移植前及预处理期间肝功能异常对异基因造血干细胞移植效果的影响

 目的 探讨异基因造血干细胞移植(allo-HSCT)患者移植前和预处理期间肝功能异常的特征及其与肝脏合并症和预后的关系。方法 回顾性分析196例allo-HSCT治疗血液系统疾病患者,采集其移植前和预处理期间肝功能数据,观察其对造血重建、移植相关肝脏并发症、生存和移植相关死亡的影响。结果 196例患者中,38例移植前存在肝功能异常,159例预处理期间发生肝功能异常,28例(17.6%)出现3度肝损害,无4度肝损害出现。移植前和预处理期间肝功能异常对造血重建时间、肝静脉阻塞病(HVOD)、肝脏急性移植物抗宿主病(aGVHD)和慢性移植物抗宿主病(cGVHD)发生无显著影响。单因素分析显示年龄(P=0.022)、移植前疾病状态高危(P=0.003)、移植前AST(P=0.019)和TBil水平升高(P=0.015)、Ⅲ~Ⅳ度肝脏aGVHD(P=0.000)和HVOD(P=0.000)是影响总生存(OS)率的危险因素。多因素Cox回归分析显示移植前疾病状态为高危(P=0.002)、Ⅲ~Ⅳ度肝脏aGVHD(P=0.000)是影响OS率的独立危险因素,同时也是影响移植相关死亡(TRM)率的独立危险因素(P值分别为0.002和0.000),而移植前和预处理期间肝功能异常对OS率和TRM率无显著影响。结论 1~2度肝功能异常患者,在密切监测肝功能、充分保肝治疗及积极预防HVOD基础上,可考虑进行allo-HSCT。
        

成人人类白细胞抗原全相合与不相合造血干细胞移植后急性移植物抗宿主病的临床特点与预后

 目的 比较成人人类白细胞抗原(HLA)全相合与HLA不相合异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(aGVHD)的临床特点与疗效。方法 回顾性分析2010年1月至2011年12月于北京大学血液病研究所进行亲缘allo-HSCT患者的临床病历资料,分析不同类型移植后aGVHD的发病类型与特点以及临床疗效的差异。结果 544例患者中,HLA不相合移植后的aGVHD发生率为50.2%,明显高于HLA全相合移植(20.4%,P<0.001),且发生得更早,但Ⅲ°~Ⅳ° aGVHD的累积发生率两组之间差异并无统计学意义(4.5%比6.8%, P=0.066);全相合移植中肠道aGVHD发生率较高(31.1%),而在不相合移植中以皮肤aGVHD为主(66.5%),肠道和肝脏aGVHD发生率均较全相合移植低;全相合移植发生aGVHD时发热患者比例较不相合移植低(28.9% 比47.6%,P=0.028);全相合移植与不相合移植相比,aGVHD总体治愈率低,特别是Ⅲ°~Ⅳ° aGVHD最终疗效差,二线治疗后的完全缓解率低于不相合移植(88.9%比98.8%,P=0.006),aGVHD相关病死率高于不相合移植(11.1%比2.4%,P=0.024)。结论 HLA不相合移植后aGVHD发生率明显高于全相合患者,但重度aGVHD发生率两组间差异无统计学意义,两组患者一线治疗缓解率相近,但HLA不相合移植患者二线治疗后aGVHD总体缓解率更高。     

移植相关的血栓性微血管病的临床观察

目的:了解异基因造血干细胞移植后移植相关血栓性微血管病(TA-TMA)的临床表现、危险因素及预后预测因素。方法:回顾性分析2016年8月—2018年6月期间在广东省人民医院血液科接受异基因造血干细胞移植的76例患者,其中男42例,女34例,中位年龄28岁(范围:12～53岁),基础疾病包括急性髓系白血病42例,急性淋巴细胞白血病22例,慢性粒细胞白血病3例,其他类型血液病9例。临床资料数据采集于住院HIS系统、门诊系统数据记录及电话随访;数据统计采用SPSS分析软件进行分析。结果:76例患者中诊断TA-TMA者23例,非TA-TMA者53例。发生TA-TMA患者的中位年龄为27岁(IQR:20～33岁),中位发病时间为移植后76 d(范围:7～456 d)。对TA-TMA患者的临床症状体征及实验室结果分析表明,与非TA-TMA患者比较,TA-TMA患者的肺动脉高压更加显著(P=0.001),肌酐水平显著升高(P=0.003),尿蛋白明显增多(P=0.024)。单因素分析显示,非血缘供者移植较单倍体移植及同胞全相合移植更容易发生TA-TMA(TA-TMA发生率分别为56.5%、26.1%、17.4%,P=0.015),另外合并Ⅱ～Ⅳ度急性移植物抗宿主病(aGVHD)(P=0.042)、肝功能不全(P=0.026)、严重消化道出血(P=0.001)和重度感染(P0.001)的患者也更易发生TA-TMA。多因素Logistic回归分析显示,重症感染(P=0.002,OR=7.65,95%CI:2.16～27.10)及消化道出血(P=0.015,OR=4.32,95%CI:1.33～14.06)是TA-TMA的危险因素。TA-TMA患者血管性血友病因子(vWF)水平较非TA-TMA患者明显升高(380%±78%vs 288%±104%,P0.001),多因素Logistic回归分析中vWF(P=0.006,OR=1.01,95%CI:1.01～1.02)及蛋白尿(P=0.018,OR=1.91,95%CI:1.12～3.25)也是TA-TMA发生的危险因素,且vWF水平的升高较传统早期预测TA-TMA的生物学指标LDH提前8 d(范围:2～22 d)。合并肝功能损伤或重症感染的TA-TMA患者更易发生死亡事件,P值分别为0.048和0.021。结论:TA-TMA患者临床表现具有非特异性、多样性、复杂性等特点,导致早期诊断困难、治疗预后差。本研究发现无关供者移植及合并Ⅱ～Ⅳ度aGVHD、胃肠道aGVHD、肝功能损伤、胃肠道出血、重症感染、真菌感染的患者更易发生TA-TMA。重症感染、消化道出血、vWF水平、尿蛋白水平升高是TA-TMA发生的危险因素,vWF可能成为TA-TMA早期预测因子。TA-TMA患者的死亡率极高,尤其是合并肝功能损伤或重症感染的患者。本研究能够帮助临床医生早期警惕TA-TMA的发生、早期识别及判断TA-TMA患者预后。     

以提高肾脏病整体预后工作组诊断标准分析脓毒症相关急性肾损伤患者的临床特点

  目的 以提高肾脏病整体预后工作组（KDIGO）诊断标准分析重症监护病房（ICU）内脓毒症相关急性肾损伤（AKI）患者的临床特征和预后。方法 应用KDIGO推荐的AKI诊断标准,收集2007年6月—2012年6月江苏省无锡市人民医院ICU收治的符合入选标准的AKI患者资料,回顾性分析脓毒症相关AKI患者的临床特征、预后和影响患者死亡的主要危险因素。结果 在收治的703例AKI患者中,脓毒症相关AKI 395例（56.2%）,脓毒症是发生AKI最主要的原因。脓毒症相关AKI患者中,AKI Ⅰ期146例（37.0%）,Ⅱ期154例（39.0%）,Ⅲ期95例（24.1%）。与非脓毒症相关AKI患者比较,脓毒症相关AKI组急性生理与慢性健康评分Ⅱ（APACHEⅡ）、序贯器官衰竭评分（SOFA）更高(25.1±4.9比20.5±6.4,12.9±2.6比10.4±4.5;P值均<0.05)。两组基础血肌酐值差异无统计学意义［(82.9±22.2)μmol/L比(83.1±30.0)μmol/L,P>0.05］,但ICU期间脓毒症相关AKI组血肌酐更高［(143.5±21.6)μmol/L比(96.2±15.5) μmol/L,P<0.05］,进展为AKI Ⅱ期和Ⅲ期的比例更高（63.0%比33.1%,P<0.05）,接受肾脏替代治疗的比例更高（22.3%比6.2%,P<0.05）,而肾功能完全恢复的患者比例更少(74.4%比82.8%,P值均<0.05)。脓毒症相关AKI患者90 d病死率高于非脓毒症相关AKI患者(52.2%比34.1%,P<0.05)。随着KDIGO分期的增加,脓毒症相关AKI患者病死率增加。Logistic回归分析显示APACHEⅡ(OR=5.451,95%CI：3.095~9.416)、SOFA(OR=2.166,95%CI：1.964~4.515)和肾脏替代治疗(OR=4.021,95%CI：2.975~6.324)均是脓毒症相关AKI患者死亡的独立危险因素。结论 脓毒症相关AKI 患者全身疾病严重程度高、肾功能差、病死率高。APACHEⅡ、SOFA和肾脏替代治疗是脓毒症相关AKI患者死亡的独立危险因素。        

颅内动脉瘤术后发生大面积脑梗死的危险因素分析

［摘要］　目的　分析颅内动脉瘤术后患者发生大面积脑梗死的危险因素,提高临床医师对该疾病的认识。方法　回顾性分析2010年1月1日至2020年12月31日贺州市人民医院收治的238例颅内动脉瘤患者的临床资料,其中接受介入栓塞治疗131例,开颅夹闭术治疗107例。13例患者术后发生大面积脑梗死（预后不良组）,其余225例患者预后良好（预后良好组）。采用多因素logistic回归分析患者术后发生大面积脑梗死的危险因素。结果　与预后良好组相比,预后不良组世界神经外科联合会（WFNS）分级为Ⅳ～Ⅴ级、改良Fisher分级为Ⅳ级,以及动脉瘤类型为多发动脉瘤（MSA）、不规则颈动脉瘤的人数比例更大;术中动脉瘤夹重新塑型夹闭、临时夹闭和动脉瘤破裂的发生率更高;动脉瘤最大径、大小比更大,差异均有统计学意义（P<0.05）。多因素logistic回归分析结果显示,更大的动脉瘤直径（OR=1.052）和不规则颈部动脉瘤（OR=3.413）是术后发生脑梗死的独立危险因素（P<0.05）。结论　不规则颈动脉瘤和动脉瘤直径大是颅内动脉瘤患者术后发生大面积脑梗死的危险因素,临床医师应对该类患者予以重视,降低术后不良事件发生的风险。     

放射性125I粒子植入治疗非小细胞肺癌近期疗效的多因素分析

  目的 探讨影响放射性¹²⁵I粒子植入治疗非小细胞肺癌（NSCLC）近期疗效的因素。方法 141例原发性NSCLC患者实施CT引导下放射性¹²⁵I粒子植入治疗,其中26例单纯粒子植入,115例粒子植入联合化疗。所有患者术后6个月行胸部CT检查,根据肿瘤大小变化进行疗效评估,并分析影响近期疗效的相关因素。结果 （1）粒子植入后完全缓解37例,部分缓解93例,有效率92.2%。（2）单因素分析显示：肿瘤分型（F=5.162,P=0.023）、覆盖100%肿瘤瘤体剂量（D₁₀₀）（F=100.713,P=0.000）、治疗模式（F=16.205,P=0.000）对局部疗效有影响。单因素logistic回归分析显示：D₁₀₀、治疗模式、肿瘤分型均为影响局部疗效的独立因素。（3）单因素分析显示：肿瘤分型（χ²=7.313,P=0.007）、D₁₀₀（χ²=71.6,P=0.000）、治疗模式（χ²=20.5, P=0.000）均为影响晚期NSCLC粒子植入治疗效果的重要因素。所有患者治疗期间均未发生相关严重并发症,且与近期疗效无明显相关（P>0.05）。结论 CT引导下放射性¹²⁵I粒子植入治疗NSCLC是一种安全、有效的治疗方法,D₁₀₀为影响近期疗效最主要的因素。     

内镜黏膜下剥离术治疗早期食管癌及癌前病变术后延迟性出血的危险因素分析

目的 探讨内镜黏膜下剥离术（ESD）治疗早期食管癌及癌前病变发生术后延迟性出血的可能危险因素。方法 回顾性分析ESD治疗的281例早期食管癌及癌前病变患者的部分临床资料,分别采用单因素分析及多因素非条件Logistic回归分析探讨引起延迟性出血的危险因素。结果 ESD治疗的281例早期食管癌及癌前病变患者中,22例发生延迟性出血,发生率约为7.83％。卡方检验发现,发生延迟性出血组和未发生延迟性出血组在患者年龄构成（P=0.046）、病灶大小构成（P=0.013）、病灶浸润深度构成（P＜0.001）方面差异均有统计学意义。以上3个危险因素连同卡方检验提示P＜0.10的术中出血（P=0.068）经多因素非条件Logistic回归分析后发现,仅病灶浸润深度是早期食管癌及癌前病变ESD术后发生延迟性出血的独立危险因素（P=0.002,OR=6.88,95％CI：1.07～39.28）。结论 年龄≥60岁及直径≥3 cm的早期食管癌及癌前病变患者ESD术后易发延迟性出血,但其直接原因为病灶浸润深度,浸润深度越深越易发生术后延迟性出血。     

血清HIF-1α水平与急性缺血性脑卒中患者静脉溶栓后症状性脑出血发生及预后的关联性研究

［摘要］　目的　分析血清低氧诱导因子-1α（HIF-1α）水平与急性缺血性脑卒中（AIS）患者静脉溶栓后症状性脑出血（sICH）发生及预后的关联性。方法　招募2019年1月至2021年2月中国中医科学院西苑医院收治的AIS患者229例,均在发病4.5 h内接受重组组织型纤溶酶原激活剂（rt-PA）静脉溶栓治疗,以治疗后36 h发生sICH的情况将其分为sICH组（25例）和非sICH组（204例）。使用改良Rankin量表（mRS）评分评估患者治疗后3个月的功能预后情况。采用夹心式酶联免疫吸附试验法测定血清HIF-1α水平。结果　sICH组患者入院时美国国立卫生研究院脑卒中量表（NIHSS）评分、空腹血糖（FBG）和HIF-1α水平均高于非sICH组,且合并糖尿病和既往有脑卒中史的人数比例较非sICH组更高,差异有统计学意义（P<0.05）。受试者工作特征（ROC）曲线分析结果显示,血清HIF-1α水平具有预测AIS患者发生sICH的应用价值［AUC（95%CI）=0.886（0.815～0.957）,P<0.001］,最佳截断值为1.96 ng/ml,其对应的灵敏度和特异度分别为88.0%、78.4%。Cox回归分析结果显示,溶栓前血清HIF-1α≥1.96 ng/ml是AIS患者发生sICH的危险因素（P<0.05）。Spearman秩相关分析结果显示,血清HIF-1α水平与患者治疗后的mRS评分呈正相关（r_s=0.137,P=0.038）。经校正年龄、性别、吸烟史、合并症史等混杂因素后,多元线性逐步回归分析结果显示,血清HIF-1α水平是影响AIS患者治疗后mRS评分的独立因素（t=2.069,β=0.324,P=0.026）。结论　血清HIF-1α水平升高与AIS患者rt-PA静脉溶栓后继发sICH风险增加和短期预后不良有关。     

住院艾滋病患者305例的生存情况及影响因素分析

［摘要］　目的　了解住院艾滋病（AIDS）患者的生存情况及其影响因素,探讨延长AIDS患者生存时间的策略。方法　对2010-01～2012-12住院的305例AIDS患者的临床资料进行回顾性分析,采用COX比例风险模型分析影响生存率的危险因素。结果　截止研究终点,305例患者中,死亡204例（66.9%）,存活101例（33.1%）。第1～3个月的累积生存率分别为45%、25%、11%,中位生存时间为27.4 d。多因素COX比例风险模型分析结果显示,感染途径为性传播和其他途径的死亡风险比静脉吸毒低（HR=0.878,HR=0.373）,基线CD4⁺ T淋巴细胞计数较高者的死亡风险比较低者低（HR=0.157,HR=0.423）,入院时抗病毒治疗者死亡风险较低（HR=0.378）;入院时合并发热者（HR=3.033）、合并AIDS相关性脑病者（HR=1.678）死亡风险较高。结论　AIDS住院患者的住院生存时间相对较短,感染途径、基线CD4⁺ T淋巴细胞计数、入院时是否合并发热、是否合并AIDS相关性脑病,以及是否抗病毒治疗是影响住院生存时间的主要因素。     

70例真菌血症的临床特点分析

  目的 评价北京协和医院真菌血流感染患者病原学及临床特点。方法 回顾性分析北京协和医院2008至2010年真菌血流感染患者的微生物学和临床资料。统计分析采用SPSS17.0软件。结果 本组70例均存在基础疾病和潜在危险因素的患者确诊为真菌血流感染,40例(57.1%)为单数菌感染,30例(42.9%)住院期间合并细菌性血流感染。从70例患者的血培养中共分离122株病原体,72株真菌,50株细菌;念珠菌61株(84.7%),占绝对优势,白念珠菌31株(50.8%),非白念珠菌30株(49.2%)。分析真菌血症的原发感染来源,35例(50.0%)原发真菌血症,18例(25.7%)同时存在下呼吸道定植,10例(14.3%)引起中心静脉导管相关真菌血症,3例（4.3%）继发于腹腔真菌感染,另有4例(5.7%)存在多个部位相同真菌定植。住院期间死亡37例,粗病死率为52.9%,真菌血症所致的直接病死率为32.9%。单因素分析显示,ICU治疗（χ²=15.136,P<0.001）、30 d内手术史（χ²=3.540,P=0.060）、有创机械通气（χ²=4.450,P=0.035）与住院期间死亡相关;住院期间合并细菌性血流感染（χ²=5.657,P=0.017）、循环系统疾病（χ²=3.399,P=0.065）、ICU治疗（χ²=4.955,P=0.026）增加归因病死率。多因素分析中,ICU治疗增加真菌血流感染患者住院期间死亡风险,30 d内手术史与住院期间死亡负相关;ICU治疗和住院期间合并细菌性血流感染增加真菌血症患者的归因病死率。结论 真菌血症多发生于有一定基础疾病的患者,常伴随细菌血流感染。出现真菌血症的患者预后差,半数以上病人死亡,ICU治疗同时增加真菌血流感染的住院期间死亡和归因死亡风险,住院期间合并细菌性血流感染增加归因病死率,30 d内手术史与住院期间死亡负相关。     

Characteristics of late transplant-associated thrombotic microangiopathy in patients who underwent allogeneic hematopoietic stem cell transplantation

Transplant-associated thrombotic microangiopathy (TA-TMA) has a wide range of presentations after hematopoietic stem-cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA-TMA. Among the 1451 HSCT recipients, early TA-TMA occurred in 45 (3.1%) patients at a median of 27 (3-91) days, and late TA-TMA in 39 (2.7%) patients at a median of 303 (122-2595) days. Patients with early TA-TMA were more likely to have high blood calcineurin-inhibitor levels (P < .001) and acute graph-vs-host disease (GVHD, P < .001), while late TMA patients were more likely to have chronic GVHD (P < .001). The estimated median overall survival after onset of TMA for the entire cohort was 6 months. The estimated median overall survival was not reached in patients with an improvement of TMA vs 2 months in patients with no improvement (P < .001). In the early TMA group, older age (for every 10 years, HR 1.40; 95% CI 1.00-1.94; P = .049) and bacterial infection (HR 2.42; 95% CI 0.98-6.00; P = .056) were positively associated with mortality. Switching to MMF treatment (HR 0.40; 95% CI 0.16-0.99; P = .047) and improvement of TMA (HR 0.08; 95% CI 0.03-0.25; P < .001) were negatively associated with mortality in the multivariate analysis. In the late TMA group, the improvement of TMA was the only independent predictor associated with a lower risk of death (HR 0.05; 95% CI 0.02-0.19; P < .001). Mortality rates in both early and late TMA remain unacceptably high. Future studies are needed for early diagnosis, trigger identifications, and use of targeted treatments.     

Prognostic factors and long-term follow-up of basiliximab for steroid-refractory acute graft-versus-host disease: Updated experience from a large-scale study

Acute graft-vs-host disease (aGVHD) is one of the most important causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly for those with steroid-refractory (SR)-aGVHD. We aimed to identify the prognostic factors and long-term clinical outcomes of basiliximab treatment for SR-aGVHD. Basiliximab was administered on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II, or patients showed no response after four doses. Out of 1498 patients receiving allo-HSCT, 230 patients with SR-aGVHD were enrolled. Grade III to IV aGVHD before basiliximab treatment significantly and independently predicted a poorer response to basiliximab in multivariate analysis. And, the cumulative incidence of overall response at 14 days, 28 days, and 56 days after treatment was 41.4% vs 23.1% (P = .023), 70.2% vs 43.6% (P = .002), and 80.1% vs 66.7% (P = .013), respectively. This was for those with grade II and grade III to IV aGVHD. Patients receiving more than four doses of basiliximab had higher rates of infections. The 4-year cumulative incidence of total and severe chronic GVHD after basiliximab treatment was 44.8% (95% CI 38.3%-51.3%) and 2.2% (95% CI 0.3%-4.1%), respectively. The 4-year cumulative incidence of relapse, non-relapse mortality, disease-free survival, and overall survival after basiliximab treatment was 11.3% (95% CI 7.2%-15.4%), 30.0% (95% CI 24.1%-35.9%), 58.7% (95% CI 52.3%-65.1%), and 61.7% (95% CI 55.4%-68.0%), respectively. Comorbidities before allo-HSCT and refined Minnesota aGVHD risk score at diagnosis had significant influences on long-term survival. Thus, basiliximab was a safe and effective treatment for patients with SR-aGVHD.     

Acute megakaryoblastic leukaemia shows high frequency of chromosome 1q aberrations and dismal outcome

Acute megakaryoblastic leukaemia (AMKL) is associated with poor prognosis. Limited information is available on its cytogenetics, molecular genetics and clinical outcome. We performed genetic analyses, evaluated prognostic factors and the value of allogeneic haematopoietic stem cell transplantation (allo-HSCT) in a homogenous adult AMKL patient cohort. We retrospectively analysed 38 adult patients with AMKL (median age: 58 years, range: 21–80). Most received intensive treatment in AML Cooperative Group (AMLCG) trials between 2001 and 2016. Cytogenetic data showed an accumulation of adverse risk markers according to ELN 2017 and an unexpected high frequency of structural aberrations on chromosome arm 1q (33%). Most frequently, mutations occurred in TET2 (23%), TP53 (23%), JAK2 (19%), PTPN11 (19%) and RUNX1 (15%). Complete remission rate in 33 patients receiving intensive chemotherapy was 33% and median overall survival (OS) was 33 weeks (95% CI: 21–45). Patients undergoing allo-HSCT (n = 14) had a superior median OS (68 weeks; 95% CI: 11–126) and relapse-free survival (RFS) of 27 weeks (95% CI: 4–50), although cumulative incidence of relapse after allo-HSCT was high (62%). The prognosis of AMKL is determined by adverse genetic risk factors and therapy resistance. So far allo-HSCT is the only potentially curative treatment option in this dismal AML subgroup.     

Risk factors for and prognosis of hemorrhagic cystitis after allogeneic stem cell transplantation: Retrospective analysis in a single institution

Abstract

Hemorrhagic cystitis (HC) is a major complication after allogeneic stem cell transplantation (allo-SCT) and can be life threatening. To analyze risk factors and prognosis, we retrospectively reviewed 249 cases receiving allo-SCT in our institution. Median age was 47 years (13–72 years). Disease status at SCT was progressive in 73 cases. Conditioning was myeloablative (MAC) in 146 cases. Acute graft-versus-host disease (aGVHD) grade II–IV treated with prednisolone occurred in 82 cases, and cytomegalovirus (CMV) was reactivated in 91 cases. HC was reported in 47 cases at a median of 35 days (7–469 days) after SCT, and 34 (72.3%) cases recovered after a median of 19.5 days (2–252 days). In univariate analysis, the identified risk factors for HC included age over 45 years, progressive disease status, MAC, aGVHD treated with prednisolone, and CMV reactivation. In multivariate analysis, older age, MAC, and CMV remained independent predictors (hazard ratios: 2.35, 3.50, and 2.87). In patients with severe HC, percentage recovery was lower (3 in 13 cases; 23.1%) and the median duration was longer (54 days) than in those with moderate HC (31 in 36 cases; 86.1%, 17 days, P < 0.01). Treatment-related mortality was also higher (59.1%, P = 0.03) and overall survival was poorer (16.7%, P < 0.01) at 1 year after SCT. Prospective studies should be started considering prophylactic antiviral administration in high-risk patients such as those identified in this study.     

异基因造血干细胞移植后单独胃肠道受累急性移植物抗宿主病的临床特征

目的 分析异基因造血干细胞移植(allo-HSCT)后患者发生单独累及胃肠道的急性移植物抗宿主病(aGVHD)的临床特征.方法 回顾性总结2007年11月至2008年12月在我院行allo-HSCT治疗的307例血液病患者的临床资料,分析单独胃肠道受累的aGVHD的临床特征、危险因素、治疗效果及预后.结果 307例患者中174例(56.7%)发生aGVHD,其中单独累及胃肠道的38例,占21.8%.单独累及胃肠道的aGVHD的发生与受者性别、年龄、供受者性别关系、供受者血型关系、基础疾病诊断及回输的单个核细胞均无关;但与移植类型相关,亲缘全相合组发生率高于亲缘不合组及非血缘组.单独累及胃肠道的aGVHD患者经糖皮质激素或抗CD25单克隆抗体治疗,仅有2例死于aGVHD未控制合并感染,总有效率达94.7%;发生Ⅱ～Ⅳ度aGVHD但非单独累及胃肠道的患者抗aGVHD治疗总有效率为85.2%;组间比较差异有统计学意义(P=0.015).单独累及胃肠道的aGVHD中有12例应用抗CD25单克隆抗体治疗,治疗均有效.结论 HSCT后单纯累及胃肠道的aGVHD并不少见,其发生率在亲缘全相合组高于亲缘不全相合组及非血缘组,单独累及胃肠道的aGVHD对抗aGVHD治疗效果好,可能与应用抗CD25单克隆抗体疗效较好有关.     

A complex case of ibrutinib treatment for a CLL patient on haemodialysis

Hypoalbuminaemia has been previously described to predict worse non‐relapse mortality (NRM) and inferior overall survival (OS) in allogeneic haematopoietic cell transplant (allo‐HCT) recipients. Here, we evaluate the role of hypoalbuminaemia (<35 g/l) at time of onset of acute graft‐versus‐host disease (aGVHD) when incorporated into the refined aGVHD score. The study population consisted of 522 patients, median age 53 (18–75) years, who underwent an allo‐HCT mostly for haematological malignancies. Standard risk (SR) aGVHD comprised 467 patients (89%) and the number of high risk (HR) cases was 55 (11%). Median follow‐up for all surviving patients was 26 (3–55) months. Two‐year OS was significantly better in patients with SR aGVHD with a serum albumin ≥35 g/l compared to SR with albumin <35 g/l [70% (95% CI = 64–76%) vs. 49% (95% CI = 42–56%), P < 0·0001]. Also, patients with SR aGVHD and a serum albumin level of ≥35 g/l had a significantly lower NRM at 1‐year post‐transplantation [6% (95% CI = 3–10%) vs. 25% (95% CI = 20–32%), P < 0·0001]. After our findings are validated in a large cohort of patients, we propose that hypoalbuminaemia should be incorporated into the refined aGVHD risk score to further its ability to predict outcomes within this group.     

T cell depletion utilizing CD34(+) stem cell selection and CD3(+) addback from unrelated adult donors in paediatric allogeneic stem cell transplantation recipients

CD34‐selected haploidentical and unrelated donor allogeneic stem cell transplantation (AlloSCT) in paediatric recipients is associated with sustained engraftment and low risk of acute graft‐versus‐host disease (aGVHD), but limited by delayed immune reconstitution and increased risk of viral and fungal infection. The optimal dose of donor T cells to prevent graft failure and minimize risk of early opportunistic infection and post‐transplant lymphoproliferative disorder (PTLD), while avoiding severe aGVHD, remains unknown. We prospectively studied CD34‐selected 8–10/10 human leucocyte antigen (HLA)‐matched unrelated donor (MUD) peripheral blood stem cell transplantation (PBSCT) in a cohort of 19 paediatric AlloSCT recipients with malignant (n = 13) or non‐malignant (n = 6) diseases. T cells were added back to achieve total dose 1·0–2·5 × 10⁵ CD3⁺/kg. GVHD pharmacoprophylaxis consisted only of tacrolimus. All patients engrafted neutrophils. Probabilities of grade II–IV aGVHD, limited chronic GVHD (cGVHD), and extensive cGVHD were 15·8%, 23·3%, and 0%, respectively. One patient developed PTLD. One‐year infection‐related mortality was 5·6%. T cell immune reconstitution was delayed. One‐year overall survival was 82·3%. Five patients with malignant disease ultimately died from progressive disease. CD34‐selected MUD PBSCT using a defined dose of T cell add‐back resulted in high rates of engraftment and low risk of grade II–IV aGVHD, early transplantation‐related mortality, and extensive cGVHD.     

同胞全相合异基因造血干细胞移植治疗95例骨髓增生异常综合征患者的临床分析

 目的 探讨同胞全相合异基因造血干细胞移植(allo-HSCT)治疗骨髓增生异常综合征(MDS)的疗效与时机。方法 回顾分析2003年1月—2012年12月采用同胞全相合allo-HSCT治疗MDS及MDS转急性髓性白血病(AML)95例。采用改良马利兰+环磷酰胺或氟达拉滨的预处理方案,行骨髓和/或外周血干细胞移植。结果 95例患者中93例白细胞植活,Ⅱ~Ⅳ度急性移植物抗宿主病(aGVHD)累计发生率为12.9%±3.5%;慢性移植物抗宿主病(cGVHD) 3年累计发生率为80.3%±4.9%。3年累计复发率(RR)为25.9%±4.7%,非复发死亡率(NRM)为16.1%±4.0%。3年预期总生存(OS)率及无病生存 (DFS) 率分别为69.9%±5.0%和58.0%±5.4%。多因素分析显示,发生Ⅱ~Ⅳ度aGVHD和不发生cGVHD是OS的独立危险因素;国际预后积分系统(IPSS)分组是DFS的独立预后因素。将难治性贫血伴原始细胞增多转化型(RAEB-t)及MDS转AML患者(31例)分为移植前未化疗、化疗未缓解、化疗缓解3组,3年OS率分别为33.9%、32.7%、100.0%,化疗缓解组OS率明显高于另外两组(P<0.05),DFS率、RR率差异无统计学意义。结论 同胞全相合allo-HSCT是治疗MDS的有效手段,IPSS可预测移植后疗效,对于移植前疾病进展的患者,争取缓解后行allo-HSCT可能提高疗效,但尚需进一步临床对照研究。