27例成人Ph染色体阳性急性淋巴细胞白血病的临床分析

目的：研究伊马替尼及造血干细胞移植治疗Ph＋急性淋巴细胞白血病（ALL）的临床疗效。方法收集初诊 Ph＋ALL患者27例,19例采用伊马替尼联合化疗诱导治疗（IVD组8例,伊马替尼联合VDLP组8例,伊马替尼联合VDP组3例）,其余8例给予VDLP常规化疗。22例达完全缓解（CR）后给予伊马替尼联合化疗序贯治疗,3例给予常规维持及巩固化疗,定期监测血常规、骨穿、ABL基因突变及转阴情况。6例行造血干细胞移植,其中1例为自体移植。结果伊马替尼联合化疗诱导治疗C R率可达89．5％,诱导死亡率为0;常规化疗组诱导C R率为50．0％,诱导死亡率为12．5％,两组相比较,差异有统计学意义（P＜0．05）。伊马替尼联合化疗诱导治疗组中位缓解持续时间为（10．0±1．4）个月,而常规化疗组仅为2．0个月（P＜0．05）。移植患者2年总生存（OS）率75．0％,无病生存期（DFS）为83．3％;未移植患者2年OS率为14．0％,DFS率为12．6％;但两组患者OS率差异无统计学意义（P＞0．05）,而DFS差异明显（P＜0．05）。BCR／ABL转阴患者的OS及DFS均明显高于未转阴患者。结论伊马替尼联合化疗诱导治疗Ph＋ALL能提高患者的CR率和缓解持续时间,造血干细胞移植能提高患者的DFS率。     

伊马替尼联合Hyper-CVAD方案治疗Ph染色体阳性急性淋巴白血病的临床观察

目的 观察伊马替尼联合Hyper-CVAD(环磷酰胺+长春地辛+吡柔比星+地塞米松或甲氨蝶呤+阿糖胞苷)方案治疗Ph染色体阳性急性淋巴白血病(Ph+ALL)患者的疗效及安全性.方法 北京军区总医院血液科2005年1月至2010年1月应用伊马替尼联合Hyper-CVAD方案治疗18例Ph+ALL患者,治疗方案为伊马替尼、Hyper-CVAD(A/B方案)序贯治疗,持续8个疗程,维持2年;同期18例Ph+ALL患者行造血干细胞移植设为对照组.结果 治疗组18例患者平均年龄33.1岁,诱导化疗获得总缓解率为100%,中位生存期为28.8(8.0～60.0)个月,1、2、3年总生存率分别为77.8%、72.2%、66.7%;对照组诱导化疗获得总缓解率为100%,中位生存期为22.5(4.0～58.0)个月,1、2、3年总生存率分别为66.7%、55.6%、50.O%,随访至2010年10月治疗组复发死亡5例,复发相关病死率为27.8%;对照组复发死亡4例,复发相关病死率为22.2%;总计治疗组死亡6例,病死率为33.3%,对照组死亡9例,病死率为50.0%.结论 伊马替尼联合Hyper-CVAD方案治疗Ph+ALL患者的生存率明显提高,中位缓解时间及生存时间超过异基因造血干细胞移植水平.

Abstract：

Objective To report the efficacy and safety of imatinib plus Hyper-CVAD chemotherapy regimen in the treatment of patients with ph chmmosome positive acute lymphocytic leukemia(Ph+ALL).Methods A sequential 2-year and 8-cycle treatment of imatinib plus Hyper-CVAD(A/B program)was administrated in 18 Ph+ALL patients treated at our hospital since January 2005 to January 2010.And another 18 Ph+ALL patients undergoing no allogeneic hematopoietie stem cell transplantation were selected as controls.Resuits Among 18 patients on chemotherapy,their average age was 33.1 years, the total response rate 100%following induction chemotherapy and the median survival 28.8(8.0-60.0)months.patients,the response rate following induction chemotherapy was 100%and the median survival 22.5(4.0-58.0)months.And the 1-,2-and 3-year overall survival rates were 66.7%.55.6%and 50.0%respectively.A recent follow-up showed that 5 patients(27.8%)died from relapse in the chemotherapy group and 4(22.2%)in the control group.The overall deaths were 6(33.3%)in the chemotherapy group and 9(50.0%)in the control group.Conclusions Imatinib plus Hyper-CVAD chemotherapy regimen is associated with significantly improved survival rates. Superior to allogeneie hematopoietic stem cell transplantation,it offers a prolonged median response time and survival time in Ph+ALL patients.     

自体造血干细胞移植治疗恶性血液病

目的　评价自体造血干细胞移植 (AHSCT)治疗恶性血液病的疗效。　方法　用 AHSCT治疗白血病及恶性淋巴瘤患者共 5 8例 ,年龄 31.9± 10 .5 (14～ 5 8)岁。其中急性非淋巴细胞白血病 (ANL L ) 30例 (CR1 2 4例 ,CR2 5例 ,CR31例 ) ,急性淋巴细胞白血病 (AL L ) 18例 (CR1 13例 ,CR2 3例 ,CR32例 ) ,慢性粒细胞白血病 (CML ) 3例 (均获血液学缓解 ) ,恶性淋巴瘤 7例 (CR4例 ,PR3例 )。预处理化疗方案选用以下药物中任意两种或三种联合 :阿糖胞苷 3～ 4g/ m2 ,环磷酰胺 4～ 6 g/ m2 ,鬼臼乙叉苷 (VP- 16 ) 0 .5～ 1.0 g/ m2 。除 5例联合全身骨髓照射 (剂量为7～ 8Gy) ,其余均单用化疗。　结果　所有患者移植后均重建造血 ,移植相关死亡 1例 (1.72 % )。ANL L、AL L CR1期移植者 3年无病生存率分别为 5 2 .4%± 4.2 %和 46 .1%± 3.5 % ,复发率分别为 37.7%± 4.5 %和 40 .5 %±6 .7%。 10例 CML 和恶性淋巴瘤患者中 ,除 1例 期恶性淋巴瘤患者复发 ,余均获持续完全缓解。　结论　为降低白血病和恶性淋巴瘤的复发率 ,提高患者的无病生存期 ,无造血干细胞供者的 CR1 期白血病及恶性淋巴瘤患者应积极行 AHSCT。     

难治复发性白血病患者造血干细胞移植后复发的分析

目的分析难治复发性白血病患者接受异基因造血干细胞移植(allo-HSCT)后复发的生存预后情况及影响因素。方法回顾性分析140例难治复发性白血病患者,其中急性髓系白血病69例,急性淋巴细胞白血病46例,慢性粒细胞白血病11例,急性混合型白血病10例,淋巴瘤白血病4例;移植前处于完全缓解(CR)49例,未缓解(NR)91例;诊断为中枢神经系统白血病(CNSL)28例。结果观察期内87例死亡,总死亡率为62.1%(87/140),复发率为39.3%(55/140),复发相关死亡为25.7%(36/140)。5年总生存率(OS)为(36.7±5.2)%,无病生存率(DFS)为(31.2±5.5)%。年龄≥40岁、移植前疾病NR状态、中枢侵犯、Ⅱ~Ⅳ°移植物抗宿主病均为影响难治复发白血病患者造血干细胞移植后复发相关死亡的独立危险因素。结论 allo-HSCT是挽救性治疗难治复发性白血病患者的有效手段,移植后复发是影响患者生存率的主要因素之一。降低移植后复发率是提高难治复发性白血病患者allo-HSCT后DFS的关键。     

难治性白血病异基因造血干细胞移植超强预处理的疗效

目的 探讨异基因造血干细胞移植超强预处理联合移植后诱导移植物抗白血病(GVL)治疗难治未缓解白血病的预处理相关毒性(RRT)和疗效。方法 18例移植前难治未缓解白血病和62例移植前完全缓解的急性白血病或慢性粒细胞白血病慢性期病人分别接受超强预处理方案和全身放疗+环磷酰胺或改良BuCY(羟基脲、马利兰、阿糖胞苷、环磷酰胺)方案(对照组)。在难治性白血病移植后30d未出现移植物抗宿主病(GVHD)病人,采用早期快速递减环孢素A或供体淋巴细胞输注诱导GVL。统计移植后RRT发生率与致死率、移植后完全缓解率、GVHD发生率、白血病复发和无病生存率等。结果 移植后除超强预处理组1例和对照组2例死于移植相关并发症外,其余病人均获得造血重建。两组总RRT发生率均为100%,各脏器RRT发生均以胃肠最常见,超强预处理组和对照组分别为83.3%和85.5%,两组口腔RRT发生率分别为44.4%和62.9%,膀胱RRT发生率分别为16.7%和33.9%,各组比较未见差异。超强预处理组RRT致死率为0,对照组为5%,两组比较无差异(P=0.341)。18例接收超强预处理病人除1例死于移植中感染外,其余病人均获完全缓解。超强预处理组和对照组移植后急性GVHD发生率分别为11.8%和18.3%,移植后3年估计无病生存率分别为(61.2±12.3)%和(65.0±7.4)%(P=0.6311)。结论 连续序惯超强预处理方案能提高移植前未缓解的难治性白血病移植后完全缓解率和无病生存率,不增加移植中RRT发生率和致死率。     

激活骨髓自体移植治疗急性早幼粒细胞白血病

目的　探讨激活骨髓 (ABM)自体移植作为急性早幼粒细胞白血病 (APL)缓解后巩固强化治疗的意义。方法　 31例病人 ,第一次完全缓解 (CR1) 2 7例、CR2 3例、第二次复发部分缓解 (PR) 1例 ;移植预处理方案 :2 7例接受MACC(马法兰、阿糖胞苷、环磷酰胺、环己亚硝脲 )方案 ,5例用TBI +CY(全身放疗 +环磷酰胺 )方案 ;荧光原位杂交测定PML/RARα融合基因 ;用Kaplan Meier生存曲线评估移植后无病生存率 ,COX回归模型分析性别、PML/RARα阳性、移植前状态 (CR1与CR2和PR)、初治时白细胞 (WBC)和血小板 (PBC)值对无病生存的影响。结果　CR1病人移植后无一例复发 ,移植后无病生存期 3～ 113个月、中位无病生存期 4 6个月 ,5年无病生存率为 10 0 % ;CR2病人 1例于移植后 19个月复发 ,另 2例分别无病生存为 7与 4 8个月 ;PR患者在移植后获CR 8个月复发。移植后全部病人均获得造血重建 ,无一例死于移植相关并发症。多因素分析长生存与移植前状态相关 (P <0 .0 5 ) ,而与性别、PML/RARα阳性、初诊时WBC和PBC数无关 ;诱导缓解后PML/RARα阳性与初诊时WBC和PBC数相关。结论　激活骨髓自体移植治疗CR后的APL病人能降低复发率和提高无病生存率、尤是CR1后的APL病人。     

Ph染色体阳性成人急性淋巴细胞白血病患者的免疫表型及临床特征

目的研究ｐｈ染色体阳性成人急性淋巴细胞白血病（Ｐｈ＋ＡＬＬ）患者的临床及生物学特征。方法５１例初治Ｐｈ＋ＡＬＬ，进行细胞形态学／细胞化学、细胞遗传学及免疫分型检查。诱导治疗３８例患者，３２例采用ＤＯＰ方案（柔红霉素、长春新碱、泼尼松），６例ＤＯＰ加左旋门冬酰胺酶（ＤＯＰＬ）方案。２例缓解后采用自体骨髓移植（ＡＢＭＴ）。结果５１例Ｐｈ＋ＡＬＬ在同期１５８例ＡＬＬ中占３２．３％。Ｐｈ＋患者年龄较大，外周血白细胞计数及原幼细胞比例高，ＦＡＢ分型以Ｌ２常见，ＣＤ１０、ＣＤ１９高表达，ＣＤ３４阳性率也较高。完全缓解率为４２．１％，达缓解的中位时间５４天，中位缓解期４．５月。２例ＡＢＭＴ者已分别缓解２２及３３个月。结论Ｐｈ＋ＡＬＬ患者年龄较大，以Ｌ２亚型及Ｂ－ＡＬＬ、ＣＤ３４阳性多见，缓解率低，达缓解时间长，缓解期短。     

异基因造血干细胞移植治疗Ph+急性淋巴细胞白血病

目的:探讨用于治疗Ph 急性淋巴细胞白血病(philadelphia chromosome positive acute lymphoblastic leukemia,Ph ALL)时异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,Allo-HSCT)的时机和供者的选择.方法:总结北京大学血液病研究所自2000年3月至2004年7月采用Allo-HSCT治疗Ph ALL患者32例.其中移植前处第一次完全缓解(complete remission,CR1)期23例,非CR1患者9例.干细胞来源:同胞相合供者12例,非血缘脐带血4例,非血缘志愿供者3例,HLA不合的亲缘供者13例.危险因素筛选采用COX回归分析,时间依赖的率的计算采用Kaplan-Meier分析,率的比较采用Log-rank检验.结果:本组患者4年存活率(overallsurvival,OS)57.19%,无病存活(leukemia-free survival,LFS)37.09%,复发率(relapse incidence,RI)56.36%.单因素分析:在移植前处CR1患者组比非CR1患者OS高(74.50%vs22.22%,P=0.004 6)、LFS高(49.06%vs11.11%,P=0.005 7)、RI低(44.80%vs84.76%,P=0.0157);MBCR/ABL组比mBCR/ABL组OS高(100%vs40.91%,P=0.031 8)、LFS高(75%vs17.72%,P=0.005 7)、RI低(25%vs77.88,P=0.0116);HLA不合亲缘组与HLA全合同胞组OS相近(52.65%vs55.56%,P=0.624 7)、LFS相近(45.13%vs30%,P=0.831 5)、RI也相近(50.77%vs60.62%,P=0.821 7).多因素分析:BCR/ABL融合蛋白类型是影响LFS和RI的高危因素[前者P=0.005,Exp(B)=9.971,后者P=0.006,Exp(B)=9.488],移植前的疾病状态和BCR/ABL的类型是影响OS的危险因素[P值分别为0.010和0.038,Exp(B)值分别为4.532和37.537].结论:治疗Ph ALL应争取在CR1期进行Allo-HSCT,如果对化疗耐药,可用伊马替尼(格列卫),挽救性治疗争取在CR后移植.对Ph ALL配型不合的亲缘供者(半相合)移植同样可以作为常规选择.对融合蛋白为m型者要更加重视移植后复发的检测和预防.     

Glut5在Ph+急性淋巴细胞白血病伊马替尼耐药中的机制研究

目的采用费城染色体阳性急性淋巴细胞白血病（Ph+ALL）伊马替尼耐药细胞株SUP-B15/R研究伊马替尼耐药的可能机制。方法通过基因芯片分析法对比找出伊马替尼耐药株SUP-B15/R与敏感株SUP-B15/S之间表达差异的基因,筛选出可能与耐药相关的基因SLC2A5,分别采用实时荧光定量PCR（qPCR）和Western blot进一步验证SLC2A5及其编码蛋白葡萄糖转运体5（Glut5）在SUP-B15/R与SUP-B15/S之间表达的差异。采用MTT实验检测果糖对SUP-B15/S细胞伊马替尼敏感性的影响,以及qPCR检测相关信号通路的改变,探究Glut5表达增加在SUP-B15细胞伊马替尼耐药中的作用。结果基因芯片结果发现,与细胞代谢相关的SLC2A5基因在SUP-B15/R中高表达,qPCR和Western blot实验进一步验证了上述结果。而果糖处理后SUP-B15/S细胞对伊马替尼的敏感性下降,IC50由（44.50±2.38 ）μmol/L增加到（64.71±1.69） μmol/L,同时Glut5、PI3K、AK mRNA表达增强。结论SUP-B15/R细胞高表达SLC2A5,Glut5高表达促进细胞对果糖的吸收,激活伊马替尼作用下受到抑制的PI3K/AKT信号通路,导致SUP-B15细胞对伊马替尼耐药。     

Ph^＋急性淋巴细胞白血病与慢性粒细胞白血病急淋变的临床特征分析

目的比较Ph＋急性淋巴细胞白血病（ALL）与慢性粒细胞白血病（CML）急淋变的临床特征。方法回顾性分析Ph＋ALL患者24例和CML急淋变患者28例的临床资料,比较两组患者的临床资料、细胞免疫表型分析结果以及临床疗效。结果 CML急淋变组肝肿大和脾脏肿大比例显著高于Ph＋ALL组（P〈0.05或P〈0.01）。CML急淋变组WBC〉10×109/L比例显著高于Ph＋ALL组（P〈0.05）。治疗前两组融合基因拷贝数差异无统计学意义（P〉0.05）。16例Ph＋ALL患者治疗后达到缓解,Bcr/abl融合基因拷贝数平均（0.4±0.1）,10例CML急淋变患者达到血液缓解,Bcr/abl融合基因拷贝数平均（50.1±15.4）,两组比较差异有高度统计学意义（P〈0.01）。Ph＋ALL组CR发生率显著高于CML急淋变组（P〈0.05）,平均生存率显著长于CML急淋变组（P〈0.01）。结论 Ph＋ALL与CML急淋变具有不同的临床特征和不同的遗传性特征。Ph＋ALL诱导完全缓解后,Ph染色体呈阴性,而CML急淋变诱导缓解后Ph染色体仍然存在。Ph＋ALL完全缓解率高于CML急淋变患者,平均生存时间长于CML急淋变患者。     

慢性髓细胞白血病向T淋巴细胞淋巴瘤/白血病急变一例和文献复习

目的介绍1例慢性髓细胞白血病(CML)向T淋巴细胞淋巴瘤/白血病(T-LBL/ALL)急变病例并复习文献,以提高对该病的认识。方法对1例CML向T-LBL/ALL急变患者的临床特征、细胞遗传学改变及其随访资料进行分析,并结合文献讨论本病的临床特点、诊断与鉴别诊断和治疗。结果采用荧光原位杂交(FISH)方法确诊1例髓外发生T-LBL/ALL急变的CML患者。所有文献报道的47例患者中,男女发病比例为2．6∶1,年龄19～72岁,中位数为41岁,约90%者有CML病史,但无CML病史不能排除本病。＞75%者有髓外病变,常见部位包括淋巴结、肝脏、脾脏和纵隔,而骨髓受累者不到50%。所有病例均经细胞形态学、免疫组织病理学和细胞或分子遗传学技术如核型分析或(和)Southern免疫印迹法或逆转录聚合酶链反应(RT-PCR)等检查而诊断。与继发于或同时存在于CML的Ph(-)T-LBL/ALL和原发Ph( )T-LBL/ALL鉴别非常困难,主要决定于FISH技术证实淋巴系肿瘤细胞或(和)形态正常的血细胞是否存在bcr-abl重排。常规化疗预后差,化疗联合伊马替尼治疗可能会改善部分患者的预后。结论CML向T-LBL/ALL急变是一种罕见的疾病,FISH技术在本病的诊断和鉴别诊断中起关键作用。在伊马替尼治疗时代,本病与其他相似疾病之间的鉴别可能具有重要的临床意义。     

难治性白血病异基因造血干细胞移植超强预处理的疗效

OBJECTIVE: To explore the regimen-related toxicity (RRT) and therapeutic effects of very-high-dose conditioning regimen combined with induction of graft-versus-leukemia (GVL) effects in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory leukemia with unattainable complete remission (CR) before transplantation. METHODS: Eighteen patients who failed to obtain CR before transplantation received very-high-dose conditioning regimen protocol (experimental group), and 62 patients with acute leukemia with CR or with chronic myeloid leukemia in the chronic phase before transplantation received total body irradiation plus cyclophosphamide (CTX) or modified BuCY (hydroxyurea, busulfan, Ara-C, CTX) protocol (control group). In patients with refractory leukemia who did not develop graft-versus-host disease (GVHD) 30 d after the transplantation, GVL was induced by rapid reduction of the dosage of cyclosporin A or by donor lymphocytic infusion. The incidence and mortality of RRT and the rates of CR, GVHD and leukemia relapse after transplantation were investigated. Kaplan-Meier survival analysis model was used to estimate the disease-free survival (DFS) rate at 3 years post-transplantation. RESULTS: Except for one patient in the experimental group and two in the control group who died of transplantation- related complications, all the other patients obtained hematopoietic reconstitution. The total incidence of RRT was 100% in both groups, involving most frequently the stomach and intestines at the rate as high as 83.3% in the experimental group and 85.5% in the control group. RRT involving the oral cavity occurred in 44.4% and 62.9%, and that involving the bladder in 16.7% and 33.9% of the cases in the experimental group and control group, respectively, all similar between the groups (P=0.823, 0.172 and 0.244, respectively). The RRT mortality was 0 and 5% in the experimental and control groups, respectively (P=0.341). With the exception of one patient who died of infection, all the other patients treated with very-high-dose conditioning regimen obtained CR. The incidences of acute/chronic GVHD were 58.8%/92.6% and 40.0%/55.8%, respectively, in the experimental and control groups. The incidence of leukemia relapse was 11.8% and 18.3%, and DFS at 3 years after transplantation was (61.2+/-12.3)% and (65.0+/-7.4)% (P=0.6311) in the two groups, respectively. CONCLUSION: Consecutive very-high-dose conditioning regimen combined with GVL induction after transplantation can increase the rate of CR and DFS, without increasing RRT incidence and mortality in allo-HSCT for the refractory leukemia with unattainable CR pre-transplantation.     

异基因外周血干细胞移植治疗高危白血病

目的　探讨异基因外周血干细胞移植(allo-PBSCT)治疗高危白血病的疗效。方法　25例高危白血病患者,中位年龄34（5.5～52）岁,接受了HLA配型相合同胞供者外周血干细胞移植,其中急性白血病（AL）15例,（第一次完全缓解1例,为Ph染色体阳性,第二次及以上完全缓解期7例,复发7例,包括2例异基因骨髓移植(BMT)后复发;慢性粒细胞性白血病（CML）4例;（第2次慢性期、加速期、急变期、BMT后复发各1例）;骨髓增生异常综合征(MDS)6例,移植物抗宿主病（GVHD）预防方案采用经典环孢霉素（CsA）加氨甲蝶呤（MTX）。结果　所有患者均植活,中性粒细胞数恢复至≥0.5×109/L和血小板数≥20×109/L的中位时间分别为移植后14(10～18) d和11（7～45） d。发生II度及以上急性GVHD13例,包括1例III度GVHD,未发生IV度急性GVHD。23例可评估患者中16例(70%)诊断慢性GVHD。移植相关死亡率为16%,复发6例,4例经回输供者淋巴细胞获得再次缓解。19例患者无病存活,中位随访时间为304（94～1 963） d。2年总生存率、无病生存率及复发率分别为64%、58%及25%。结论　allo-PBSCT可治疗高危白血病患者,降低移植后复发率,延长无病生存。对有高危因素的血液系统恶性肿瘤患者,选择PBSCT替代骨髓移植更有优势。     

Chronic myelogenous leukaemia (CML): an update

The management of chronic myelogenous leukaemia (CML) has undergone a major change over the past 5 years. All newly diagnosed patients of CML are candidates for imatinib mesylate therapy. Almost 95% of patients with early chronic phase CML achieve complete haematological remission (CHR) and nearly 80% achieve complete cytogenetic response (CGR; 0% Philadelphia [Ph] chromosome-positive metaphases). These responses are stable in most patients with a risk of relapse of 4%-6% per year. For patients with advanced CML (accelerated phase and blast crisis), achievement of CHR and major (complete and partial) CGR occurs in 25%-37% and 10%-30% of patients, respectively. Most investigators agree that patients who fail to achieve CHR by 12 weeks, have partial cytogenetic response (< 35% Ph-positive metaphases) at 12 months, have CGR by 18 months, who relapse after initial response to imatinib, and those with a high Sokal score or in an advanced phase of CML should be considered for allogeneic stem cell transplantation (SCT). Despite Ph negativity with imatinib treatment, most patients continue to remain BCR-ABL positive on molecular studies, and require treatment indefinitely. Identification of patients at high risk for relapse and understanding the mechanisms to unravel resistance to imatinib are current areas of active research.     

无染色体异常的急性白血病自体造血干细胞移植的疗效

目的 评价自体外周血造血干细胞移植(PBSCT)治疗无染色体异常的急性白血病(AL)的疗效。方法 12例急性淋巴细胞性白血病(ALL)和10例急性髓细胞性白血病(AML)病人,在诱导治疗获得第一次缓解后(CR1)分为自体PBSCT组和继续常规化疗组对照研究。结果 自体移植组中5例CR1的AML,2年以上无病生存率(DFS)为80％;6例CR1的ALL,2年以上DFS为60％,而且自体移植后存活的病人均无生活质量问题。采用常规化疗的病人,5例CR1的AML,2年以上DFS仅为40％;6例CR1的ALL,2年以上DFS为40％,提示自体移植疗效好于常规化疗。结论 对于无染色体异常核型的中危和低危急性白血病病人,若无HLA相合供体,应首选自体PBSCT作为巩固治疗。     

Activity and side effects of imatinib in patients with gastrointestinal stromal tumors: data from a german multicenter trial

Gastrointestinal stromal tumors (GIST) are mesenchymal tumors that in the past were classified as leiomyosarcomas or leiomyomas not responding to standard sarcoma chemotherapy. In several phase I and II trials the efficacy and safety of imatinib was shown before the largest trial ever performed in a single sarcoma entity revealed response rates (CR/PR) of 52 %. This multicenter phase II trial presented here was performed to open access to imatinib for patients with unresectable or metastastatic GIST when the EORTC 62005 trial had been closed before imatinib was approved in Germany. It was designed to follow the best clinical response and to assess the efficacy, safety and tolerability of imatinib 400mg/d in patients with unresectable or metastatic gastrointestinal stromal tumor. - 95 patients were treated in this trial with Imatinib 400mg/d. Four patients (4.6 %) attained a complete response and 26 patients (29.9%) a partial response to imatinib treatment. Forty-one patients (47.1 %) revealed a stable disease and 16 patients (18.4 %) had a progressive disease. - Of the progressive patients 22% showed a partial response and 67 % showed stable disease after escalating the dose to 800 mg. According to SWOG tumor response classification, 66 patients (70%) were free of progression within the first year of treatment. - Seventy-one patients (74.7%) experienced adverse events or severe adverse events with a suspected relationship to the study drug. Among these, the most common were nausea (n=27 patients, 28.4 %), eyelid edema and peripheral edema in 23 patients each (24.2 %), diarrhea in 20 patients (21.1 %), muscle cramps in 15 patients (15.8 %) and fatigue in 13 patients (13.7 %). - Imatinib 400 mg/d led to disease stabilisation in 81,6% of patients with unresectable or metastatic malignant GIST. Thirty-four percent of patients attained a tumor remission (partial or complete response). The safety profile of imatinib based on adverse event assessment is favorable. Imatinib is generally well tolerated in patients with gastrointestinal stromal tumors.     

An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation

Objective To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.Methods Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n = 11 ), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n =9).Results Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response.Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia,and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.Conclusion Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL)effect than DDL infusion.     

全身照射加足叶乙甙联合自体造血干细胞移植治疗非霍奇金淋巴 …

目的 评价全身照射（ＴＢＩ）加足叶乙甙（ＶＰ－１６）作为自体造血干细胞移植（ＡＨＳＣＴ）的预处理方法治疗非霍奇金淋巴瘤（ＮＨＬ）的疗效和安全性。方法 ２４例诱导治疗缓解的中高度恶性ＮＨＬ进行ＡＨＳＣＴ,其中２３例为首次缓解,１例为第３次缓解。自体骨髓移植（ＡＢＭＴ）１０例,自体外周血干细胞移植（ＡＰＢＳＣＴ）１４例,采用ＴＢＩ８００（７００－８５０）ｃＧｙ／Ｖｐ－１６７５７（２３－１１４０）ｍｇ／     

异基因造血干细胞移植治疗伊马替尼耐药Ph染色体阳性白血病

目的 探讨造血干细胞移植(HSCT)作为甲磺酸伊马替尼(IM)耐药的费城染色体阳性(Ph+)白血病挽救性治疗的疗效.方法 回顾性分析2002年7月至2006年8月北京大学人民医院血液病研究所住院的14例IM耐药Ph(+)白血病患者行异基因(allo)-HSCT的效果,其中复发/难治急性淋巴细胞白血病(ALL)3例,慢性髓性白血病加速期(CML-AP)1例,慢性髓性白血病急变期(Bc)10例;7例行HLA配型完全相合同胞间移植,7例行HLA配型不相合亲缘移植;采用重组人粒细胞集落刺激因子(rhG-CSF)动员的骨髓(BM)加外周血干细胞(PBSC)混合移植8例,单用PBSC移植6例;10例患者给予预防或治疗性rhG-CSF动员后的供者淋巴细胞输注(DLI).结果 所有病例均达到完全供者型造血重建,移植后中性粒细胞和血小板植活的中位时间分别为16 d和13 d;发生Ⅱ度急性移植物抗宿主病(aGVHD)7例,Ⅲ度aGVHD 2例,局限型慢性移植物抗宿主病(cGVHD)4例,广泛型cGVHD 6例;血液学复发9例;无早期移植相关死亡.结论 联合应用多种方法预防白血病复发,HSCT可作为IM耐药Ph(+)白血病患者重要的挽救治疗选择.     

BCR-ABL基因阳性成人急性淋巴细胞白血病29例临床分析

目的总结BCR-ABL融合基因阳性的急性淋巴细胞白血病（acute lymphoblastic leukemia,ALL）患者的临床特点、疗效和预后。方法回顾分析29例确诊为BCR-ABL基因阳性的ALL患者,予传统化疗、伊马替尼和异基因造血干细胞移植治疗,随访期3～80月,评价治疗效果。结果178例ALL患者中,BCR-ABL基因阳性者29例（16.3%）,其中B细胞性28例,T细胞性者1例。14例患者在首1～2个疗程化疗后获得完全缓解（48.3%）,部分缓解者1例（3.4%）,2例在首2个疗程未获CR后加用伊马替尼获得骨髓细胞学完全缓解（10.3%）,无效12例（41.4%）。29例患者中位生存期14.5月。伊马替尼联合传统化疗化疗者完全缓解率80%,高于单用传统化疗者（50%（）χ2=5.894,P〈0.01）,生存期（18.6月）大于单用传统化疗未进行移植者（11.1月）（t=2.469,P〈0.05）。结论BCR/ABL融合基因阳性的ALL患者传统化疗疗效差,联合伊马替尼可提高完全缓解率和生存期,异基因造血干细胞移植可使部分患者长期无病生存。