髓形态学及染色体分析。结果:①甲磺酸伊马替尼治疗1个月后2例均达到血液学完全缓解,病例2达到细胞遗传学完全缓解;②移植后中性粒细胞>0.5×109/L,血小板>20×109/L病例1为13d,病例2为20d;③病例1于+32d血型转为供者型,病例2于+40d供受细胞稳定嵌合,目前2例患者血液学持续完全缓解。结论:化疗可以动员G0期bcr/abl阳性克隆进入增殖周期,表现对甲磺酸伊马替尼敏感,在CML尤其是进入加速期、急变期的患者行PBSCT前应用甲磺酸伊马替尼,有助于体内的bcr/abl白血病细胞清除,达到肿瘤净化作用。     

Treatment of T-prolymphocytic leukemia with nonmyeloablative allogeneic stem cell transplantation

AIM: T-prolymphocytic leukemia (T-PLL) is a rare disease of the elderly characterized by a high white blood cell count and organomegaly, and is currently incurable. Our aim was to elicit graft-versus-leukemia reactions in a patient with T-PLL. METHODS: A 52-yr-old woman with refractory T-PLL underwent a nonmyeloablative regimen followed by allogeneic peripheral blood stem cell transplantation (a "minitransplant") from her HLA-matched sibling. RESULTS: There was no treatment related toxicity other than neutropenia. Engraftment was successful. The patient experienced no graft-versus-host disease (GVHD) at any time but, on day 84 after transplantation, had a relapse in the central nervous system. Despite infusion of donor lymphocytes and intralumbar chemotherapy, she died on day 157 of systemic disease. CONCLUSION: The reasons why treatment may have failed are discussed (nature of disease, disease progression, treatment schedule).     

Long-term follow-up of allogeneic bone marrow transplantation after reduced-intensity conditioning in patients with chronic myelogenous leukemia in the chronic phase

Although allogeneic transplantation is a curative therapy for chronic myelogenous leukemia (CML), treatment-related mortality is still a major cause of death after transplantation, especially in older patients. We investigated the safety and efficacy of reduced-intensity conditioning consisting of low-dose (600 cGy) total body irradiation and cytosine arabinoside (1 g/m2) together with a continuous infusion of granulocyte colony-stimulating factor and cyclophosphamide (120 mg/kg) in patients with CML in the chronic phase. Fractionated splenic irradiation (5 Gy) was also administered as part of the conditioning treatment. Eight patients older than 40 years underwent allogeneic bone marrow transplantation from an HLA-matched sibling following this conditioning. Regimen-related toxicities (equal to or greater than grade III) were not observed. Rapid restoration of 100% donor chimerism was confirmed by fluorescence in situ hybridization methods in 5 sex-mismatched transplant recipients. One patient died from severe acute graft-versus-host disease and another from Pneumocystis carinii pneumonia early in the course of transplantation. A sustained engraftment was achieved in 5 long-term survivors; in 1 case, the graft was rejected but the Philadelphia chromosome and BCR/ABL-negative autologous hemopoiesis were restored. After a minimum follow-up period of 60 months, 6 patients, including the patient with restored autologous hemopoiesis, were still alive and in remission with 100% donor chimerism. Six years after the transplantation, 1 patient experienced a cytogenetic relapse, which was successfully treated with donor lymphocyte infusions. In summary, this reduced-intensity conditioning resulted in a cure with markedly reduced regimen-related toxicities in this relatively older cohort of patients with CML.     

Clonal expansion after bone marrow transplantation in a patient with chronic myelogenous leukemia

Summary A patient with chronic myelogenous leukemia (CML) having the standard [t(9; 22), Ph] translocation is presented where the Philadelphia (Ph) chromosome disappeared following bone marrow transplantation (BMT). The Ph chromosome reappeared in host cells after one year of stable hematologic remission. Three additional cell lines, all possessing the Ph chromosome with other abnormalities were consistently present in her marrow cells. Two years after BMT, ninety percent of her dividing bone marrow cells had become leukemic. The patient's clinical status remains unchanged, despite complex cytogenetic findings. The high incidence of multiple aberrant leukemic clones present in this case remains intriguing. Possible mechanisms for this unique transformation after BMT are discussed.     

Prognostic factors for outcomes of allogeneic stem cell transplantation in chronic phase chronic myeloid leukemia in the era of tyrosine kinase inhibitors

The aim of this study was to estimate the prognostic factors for the outcomes of chronic myeloid leukemia (CML) patients receiving allogeneic stem cell transplantation (SCT) in chronic phase (CP) in the era of tyrosine kinase inhibitors (TKIs). Ninety-seven patients who underwent allogeneic SCT in CP were analyzed. Forty-seven were TKI-naïve at the time of transplant, and 50 received TKI(s) treatment before transplantation. After a median follow-up of 115.8 months, the 4-year overall survival and event-free survival were 80.4 and 58.8%, respectively. Multivariate analysis showed that there were no differences in survival outcomes based on prior TKI therapy. Older age was a prognostic factor for higher treatment-related mortality (TRM), and the type of graft source and younger age were associated with relapse, but prior TKI therapy and disease status at the time of transplant were not associated with either TRM or relapse. Additionally, a major molecular response at 1 month and an MR^4.5 at 3 months were important predictors of favorable long-term outcomes. This study demonstrates the prognostic factors for the outcomes of allogeneic SCT in CP CML and shows that survival outcomes were not affected by the administration of long-term multi-TKI treatment prior to transplantation.     

亲缘异基因造血干细胞移植与STI571治疗慢性粒细胞白血病的临床对比研究

目的：评价对比亲缘异基因造血干细胞移植与酪氨酸激酶抑制剂STI571治疗慢性粒细胞白血病的有效性及安全性。方法：90例慢性粒细胞白血病慢性期患者，分为2组，其中亲缘异基因造血干细胞移植组23例，均采用经典或改良BuCy2方案预处理，短程甲氨蝶呤联合环孢素A（MTX＋CsA）方案预防移植物抗宿主病（GVHD）。STI571组67例，每天应用STI571 400mg，每周复查血常规，每3个月进行骨髓象及细胞遗传学检查，根据血象和骨髓象调整剂量。结果：观察截止时，移植组和STI571组获得细胞遗传学完全缓解率分别为100％和60％（P〈0．01），但移植组和STI571组的2年生存率分别为77．03％和83．33％，2组患者生存率比较差异无统计学意义（P〉0．05）。结论：与异基因造血干细胞移植相比，STI571治疗慢性粒细胞白血病患者治疗相关并发症较少较轻，但获得细胞遗传学完全缓解率较低。     

Long-term leukemia-free survival after allogeneic marrow transplantation in patients with acute myelogenous leukemia

Between February 1982 and April 1995, 62 patients (37 male, 25 female) with acute myelogenous leukemia (AML) with a median age of 32 years (19–51 years) received allogeneic marrow grafts from an HLA-identical sibling (n=60) or an HLA-mismatched family member (n=2). At the time of transplant, 35 patients were in first complete remission (CR), five in second CR, eight were primary refractory, eight were in untreated relapse and six in refractory relapse. The FAB subtypes were as follows: M1 (n=17), M2 (n=13), M3 (n=6), M4 (n=19), M5 (n=6), M6 (n=1). For conditioning most patients were given total body irradiation combined with cyclophosphamide (CY,n=50) or CY and busulfan (n=9). For graft-versus-host disease prophylaxis patients received cyclosporin A (CSA) and methotrexate (MTX) (n=32), MTX alone (n=12), CSA and methylprednisone (n=5), or CSA alone (n=13). As of April 1995, probability of leukemia-free survival projected at 10 years after BMT was 60% for patients transplanted in first CR compared with 10% for patients transplanted beyond first CR. Transplant-related mortality was 11% after BMT in first CR and 39% after BMT beyond first CR. Probability of relapse projected at 10 years after BMT is 32% for patients who received transplants in first CR and 81% for patients who received transplants beyond first CR. Thus, high-dose chemo/radiotherapy followed by allogeneic marrow infusion has a high curative potential for patients with AML who receive transplants in first CR and offers the chance of long-term disease-free survival for some patients with advanced disease.