ABO血型不合异基因造血干细胞移植临床观察

目的：探讨ABO血型不合异基因造血干细胞移植治疗血液病的临床疗效和近远期并发症。方法：对15例包括恶性血液病5例(多发性骨髓瘤1例、急性白血病3例、慢性粒细胞白血病1例)、再生障碍性贫血一阵发性睡眠性血红蛋白尿2例、重型再生障碍性贫血8例，进行同胞供者外周血干细胞移植、外周血联合骨髓造血干细胞移植和无关供者脐血造血干细胞移植。观察植入效果、血型的转变、以及移植近远期并发症。结果：15例患者均恢复造血功能，13例植入混合性嵌合体(MC)、其中5例由MC转变为供者完全性嵌合体(CC)，8例长期保持MC状态，2例未植入。所有患者在输注移植物时出现轻微短暂的血红蛋白尿，无严重急性溶血和迟发性溶血发生，无急性移植物抗宿主病(aGVHD)，1例局部型慢性移植物抗宿主病(cGVHD)，1例广泛型cGVHD。在造血植入的患者，脐血移植4例保持MC状态、血型未转变，其余干细胞移植血型在1～2个月转变。结论：ABO血型不合异基因造血干细胞移植治疗血液病疗效肯定，对移植物和供受者体内凝集素的处理十分重要。     

减低剂量预处理对异基因造血干细胞移植治疗恶性血液病疗效观察

目的:探讨应用减低剂量的氟达拉宾、白消安和环磷酰胺(FBC)方案预处理对异基因造血干细胞移植(alloHSCT)治疗恶性血液病疗效的影响。方法:19例恶性血液病患者移植前进行减低剂量的FBC预处理。采用磷酸氟达拉宾(Flud)30mg/m2·d-1静脉滴注5d。白消安(Bu)0.6mg/kg、4次/d,共3d。环磷酰胺(CTX)30mg/kg·d-1静脉滴注,共2d,随后施行HLA配型的同胞或父亲供者的造血干细胞移植。术后采用环孢素及霉酚酸酯预防移植物抗宿主病(GVHD)。结果:全部患者的造血功能均获得快速重建。白细胞升至1.0×109/L以上,中位时间为(11.4±4.6)d。中性粒细胞升至0.5×109/L以上,中位时间为(11.9±6.7)d;血小板升至20×109/L以上,中位时间为(12.2±3.5)d。供者细胞完全植入15例,混合嵌合性植入4例,1例出现宿主排斥移植物(HVG)反应,进行供者淋巴细胞输注(DLI)2次后,达到完全供者嵌合。11例出现急性GVHD(57.89%),7例出现慢性GVHD(36.83%),2例HLA配型不完全相合者死于急性GVHD。结论:减毒的FBC预处理方案allo-HSCT治疗恶性血液病疗效肯定,并发症少,是治疗恶性血液病的有效方法。     

G-CSF动员后异基因骨髓联合外周血干细胞移植治疗血液病

目的 探讨粒细胞集落刺激因子(G-CSF)动员的异基因骨髓与外周血干细胞混合移植后造血重建、移植物抗宿主病(GVHD)、复发及生存情况.方法 45例血液病患者进行了动员后的异基因骨髓联合外周血干细胞混合移植,人白细胞抗原(HLA)全合37例,1～3个位点不合8例.38例恶性病中32例采用清髓性预处理,6例为减低强度预处理;7例重型再生障碍性贫血(SAA)均采用环磷酰胺联合兔抗人胸腺细胞球蛋白(ATG)及甲泼尼龙预处理.采用环孢素联合霉酚酸酯预防移植物抗宿主病,HLA不全相合患者加用ATG.供者给予G-CSF连续5天皮下注射,注射后第5天采集外周血干细胞,第7天采取骨髓血.结果 45例患者均获得快速造血重建,中性粒细胞绝对计数≥0.5×109/L,血小板≥20×109/L的中位时间分别为移植后的12(8～18)天和16(10～28)天.10例发生了急性GVHD(22%),Ⅱ度以上1例.可评估的42例患者中16例出现了慢性GVHD,7例为广泛型(16%).复发9例,死亡11例,其余34例中位随访时间16月(10～46月),可评估的2年无病生存率为75%.结论 G-CSF动员后的异基因骨髓联合外周血干细胞移植治疗血液病可获快速造血重建,移植相关死亡率及重度急、慢性GVHD的发生率低,复发率不增高.     

异基因造血干细胞移植治疗恶性血液病(附9例报告)

9例恶性血液病患者 ,采用异基因外周血干细胞移植 ( allo- HSCT)治疗 7例 ,外周血与骨髓干细胞混合移植 2例 ;供者均为人白细胞相关抗原 ( HL A)完全相合同胞兄妹。预处理方案用马利兰 ( BU)、环磷酰胺( CY) ,环孢霉素 A ( Cs A)联合短程甲氨蝶呤 ( MTX)预防移植物抗宿主病 ( GVHD)。结果 :患者治疗后均重建造血 ,中性粒细胞≥ 0 .5× 10 9/ L 的中位数为 14天 ,血小板≥ 2 0× 10 9/ L 的中位数为 16天。发生急性 GVHD5例 ,慢性 GVHD2例 ,肝静脉闭塞病 ( VOD) 1例 ,巨细胞病毒血症 9例。2例 ABO血型不合者移植后未发生溶血及纯红再障。1例耐药复发淋巴瘤 ,供、受者均为乙肝病毒携带者 ,移植后达完全缓解。中位随访时间 15个月 ,无病生存 8例。认为 allo- HSCT是治疗恶性血液病 (尤其是耐药复发者 )的有效方法 ,ABO血型不合及乙肝供者不是移植的障碍     

供受者血型相合母亲供者和血型不合父亲供者对单倍体异基因造血干细胞移植预后的影响

目的 比较供受者血型相合母亲供者和血型不合父亲供者对单倍体异基因造血干细胞移植(haplo-HSCT)预后的影响.方法 回顾性纳入接受haplo-HSCT的恶性血液病患者160例,其中供受者血型相合母亲供者(母亲血型相合组)40例,供受者血型不合父亲供者(父亲血型不合组)120例(按1:3配对纳入).收集两组患者的临床...     

异基因造血干细胞移植治疗白血病20例临床观察

目的探讨不同类型异基因造血干细胞移植(allo-HSCT)治疗白血病的疗效、造血重建及存活情况。方法哈尔滨血液病肿瘤研究所2003年3月至2006年7月进行异基因造血干细胞移植的白血病患者20例,其中同胞间人类白细胞抗原(HLA)相合的异基因外周血造血干细胞移植(allo-PBSCT)12例,无亲缘关系HLA不全相合脐血移植(UCBT)4例,无关供者的异基因外周血干细胞移植(其中1例HLA-CW位点亚型不合)3例,无关供者骨髓移植1例(经过去除红细胞处理)。结果19/20受者获造血重建,UCBT患者造血重建速度较HLA相合的同胞allo-PBSCT慢,异基因造血干细胞移植后20例患者中发生急性移植物抗宿主病(aGVHD)7例,其中4例Ⅰ~Ⅱ度,3例Ⅲ~Ⅳ度。3例患者死于复发,3例死于移植物抗宿主病(GVHD),另15例至今仍无病存活,中位存活时间30(1~41)个月。结论allo-HSCT是目前治愈白血病的有效方法,对于无同胞HLA相合的供者,选择较高细胞数量,HLA1~2个位点不合的UCBT仍然有效、可行。     

HLA半相合非清髓性造血干细胞与间充质干细胞共移植治疗重症再生障碍性贫血1例

目的:观察HLA半相合非清髓性造血干细胞与间充质干细胞(MSC)共移植治疗重症再生障碍性贫血(SAA)的疗效及安全性。方法:1例24岁男性SAA患者。应用非清髓性预处理方案,进行HLA半相合异基因外周血造血干细胞和MSC共移植。移植rhG-CSF动员的供者外周血单个核细胞9.22×108/kg,CD34 细胞8.56×106/kg,及体外扩增培养的供者骨髓MSC2.12×105/kg。结果:移植后 12d中性粒细胞数>0.5×109/L, 21d WBC4.5×109/L,Hb99g/L,PLT108×109/L。经HLA配型,红细胞亚型和VNTR检测,为供者型完全嵌合体。随访14个月,无急、慢性移植物抗宿主病(GVHD)发生。结论:HLA半相合非清髓性造血干细胞与MSC共移植治疗SAA是安全有效的方法。     

单倍型相合骨髓移植治疗难治复发恶性淋巴瘤初步观察

目的:探讨应用单倍型未去T细胞的异基因骨髓移植(allo-BMT)治疗难治复发恶性淋巴瘤的疗效、造血重建、并发症及生存情况。方法:采用清髓性未去T细胞亲缘单倍型相合allo-BMT治疗11例难治性晚期淋巴瘤患者。供者用粒细胞刺激集落因子(G-CSF)皮下注射,连续7d后采髓,预处理方案采用环磷酰胺、全身照射及阿糖胞苷(CyTBI加Ara-C)。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、短程氨甲碟呤、抗胸腺细胞球蛋白、CD25单克隆抗体及霉酚酸酯。结果:患者移植后均获造血重建,中性粒细胞>0.5×109/L及PLT>20×109/L的平均时间分别为17.2及21.3d,植入证据检测证实为完全供者造血。4例发生急性GVHD(aGVHD),3例发生慢性GVHD(cGVHD),中位随访1136(31～2521)d,2例死于感染,1例死于aGVHD,1例死于复发,无病生存7例。结论:清髓性未去T细胞亲缘单倍型相合allo-HSCT是治疗伴骨髓侵犯以及自体造血干细胞移植后复发难治性晚期恶性淋巴瘤有效方法,如有合适供者,可考虑作为年轻晚期患者的挽救治疗。     

母供子非去T细胞性单倍体异基因造血干细胞移植治疗恶性血液病

目的:对18例恶性血液病进行母供子非去T细胞性单倍体异基因造血干细胞移植(Allo-HSCT)治疗,探讨其疗效及毒性反应。方法:6例急性髓系白血病(AML-M23例,AML-M41例,AML-M5b2例),3例慢性粒细胞白血病(伴骨髓纤维化1例),8例急性淋巴细胞白血病(ALL),非霍奇金淋巴瘤(Ⅳ期B组)1例,以母亲为供者进行非去T细胞性单倍体Allo-HSCT。供者动员方案:G-CSF300μg/12h×5d后采集造血干细胞。输注D34 细胞(3.58~8.90)×106/kg。预处理方案为:MeCCNC250mg·m-2·d-1×1d,Ara-C4g·m-2·d-1×2d,Bu4mg·kg-1·d-1×3d,CTX1.8g·m-2·d-1×2d。ALL患者以全身放疗(TBI)代替Bu。以CsA、MMF、MTX和ALG预防移植物抗宿主病(GVHD)。结果:所有患者均顺利完成预处理。移植后发生急性GVHD16例、慢性GVHD10例,出血性膀胱炎1例。全部患者在移植后10~20d获造血重建。18例患者中12例存活。结论:非去T细胞性单倍体Allo-HSCT是治疗恶性血液病的一种安全、有效的方法;同时提示在以后的单倍体异基因造血干细胞移植中优先选择母亲供体,对降低GVHD的严重程度、提高移植成功率是有帮助的。     

异基因造血干细胞移植治疗恶性血液病临床观察

目的观察异基因造血干细胞移植(allo-SCT)治疗恶性血液病的疗效.方法选择HLA-A、B、DR位点完全相同的同胞作为供者,对13例恶性血液病患者进行allo-SCT,其中急性白血病10例,慢性白血病2例,恶性淋巴结瘤1例.采用BUCY预处理方案7例,TBI CY预处理方案4例,非清髓预移植方案2例.输入CD34细胞数(4.6～11.4)×106/kg.患者均用环孢菌素A加甲氨蝶呤预防移植物抗宿主病.结果 11例清髓性移植患者移植后9～19天外周血白细胞≥1.0×109/L,14～34天血小板≥20×109/L.移植后4例死于移植相关并发症,9例完全缓解,中位生存期26(8～73)个月.结论 allo-SCT治疗恶性血液病疗效可靠.     

非清髓异基因造血干细胞移植治疗恶性血液病临床分析

目的:观察非清髓异基因造血干细胞移植(NST)治疗恶性血液病的疗效及并发症的处理。方法:对33例恶性血液病患者施行NST并随访观察。预处理方案应用氟达拉滨30mg.m-2.d-1(-7～-2d),马利兰4mg.kg-1.d-1(-6～-5d),环磷酰胺350mg.m-2.d-1(-3～-2d),HLA不全相合者加用抗淋巴细胞球蛋白(ALG)750mg/d(-2～-1d)。移植物抗宿主病(GVHD)预防应用环孢素A(CsA)和骁悉(MMF)。应用美司那、大量水化、碱化尿液预防出血性膀胱炎。应用凯时(前列腺素E1)预防肝静脉闭塞病(VOD)。结果:全部患者均成功植入,造血重建速度快。中性粒细胞0.5×109/L的中位时间是+13(+10～+16)d,血小板20×109/L的中位时间是+12(+9～+25)d。3例患者在+100d左右出现间质性肺炎,血CMV-DNA阳性,应用更昔洛维抗病毒等治疗后均痊愈。17例患者发生急性移植物抗宿主病(aGVHD)(51.5%),Ⅰ度患者10例(30.3%),Ⅱ度患者5例(15.2%),Ⅲ度患者2例(6.06%)。有20例患者出现慢性移植物抗宿主病(cGVHD)(64.5%),其中局限型15例(48.4%),广泛型5例(16.1%)。有3例患者出现VOD(9.1%),5例患者出现出血性膀胱炎(15.2%),经积极治疗均有效控制。中位随访37(2.5～58.0)个月,现存活24例(72.7%),9例死亡(27.3%),5例疾病复发(15.2%)。9例死亡患者中7例死于GVHD,2例死于疾病复发。结论:NST植入可靠,造血重建快,复发率低,移植相关并发症感染、出血性膀胱炎、VOD发生率低,治疗安全、有效。但GVHD发生率较高,是导致死亡的主要原因。     

Long-term follow-up after nonmyeloablative allogeneic hematopoietic stem cell transplantation for systemic sclerosis

Systemic sclerosis (SSc) characteristically consists of fibrotic changes in various organs, and immunological abnormality is the main cause of the disease. Although high-dose immunosuppressive therapies with autologous or allogeneic hematopoietic stem cell support can reverse the disease course, they have a high treatment-related mortality. We report the successful use of nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for SSc. A 40-year-old woman with diffuse scleroderma and interstitial pneumonia underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical sibling after conditioning with low-dose total-body irradiation and fludarabine. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and mycophenolate mofetil. No infection or acute GVHD developed. One year after transplantation, the patient developed membranous glomerulopathy caused by chronic GVHD that was successfully treated with prednisolone. The patient's skin score decreased dramatically, and her pulmonary function is stable 4 years after transplantation. Nonmyeloablative allogeneic HSCT may be more effective than conventional therapies for SSc.     

异基因造血干细胞移植治疗高危恶性血液病

目的 分析HLA配型相合同胞供者异基因造血干细胞移植（allo-HSCT）治疗高危恶性血液病的疗效及影响疗效的相关因素。方法 回顾性分析90例有高危因素的恶性血液病患者,其中急性髓细胞白血病（AML）43例,急性淋巴细胞性白血病（ALL）28例,急性混合细胞性白血病（AHL）2例;移植前处于第1次完全缓解期（CR1）11例,均为Ph染色体阳性,第二次及以上CR期23例,未缓解／复发39例;骨髓增生异常综合征（MDS）-难治性贫血伴原始细胞增多或难治性贫血伴原始细胞增多一转化型17例。预处理方案采用全身照射加环磷酰胺（CY／TBI）方案11例,白消安加环磷酰胺方案79例。干细胞来源包括骨髓移植（BMT）27例,外周血造血干细胞移植（PBSCT）30例,BMT＋PBSCT33例;移植物抗宿主病（GVHD）预防采用经典环孢素A加短程甲氨蝶呤（MTX）。平均随访时间为15个月。结果 至随访终点,62．2％（56／90）存活,55．5％（50／90）无病存活,31．1％（28／90）复发。HSCT后预计4年累积总体生存率（OS）为45．5％,无病生存率（DFS）为34．9％。移植前处于CR、未缓解／复发和MDS患者HSCT后4年的累积0s分别为54．0％、28．2％和70．1％（P=0．027）。发生0～Ⅰ和Ⅱ～Ⅳ度GVHD的患者HSCT后的4年OS分别为57．6％和26．7％（P=0．015）,而患者性别、年龄、移植前有无脑膜白血病、预处理方案、干细胞来源均不是OS,DFS及复发的影响因素。多因素分析表明,移植前处于CR期者长期生存率明显提高,而ALL长期生存率明显低于AML／MDS。结论 对有高危因素的血液系统恶性肿瘤患者,选择allo—HSCT可使部分患者延长无病生存乃至根治。移植前处于CR期者长期生存率明显提高,ALL复发率明显高于AML／MDS。对于急性白血病挽救性治疗争取在取得CR后移植;对于MDS患者一经诊断,无需化疗,可尽早移植。     

Chronic Graft-versus-Host Disease of the Liver Presenting as an Acute Hepatitis following Nonmyeloablative Hematopoietic Stem Cell Transplantation

Chronic graft-versus-host disease (GVHD) of the liver usually presents as an indolent cholestatic disease. We observed 3 patients in whom chronic GVHD of the liver after allogeneic nonmyeloablative hematopoietic stem cell transplantation (HSCT) presented with marked elevations of serum aminotransferases, clinically resembling acute viral hepatitis. The liver biopsies revealed predominant diffuse lobular injury and degenerative small bile ducts. Prompt administration of high-dose immunosuppressive therapy achieved a rapid improvement of liver enzymes and bilirubin levels. We conclude that a distinct syndrome of chronic hepatic GVHD presenting as an acute hepatitis should be considered as one possible explanation for hepatic dysfunction in patients who receive nonmyeloablative allogeneic HSCT.     

Allogeneic hematopoietic stem cell transplantation: complications and results

Acute complications such as veno-occlusive disease of the liver, acute and chronic graft-vs-host disease (GVHD), and infectious conditions remain major obstacles for the success of allogeneic hematopoietic stem cell transplantation (HSCT). Progress in allogeneic HSCT depends on several factors, including the adequate prevention and management of associated complications, advances in the conventional management of diseases currently treated with allogeneic HSCT, expansion of the donor pool, selective control of GVHD, development of more effective preparative regimens to eradicate the neoplastic cell population, characterization of a new generation of hematopoietic growth factors and cytokines, and development of newer techniques for ex vivo manipulation of stem cells. Hematopoietic growth factor-mobilized donor progenitor cells collected from peripheral blood have been shown to be associated with rapid hematopoietic engraftment without an increase in the incidence of acute GVHD compared with allogeneic bone marrow transplantation. Implementation of this approach will enhance donor acceptance, eliminate the risk of general anesthesia, decrease cost, and reduce the risk of infectious complications by reducing the duration of neutropenia. Nonmyeloablative allogeneic stem cell transplantation represents a novel treatment approach that may lead to reduced toxic effects and extended use of this treatment in older patients and in those with malignant and nonmalignant disorders. However, GVHD and disease recurrence remain a challenge. Promising results have been reported in patients with refractory hematologic malignancies and in metastatic renal cell cancer. Because late complications are commonly encountered in patients receiving allogeneic HSCT, lifelong observation is needed.     

改良非清髓性异基因造血干细胞移植治疗SAA疗效观察

目的探讨非清髓性异基因造血干细胞移植(NAST)治疗重型再生障碍性贫血(SAA)的方法及疗效。方法对20例急性SAA患者进行NAST,预处理采用小剂量环磷酰胺、抗淋巴细胞球蛋白或抗胸腺细胞球蛋白;移植后采用环孢菌素、骁悉、抗CD25预防移植物抗宿主病(GVHD)。采用短串联重复序列复合扩增技术检测供者植入情况。结果10例异基因外周血造血干细胞移植患者造血功能获得快速重建;8例脐血造血干细胞移植患者均未植入,但自身造血亦获得安全重建。发生急性GVHD1例,慢性GVHD2例,严重感染性休克、间质性肺炎、败血症各1例均治愈,突发心衰死亡1例,造血重建失败并发感染死亡2例。结论改良NAST疗效肯定、植入率高、并发症少、造血功能恢复快,是治疗SAA的有效方法。     

Peripheral blood vs bone marrow as a source for allogeneic hematopoietic stem cell transplantation.

In this randomized prospective study, we included 30 patients with different hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome or severe aplastic anemia) to compare peripheral blood stem cells (PBSC) (15 patients; mean age 23) and bone marrow (BM) (15 patients; mean age 21.8) as a source for allogeneic transplantation regarding the tempo of hematopoietic recovery and the incidence of acute graft-versus-host disease (GVHD). In the BM group, the median nucleated cell count harvested was 1.3 x 10(10), while in the PBSC group, the aphereses contained a median of 4.4 x 10(6) CD34+/kg recipient weight. PBSC transplantation (PBSCT) was associated with faster hematopoietic reconstitution measured as absolute neutrophil count (ANC) >0.5 x 10(9)/l (log-rank P value <0.0018) and platelet count >25 x 10(9)/l (log-rank P value <0.0098). Seven patients (46.7%) in the BM group vs only one patient (6.7%) in the PBSC group developed acute GVHD (P = 0.013). Therefore, we conclude that PBSCT is associated with faster hematopoietic recovery and the incidence of acute GVHD does not exceed that seen with BMT.     

Treatment of hematological malignancies with nonmyeloablative, HLA-haploidentical bone marrow transplantation and high dose, post-transplantation cyclophosphamide

Hematopoietic stem cell transplantation provides the only potential curative option in many patients with hematological malignancies. Finding a suitably matched donor in a timely manner is often difficult. However, most patients have a partially HLA-mismatched (HLA-haploidentical) first-degree relative readily available. Historically, HLA-haploidentical bone marrow transplantation (BMT) has been considered extremely high risk due to high rates of life-threatening graft-versus-host disease (GVHD) and non-relapse mortality (NRM). Modifications of the stem cell graft, such as T-cell depletion, have resulted in poor rates of engraftment. We have recently completed a phase II clinical trial of nonmyeloablative HLA-haploidentical hematopoietic BMT followed by post-transplantation high-cyclophosphamide. High-dose cyclophosphamide has been shown to create immunogenic tolerance by specifically killing activated mature T-cells. As a result, alloreactive T-cells in the donor graft are selectively destroyed thereby decreasing the incidence of severe GVHD. As well, host-versus-graft reactive T-cells are also selectively eliminated thereby increasing rates of engraftment. Among 210 patients with hematological malignancies receiving nonmyeloablative, HLA-haploidentical BMT with post-transplantation cyclophosphamide, the rate of sustained donor cell engraftment has been 87%. The cumulative incidence of grade 2-4 acute GVHD is 27%, grade 3-4 acute GVHD is 5% and chronic GVHD is 15%. Interestingly, increasing HLA disparity between donor and recipient was not associated with increasing incidence of GVHD or decreased event-free survival. Nonmyeloablative haploidentical stem cell transplantation with post-transplantation cyclophosphamide seems to be a promising, potentially curative, option for patients with hematological malignancies who either lack an HLA-matched related or unrelated donor, or in whom a myeloablative preparative regimen is contraindicated due to significant co-morbidities or history of extensive pre-treatment.     

The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia

We treated 12 patients with chronic myelogenous leukemia (CML) with a low-intensity preparative regimen followed by allogeneic stem cell transplantation in an attempt to confer a curative graft-versus-leukemia (GVL) effect with minimum morbidity. Seven patients in first chronic phase (CP1) and five in second chronic phase (CP2) (age 15-68 years) received a nonmyeloablative conditioning regimen of fludarabine and cyclophosphamide, followed by a G-CSF-mobilized peripheral blood stem cell (PBSC) transplant from an HLA-identical sibling. Cyclosporine (CsA) was used for graft-versus-host disease (GVHD) prophylaxis. Median follow-up was 384 days. Neutrophil recovery occurred at a median of 12 days. There was no transplant-related mortality. Of the seven CP1 patients transplanted, seven achieved a stable molecular remission; two with no post-transplant intervention, three after donor lymphocytes, imatinib and interferon, and two after a myeloablative stem cell transplant. Four of five CP2 patients died in blast crisis and one survived in molecular remission. Of the 12 patients with durable engraftment, six had Grades II-IV acute GVHD; six had limited chronic GVHD. These results suggest that cytoreduction is required to optimize the curative effect of allogeneic stem cell transplantation for CML.     

Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease

Disease-free survival in Philadelphia chromosome-positive ALL (Ph + ALL) is very poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently considered the only procedure with curative potential. To identify factors affecting transplant outcome, we analyzed the data from 197 Ph + ALL patients aged 16 years or older who had undergone allo-HSCT. The 5-year survival rates were 34% for patients in first complete remission (CR), 21% for those in second or subsequent CR, and 9% for those with active disease (P < 0.0001). Multivariate analysis showed four pre-transplant factors as significantly associated with better survival: younger age, CR at the time of transplantation, conditioning with total body irradiation, and HLA-identical sibling donor (P < 0.0001, P < 0.0001, P = 0.0301, P = 0.0412, respectively). Severe acute GVHD increased the risk of treatment-related mortality (TRM) without diminishing the risk of relapse, whereas chronic GVHD reduced the risk of relapse without increasing the risk of TRM. Thus, patients who developed extensive chronic GVHD had better survivals (P = 0.0217), and those who developed grade III-IV acute GVHD had worse survivals (P = 0.0023) than did the others.