单倍体移植治疗恶性血液病的临床研究

目的 探讨单倍体移植治疗恶性血液病的疗效.方法 在单倍体移植时采用阿糖胞苷、马利兰、环磷酰胺、甲基环已亚硝脲联合作为预处理方案,用环磷酰胺、重组人粒细胞集落刺激因子、环孢素、麦考酚酸酯、抗胸腺细胞球蛋白、白细胞介素11及甲氨蝶呤联合预防急性移植物抗宿主病（aGVHD）,治疗8例恶性血液病患者.结果 8例患者完全植入,白细胞＞1.0×10^9/L中位时间为16.3 d（＋12～＋20 d）,Ⅲ～Ⅳ度aGVHD的发生率为12.5%,中位随访时间28.8（4-65）个月,无复发,随访至2010年2月仍存活.结论 在单倍体移植治疗恶性血液病时采用阿糖胞苷、马利兰、环磷酰胺、甲基环己亚硝脲联合作为预处理方案,用环磷酰胺、重组人粒细胞集落刺激因子、环孢素、麦考酚酸酯、抗胸腺细胞球蛋白、白细胞介素11及甲氨蝶呤联合预防aGVHD是一种安全、有效的方法.     

异基因造血干细胞移植急性移植物抗宿主病的预防措施

目的 探讨异基因造血干细胞移植（Allo-HSCT）治疗恶性血液病时急性移植物抗宿主病（aGVHD）的预防策略.方法 对15例异基因造血干细胞移植患者联合采用重组人粒细胞集落刺激因子（rhG-CSF）动员,-7 d（回输干细胞前为-,回输后为＋,回输时为0）始环孢素静脉滴注、麦考酚吗乙酯口服;-5～-4 d环磷酰胺静脉滴注,-5 d～-2 d抗胸腺细胞球蛋白静脉滴注;-6 d～＋10 d白细胞介素11（IL-11）皮下注射;＋1 d、＋3 d、＋6 d及＋11 d甲氨蝶呤静脉滴注预防aGVHD.结果 15例患者完全植入,aGVHDⅡ～Ⅳ度的发生率20.0%,Ⅳ度的发生率6.7%,随访中位时间为30.7（4～65）个月,无复发,无恶性血液病存活.结论 异基因造血干细胞移植治疗恶性血液病时联合采用含有rhG-CSF、环孢素、麦考酚吗乙酯、环磷酰胺、抗胸腺细胞球蛋白、IL-11及短程甲氨蝶呤的方案预防aGVHD疗效可靠,值得推广.     

单倍体移植时急性移植物抗宿主病的预防策略

目的探讨单倍体移植时急性移植物抗宿主病（aGVHD）的预防策略。方法采用环磷酰胺于预处理时静脉滴注,重组人粒细胞集落刺激因子（rhG—csr）动员后含有较大剂量CD34‘细胞的供者造血干细胞输注给受者,-7d（回输干细胞前为“-”,回输干细胞后为“＋”）始环孢素A静脉滴注后改为口服维持,-7d始麦考酚酸酯口服;-5d- -2d予抗胸腺细胞球蛋白静脉滴注;-6d～＋10d予白细胞介素-11皮下注射;＋1d、＋3d、＋6d及＋11d予甲氨蝶呤静脉滴注。结果6例患者完全植入,Ⅱ～Ⅳ度aGVHD的发生率50．0％,III～IV度aGVHD的发生率16．7％,随访中位时间为34．7（13—63）个月,无一例复发,至今仍无病存活。结论采用含有环磷酰胺、重组人粒细胞集落刺激因子、环孢素A、麦考酚酸酯、抗胸腺细胞球蛋白、自细胞介素-11及甲氨蝶呤预防急性移植物抗宿主病的方案疗效可值得进一步的探讨及推广。     

脐血移植治疗小儿恶性和非恶性血液疾病的临床研究

目的　探讨脐血移植治疗小儿恶性和非恶性血液病的可行性 ,重点了解造血重建的特点和移植相关并发症的发生情况。方法　用HLA全相合与不全相合的同胞和非血缘脐血移植治疗小儿急性白血病患儿 6例 ,重型 β 地中海贫血 8例 ,再生障碍性贫血患儿 1例。移植的预处理方案HLA全相合同胞与非血缘脐血患儿采用马利兰 +环磷酰胺 +抗胸腺细胞球蛋白方案 ;HLA 2个位点不全相合 β 地中海患儿采用高剂量输血 +去铁胺 +羟基脲 +氟达拉宾 +马利兰 +环磷酰胺 +抗胸腺细胞球蛋白方案。结果　 14例患儿白细胞达到植活标准 ,12例患儿血小板达到植活标准水平 ,其血小板 >5 0× 10 9/L的平均时间为 5 8 6 7d。 13例患儿发生急性移植物抗宿主病 ,其中Ⅰ度aGVHD 9例 ,Ⅱ度aGVHD 3例 ,Ⅳ度aGVHD 1例 ,2例慢性移植物抗宿主病。 9例患儿出现巨细胞病毒感染。 12例患儿长期存活 ;3例分别死于颅内出血、Ⅳ度aGVHD、Ⅲ度出血性膀胱炎。结论　脐血移植可有效治疗小儿恶性和非恶性血液疾病 ;如何有效防治GVHD、病毒与细菌感染等并发症至关重要。     

8例单倍体造血干细胞移植患者急性移植物抗宿主病的护理

<正>随着造血干细胞移植技术的日趋成熟,对于儿童难治性白血病单倍体移植疗效相近于同胞相合移植,父母供儿童子女HLA单倍体造血干细胞移植治疗儿童恶性血液病已经成为一个研究热点~([1])。而急性移植物抗宿主病(acute graft versus host disease,a GVHD)是单倍体造血干细胞移植后的主要相关并发症,a GVHD的有效处理是移植成功的关键,在a GVHD的处理中,作为治疗的配合,护理技术水平的高低起到非常重要的作用,2012年5月—2016年4月笔者所在科15例复发难治性急性淋巴细胞性白血病患者行单倍体造血干细胞移植     

非亲缘异基因骨髓移植治疗恶性血液病的临床研究

目的　评价非亲缘异基因骨髓移植 (allo BMT)治疗恶性血液病的疗效及并发症。方法　予 13例恶性血液病患者非亲缘allo BMT ,预处理方案髓系白血病为改良BUCY ;急性淋巴细胞白血病 (ALL)和合并中枢神经系统白血病 (CNS L)的髓系白血病以全身照射 (TBI) +环磷酰胺 (CTX)为主的化疗。 13例均采用骁悉 (MMF)、CSA加短程MTX联合方案预防移植物抗宿主病 (GVHD)。结果　均较顺利完全预处理及移植治疗。移植后 17d(中位时间 )造血重建。GVHD发生率急性Ⅰ～Ⅲ度 38% ,Ⅲ～Ⅳ度 15 %。随访 2～ 30个月 ,荧光标记STR PCR定量检测 ,75 %患者供体细胞嵌合率(DM) >90 %。 12例非复发状况移植 ,至今存活 9例 ,无白血病生存率 (LFS) 75 %。移植相关死亡率30 %。结论　非亲缘allo BMT能有效地治疗或根治恶性血液病。     

单倍体造血干细胞移植患者出血性膀胱炎的防治策略

目的 探讨单倍体造血干细胞移植出血性膀胱炎的防治策略.方法 回顾性分析对8例恶性血液病患者行单倍体造血干细胞移植时防治出血性膀胱炎的方法及疗效.结果 本组8例中无一例发生早期出血性膀胱炎,2例发生迟发性出血性膀胱炎,其中Ⅰ度1例,Ⅱ度1例,分别发生于＋32 d及＋37 d（回输干细胞后为＂＋＂）.2例患者均有程度不等的尿频、尿急、尿痛症状.检测血清巨细胞病毒IgM均阴性.2例患者经水化、强迫利尿、碱化尿液、阿昔洛韦抗病毒、酚磺乙胺静脉滴注及黄酮哌酯解痉,其中1例输注血小板（患者当时血小板为20×109/L）,经上述处理后症状渐好转至痊愈.结论 充分水化,碱化尿液,加强利尿,使用美司钠及抗病毒药预防及治疗出血性膀胱炎具有明显的疗效.     

单倍体造血干细胞移植患者出血性膀胱炎的防治策略

目的 探讨单倍体造血干细胞移植出血性膀胱炎的防治策略.方法 回顾性分析对8例恶性血液病患者行单倍体造血干细胞移植时防治出血性膀胱炎的方法及疗效.结果 本组8例中无一例发生早期出血性膀胱炎,2例发生迟发性出血性膀胱炎,其中Ⅰ度1例,Ⅱ度1例,分别发生于+32 d及+37 d(回输干细胞后为"+").2例患者均有程度不等的尿频、尿急、尿痛症状.检测血清巨细胞病毒IgM均阴性.2例患者经水化、强迫利尿、碱化尿液、阿昔洛韦抗病毒、酚磺乙胺静脉滴注及黄酮哌酯解痉,其中1例输注血小板(患者当时血小板为20×109/L),经上述处理后症状渐好转至痊愈.结论 充分水化,碱化尿液,加强利尿,使用美司钠及抗病毒药预防及治疗出血性膀胱炎具有明显的疗效.     

单倍体造血干细胞移植患者出血性膀胱炎的防治策略

目的 探讨单倍体造血干细胞移植出血性膀胱炎的防治策略.方法 回顾性分析对8例恶性血液病患者行单倍体造血干细胞移植时防治出血性膀胱炎的方法及疗效.结果 本组8例中无一例发生早期出血性膀胱炎,2例发生迟发性出血性膀胱炎,其中Ⅰ度1例,Ⅱ度1例,分别发生于+32 d及+37 d(回输干细胞后为"+").2例患者均有程度不等的尿频、尿急、尿痛症状.检测血清巨细胞病毒IgM均阴性.2例患者经水化、强迫利尿、碱化尿液、阿昔洛韦抗病毒、酚磺乙胺静脉滴注及黄酮哌酯解痉,其中1例输注血小板(患者当时血小板为20×109/L),经上述处理后症状渐好转至痊愈.结论 充分水化,碱化尿液,加强利尿,使用美司钠及抗病毒药预防及治疗出血性膀胱炎具有明显的疗效.     

异基因骨髓移植和非清髓性干细胞移植嵌合形成过程的比较

目的 研究异基因骨髓移植（allo-BMT）和非清髓性干细胞移植（NST）两种移植方式在供体细胞嵌合状态的形成及转归上的差异，探讨早期供体细胞植入的关键因素。方法 对20例接受allo-BMT和18例NST的患者进行回顾性比较，研究两组患者疾病类型、干细胞来源、预处理方案和移植物抗宿主病预防方案。用复合扩增荧光标记STR-PCR结合毛细管电泳方法对移植后＋7、＋14、＋21d，＋1、＋3、＋6、＋9、＋12个月的嵌合体进行动态检测。结果 （1）NST组在受体年龄、单个核细胞（MNC）、CD34^＋及T细胞数量上均明显高于BMT组，造血重建方面，中性粒细胞绝对值恢复时间与BMT组无差别，但血小板恢复明显早于BMT组。（2）NST组患者供体细胞完全嵌合状态（FDC）的建立比BMT组早（1个月vs 3个月），移植后早期（＋1个月）FDC比例亦明显高于BMT组（38．9％vs 20%），而混合嵌合状态（MC）的发生率明显低于BMT组（61．2％ vs 80％），移植1个月后各时间段两组在嵌合体形成上均无显著性差别。（3）氟达拉滨为基础的NST预处理方案与标准预处理方案相比并未延迟供体细胞的植入。（4）NST组慢性移植物抗宿主病的发生率明显高于BMT组（80％vs 50%，P〈0．01），与NST组输入高剂量的CD34^＋细胞相关。结论 在供体细胞早期植入和嵌合体形成的过程中，移植物中造血干细胞和T细胞数量至关重要，并可能起决定性作用。     

异基因外周血干细胞移植治疗白血病并发症分析及防治

目的探讨不含全身照射（TBI）预处理方案异基因外周血干细胞移植（allo-PBSCT）治疗40例白血病并发症的发生情况及其防治。方法分析我院2001年1月～2008年10月allo-PBSCT治疗的40例患者临床资料。40例的供者均为HLA-Ⅰ/Ⅱ抗原完全相合的同胞,采用不含TBI改良Bu/Cy及减低剂量Bu＋Arac＋CTX＋氟达拉滨（Flu）预处理方案。氨磷汀预防口腔黏膜炎,前列腺素E1预防肝静脉闭塞病（HVOD）;40例均在预处理及移植后造血恢复期应用更昔洛韦预防巨细胞病毒（CMV）感染,采用环胞菌素A和短程MTX进行GVHD的预防。结果40例患者中出现Ⅰ度口腔黏膜炎23例（57.6%）,Ⅱ度口腔黏膜炎4例（10%）。Ⅳ度口腔黏膜炎2例（0.5%）;40例患者中均未发生急性GVHD及急性CMV感染;19例（47.5%）出现慢性GVHD,出血性膀胱炎（HC）发生率0.5%,间质性肺炎（IP）发生率0.25%;40例均未出现肝静脉闭塞病（HVOD）;40例移植患者中5例（12.5%）死于慢性GVHD移植相关并发症。结论预处理及移植后造血恢复期应用更昔洛韦预防CMV感染治疗,可能会减少移植患者CMV感染;使用细胞保护剂氨磷汀可能会减少或减轻移植患者口腔黏膜炎发生;慢性GVHD已日益成为影响异基因外周血干细胞移植后期生命及生活质量的重要因素。     

贵州省首例半相合骨髓移植治疗急性白血病报告

目的 探讨半相合骨髓移植治疗急性白血病的疗效.方法 对1例男性47岁急性髓系白血病M2型患者采用半相合骨髓移植.预处理方案采用改良的BU/CY方案;GVHD的预防采用ATG+CSA+MMF +MTX方案;移植方式采用骨髓加外周血移植.结果 移植后19 d患者造血功能重建.移植后第30天、90天、180天行STR-DNA...     

Pharmacokinetics of mycophenolate mofetil in hematopoietic stem cell transplant recipients

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is increasingly used in the prophylaxis of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HCT). Few pharmacokinetic data are available about the use of MMF for this indication. This case series aimed at analyzing the pharmacokinetics of MMF in a population of HCT recipients representative for everyday practice. From 15 HCT recipients, serial plasma samples were taken after twice-daily oral intake of MMF. Plasma concentrations of total MPA and its glucuronide metabolites, as well as free MPA, were quantified. Median apparent oral MPA clearance (CL/F), apparent half-life, and total MPA area under the curve for hours 0 to 12 (AUC0-12, normalized to 1000 mg MMF) were, respectively, 56 L/h (range: 29-98 L/h), 2.3 hours (range: 0.8-5.7 hours), and 18.0 mg*h/L (range: 10-35 mg*h/L). Total MPA concentrations were below 2 mg/L 8 hours after MMF administration, indicating reduced enterohepatic recirculation. Median free MPA AUC0-12 (normalized to 1000 mg MMF) was 224 microg*h/L (range: 56-411 microg*h/L). Because of high CL/F, total MPA exposure in HCT recipients is low and apparent half-life is short in comparison with reference values from renal transplantation. Exposure may be improved in HCT recipients by higher or more frequent MMF dosing.     

白介素-11对异基因造血干细胞移植治疗复发难治性淋巴瘤血小板恢复的影响

目的：观察白介素-11(IL-11)对异基因造血干细胞移植治疗复发难治性淋巴瘤血小板恢复的影响及其不良反应。方法选取2011年1月—2014年1月应用异基因造血干细胞移植治疗16例复发难治性淋巴瘤,随机分为IL-11治疗组和对症治疗组,对症治疗组仅接受输血小板等对症支持治疗,IL-11治疗组在对症治疗组基础上于移植后7 d起应用IL-112400万U/d,连用14 d,预处理方案为改良BU/CY方案,移植后观察两组患者血小板计数( PLT)恢复至≥20×109/L和≥50×109/L的时间、血小板输注次数及无病生存等情况。结果两组患者均获造血重建,IL-11治疗组移植后PLT恢复至≥20×109/L和≥50×109/L的时间及辐照血小板输注次数均较对症治疗组少(P<0．05)。 IL-11治疗组有2例发生恶心、呕吐、头痛等一过性不良反应,随访至2015年1月,两组患者无病生存率分别为50%和62.5%,差异无统计学意义(P>0．05)。结论异基因造血干细胞移植治疗复发难治性淋巴瘤过程中应用IL-11有加速血小板恢复的作用,IL-11不良反应轻微、耐受性好。     

Psychological and cytokine changes in children and adolescents undergoing hematopoietic stem cell transplantation.

BACKGROUND: Hematopoietic stem cell transplantation is a therapeutic option of a large variety of diseases. It involves several physiological and psychological changes. Investigations of mood changes in patients undergoing hematopoietic stem cell transplantation are common. There are no studies however, on the relationship between changes in mood and physiological changes in hematopoietic stem cell transplantation in children and adolescents. We investigated the correlation between anxiety, depression and serum Interleukin-1beta (IL-1beta), IL-2 and IL-6. METHODS: Participants, 11 boys and 12 girls, aged 6-18 years, were administered the Children Depression Inventory (CDI) and the Spielberger State Anxiety Inventory for Children (SAIC), at four different points in time: at conditioning time when treatment is initiated (time 1 = T1), on the day of hematopoietic transplantation (T2), on the day of engraftment (T3) and a week after the engraftment (T4). At each of those times serum samples for cytokines determination were collected as well. RESULTS: Up to the time of engraftment depression and anxiety were relatively high but resolved subsequently. Globally, there was a significant time effect for anxiety (p = 0.0082). Namely, scores differ between times. Depression showed a similar trend, though this trend did not reach significance (p = 0.1394). Negative correlation was found between serum IL-1beta, IL-2 and IL-6 levels and anxiety (IL-2 and IL-6) and depression scores (IL-1beta and IL-2) at T4. The complex interaction between cytokines, depression and anxiety in children and adolescents undergoing hematopoietic stem cell transplantation merits further long-term studies under natural conditions and on laboratory models.     

Autologous peripheral hematopoietic stem-cell transplantation in a patient with refractory pemphigus

The aim of this study is to explore the effectiveness of autologous peripheral hematopoietic stem-cell transplantation in the treatment of refractory pemphigus. A 35-year-old male patient presented with a 4-year history of recurrent bullae on his trunk and extremities. The diagnosis of pemphigus was made on the basis of the clinical, histologic and immunofluorescence findings. The patient had shown resistance to conventional therapy with glucocorticoid and immunosuppressive agents. Two months before admission, he complained of hip joint pain. X-ray and CT scan revealed aseptic necrosis of the femoral head. Stem-cell mobilization was achieved by treatment with cyclophosphamide, granulocyte colony-stimulating factor (G-CSF) and rituximab. Peripheral blood stem cells were collected via leukapheresis and cryopreserved for later use. Immunoablation was accomplished by using cyclophosphamide (200 mg/kg; divided into 50 mg/kg on days-5,-4,-3, and-2), antithymocyte globulin (ATG; 10 mg/kg; divided into 2.5 mg/kg on days-6,-5,-4, and-3), and rituximab (1200 mg/d; divided into 600 mg/d on days 0 and 7). Autologous peripheral hematopoietic stem cell transplantation was followed by reconstitution of the immune system which was monitored by flow cytometry. The glucocorticoid was withdrawn immediately after transplantation. The pemphigus titer turned negative 6 weeks after transplantation and remained negative. The patient was in complete drug-free remission with no evidence of residual clinical or serological activity of pemphigus during 1 year of follow-up. The patient’s response suggests that autologous peripheral hematopoietic stem cell transplantation may be a potential “cure” for refractory pemphigus. However, further studies are needed to evaluate the risk-benefit ratio of this approach in patients with pemphigus showing resistance to conventional therapy. __________ Translated from Chinese Journal of Dermatology, 2007, 40(1): 13–15 [译自: 中华皮肤科杂志]     

Achievement of target cyclosporine concentrations as a predictor of severe acute graft versus host disease in children undergoing hematopoietic stem cell transplantation and receiving cyclosporine and methotrexate prophylaxis

This study evaluates our institution's target trough cyclosporine (CSA) concentrations as predictors of severe acute graft versus host disease (aGvHD) in children receiving either matched related or unrelated hematopoietic stem cell transplantation (HSCT). The outcomes of 87 consecutive children who underwent allogeneic HSCT and received CSA and methotrexate as prophylaxis against aGvHD between October 1, 1999 and September 30, 2002 were retrospectively evaluated. The proportion of time that each patient maintained a whole blood CSA concentration within or above the initial target range (105-155 ng/mL or 155-210 ng/mL) was calculated for each of the following time periods: in each week after HSCT from day 0 to +28; in the week preceding engraftment; and in the week preceding the onset of aGvHD. Patients were prospectively evaluated twice weekly for the presence and severity of aGvHD by senior attending physicians. The relationship between potential predictors and the development of severe aGvHD was examined using univariate logistic regression. The main variables of interest were the proportion of time that therapeutic or supratherapeutic CSA concentrations were maintained; median CSA concentrations; the number of methotrexate doses received; and the use of folinic acid rescue. Mean follow-up time was 3.0+/-1.9 years among children who survived beyond day +100. Three variables were significantly associated with the development of severe aGvHD on univariate analysis: initial CSA target concentration [odds ratio (OR), 0.24; P=0.03], proportion of time the target CSA concentration was achieved during the second week after transplant (OR, 0.16; P=0.02), and proportion of time the target CSA concentration was achieved during the week before engraftment (OR, 0.22; P=0.0489). Multivariable analysis demonstrated an inverse relationship between the median CSA concentration during the week before engraftment and the development of severe aGvHD (OR, 0.99; P=0.045). These results suggest that achievement of our CSA target concentrations is important to aGvHD outcomes.     

异基因造血干细胞移植治疗儿童血液病

目的探讨异基因造血干细胞移植治疗儿童血液病的价值。方法采用异基因造血干细胞移植治疗11例儿童血液病，其中再生障碍性贫血2例、白血病7例、骨髓异常增生症1例、非霍奇金淋巴瘤1例；预处理采用氟达拉滨／环磷酰胺（FLU／CTX）或全身放疗／环磷酰胺（TBI／CTX），观察患儿的临床治疗效果。结果10例患儿均移植成功，9例患儿生存，其中7例无病存活，存活最长时间为5．5年；CMV感染3例，继发出血性膀胱炎1例，继发弥漫性GVHD1例。结论异基因造血干细胞移植是治疗儿童血液病的有效方法，值得临床进一步推广。