VEN+AZA方案与DAC+预激方案治疗老年复发急性髓系白血病的疗效及安全性

目的 分析维奈托克(VEN)+阿扎胞苷(AZA)方案与地西他滨(DAC)+预激方案治疗老年复发急性髓系白血病的疗效及安全性。方法 根据随机数表法将80例老年复发急性髓系白血病患者分为观察组和对照组各40例。对照组采用DAC+预激方案治疗,观察组采用VEN+AZA方案治疗。比较两组免疫功能(CD3⁺、CD4⁺、CD8⁺及CD4⁺/CD8⁺水平)、功能状态[Karnofsky功能状态(KPS)评分]、血液指标、不良反应发生情况及临床疗效。结果 治疗后28 d,相比对照组,观察组CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺水平和骨髓原始细胞比例及血小板减少发生率、恶心呕吐发生率、感染发生率、低钾血症发生率均较低,KPS评分与白细胞计数、血小板计数和治疗总有效率均较高,差异有统计学意义(P<0.05)。结论 对比DAC+预激方案治疗,采用VEN+AZA方案治疗的效果较...     

地西他滨联合预激方案和传统治疗方案治疗老年MDS/MPD转化的急性髓系白血病的疗效和安全性的比较研究

目的:对地西他滨联合预激方案和传统治疗方案治疗老年骨髓增生异常综合征(MDS)或骨髓增殖性疾病(MPD)转化的急性髓系白血病(AML)的有效性和安全性进行比较研究。方法:回顾性分析28例MDS/MPD转化的老年AML患者的临床资料,分别应用地西他滨联合预激方案11例和传统治疗方案17例(其中"3+7"标准方案8例、CAG方案6例及支持治疗3例),比较分析2组患者的临床疗效及不良反应。结果:地西他滨联合预激组中完全缓解(CR)7例(63.6%),未缓解(NR)4例(36.4%),总有效率(ORR)为63.6%;传统治疗组中CR 4例(23.5%),分别为"3+7"标准方案2例、CAG方案2例,NR 13例(76.5%),ORR为23.5%。地西他滨联合预激组的有效率明显高于传统治疗组,差异有统计学意义(P0.05)。2组患者治疗前骨髓原始细胞数对于缓解与否无差异(P0.05)。2组患者出现的不良反应主要是骨髓抑制、肺部感染、恶心呕吐、肝功能损害和心力衰竭,经过输血和抗感染等支持治疗均可以耐受,2组不良反应发生率比较差异无统计学意义(P0.05)。随访至2013年9月,地西他滨联合预激组和传统治疗组的中位生存分别是15个月和2个月,差异有统计学意义(P0.05)。结论:地西他滨联合预激方案治疗老年转化性AML患者的临床疗效显著,不良反应可以耐受,可作为老年转化性AML的首选方案。     

维奈克拉联合阿扎胞苷加供者淋巴细胞输注治疗髓系肿瘤异基因造血干细胞移植后复发的临床疗效及安全性分析

［摘要］　目的　分析维奈克拉（VEN）联合阿扎胞苷（AZA）加供者淋巴细胞输注治疗髓系肿瘤异基因造血干细胞移植（allo-HSCT）后复发的临床疗效及安全性。方法　回顾性分析2018年9月至2022年6月在广西医科大学第一附属医院接受allo-HSCT后复发,并接受VEN+AZA+供者淋巴细胞输注（DLI）挽救性治疗的8例急性髓系白血病（AML,5例）和骨髓增生异常综合征（MDS,3例）患者的临床资料,评价其治疗效果、并发症及生存状态。结果　8例患者中男女各4例,中位年龄为31（15～64）岁。allo-HSCT后复发的中位时间为316（77～1 099）d,接受VEN+AZA挽救性治疗的中位时间为10（4～25）d,中位疗程为3.5（1～6）个。5例患者接受第1次VEN+AZA+DLI治疗后达到完全缓解（CR）/血细胞计数未完全恢复的完全缓解（CRi）,1例患者在第2疗程联合达雷妥尤单抗治疗后获得CR。2例患者接受首次治疗后仍为未缓解（NR）。中位随访时间为429（40～746）d。8例患者中4例存活（均为首次治疗后即获得并持续CR/CRi的患者）;4例死亡,其中3例因疾病进展死亡［2例为AML,1例为治疗相关性骨髓增生异常综合征（t-MDS）］,1例AML患者因肺部感染导致呼吸衰竭死亡。中位生存时间为429（40～746）d,预计2年总生存率为41.67%。结论　VEN+AZA+DLI治疗allo-HSCT后复发的髓系肿瘤有效,耐受性良好。     

预激CAG方案治疗老年初治急性髓系白血病的临床分析

目的:评价CAG(阿糖胞苷、阿柔比星、粒细胞集落刺激因子)方案治疗老年初治急性髓系白血病(AML)的疗效及不良反应。方法:64例老年初治AML作为观察对象,其中39例患者予以CAG预激方案治疗,完全缓解(CR)后序贯予原方案、HA(高三尖杉酯碱和阿糖胞苷)、DA(柔红霉素和阿糖胞苷)、MA(米托蒽醌、阿糖胞苷)、中剂量阿糖胞苷巩固治疗至少2个循环;25例患者予以标准方案DA或HA方案化学治疗(化疗),CR后序贯予HA或DA、MA、中剂量阿糖胞苷至少2个循环。观察其疗效及不良反应。结果:CAG预激治疗组1个疗程CR 17例,2个疗程CR 6例,总CR率为59%,7例部分缓解(PR),总有效率77%。常规化疗组患者中1个疗程CR 7例,2个疗程CR 4例,总CR率为44%,2例PR,总有效率52%,与CAG预激治疗组相比差异有统计学意义(P<0.05);CAG组的胃肠道反应、感染、出血、脱发、肝功能及肾功能受损、心毒性、骨髓抑制不良反应发生率均明显少于常规化疗组,差异均有统计学意义(均P0.05)。结论:CAG预激方案治疗初治老年AML患者较之传统常规治疗具有有效率高、不良反应较小、患者生活质量高的优点,适合老年AML患者使用。     

Venetoclax联合化疗治疗难治/复发急性髓系白血病8例并文献复习

目的:评价短疗程Venetoclax(VEN)联合小剂量阿糖胞苷(ara-C)方案在难治/复发急性髓系白血病(AML)患者中的疗效和安全性.方法:报告8例以短疗程VEN+小剂量ara-C方案联合治疗的难治/复发AML患者.VEN使用剂量为200～400 mg QD 口服,ara-C 10 mg/m2 Q12 h皮下注射...     

皮下注射小剂量地西他滨联合CHAG预激方案治疗17例复发难治性或老年急性髓系白血病患者的疗效分析

目的:观察小剂量地西他滨皮下注射联合CHAG预激方案(D-CHAG)治疗复发难治性或老年急性髓系白血病(AML)患者的疗效和安全性。方法:回顾性分析17例采用D-CHAG预激方案治疗的复发难治性或老年AML患者的临床资料。结果:接受D-CHAG预激方案治疗的17例患者中,14例完全缓解,3例部分缓解,达完全缓解的中位时间为33(24～45)d。14例完全缓解患者中,微小残留病灶阴性10例,包括初治5例,复发难治5例;微小残留病灶阳性4例,其中3例为难治患者,1例为复发患者。主要不良反应为骨髓抑制及感染,无治疗相关死亡发生。结论:对于老年或复发难治性AML患者,D-CHAG预激方案治疗安全、有效。     

G-CSF预激的小剂量HA方案诱导缓解老年或低增生急性髓细胞白血病的临床研究

目的:探讨初治的老年或低增生性急性髓细胞白血病(AML)患者采用粒细胞集落刺激因子(G-CSF)预激的小剂量高三尖杉酯碱(HHT)和阿糖胞苷(Ara-C)方案(G-HA)诱导缓解的疗效、毒副作用。方法:选择年龄>60岁或低增生AML初治患者共25例,采用G-CSF预激的小剂量HA方案诱导治疗。在化疗的前12h皮下注射G-CSF200μg/m2。治疗过程中,白细胞计数>20×109/L时暂停用,而不停止化疗,待白细胞回落后再继续使用。HHT:1mg/m2,d1～14,每日1次;Ara-C:10mg/m2,d1～14,皮下注射,每12h1次。对完全缓解(CR)者行后期可选择不同标准方案交替巩固化疗,第1年每月1次,第2年每2月1次。结果:第1个疗程后10例患者获得CR,9例获得部分缓解(PR),6例未缓解(NR)。9例PR患者中5例患者经过第2个疗程该方案后取得CR。总有效率76。15例获得CR的患者中11例按计划巩固强化治疗患者未复发,生存期为8～35个月,中位数17个月。有4例复发,经过原方案诱导后1例CR,2例PR,1例死亡。该方案血液学毒性轻,非血液学毒性不明显。结论:初治的老年或低增生性急性髓细胞白血病患者采用G-CSF预激的小剂量HA方案诱导缓解的疗效较好、毒副作用可耐受。     

预激方案治疗老年急性髓系白血病临床观察

目的 评价含粒细胞集落刺激因子(G-CSF)的CAG及CHG预激方案治疗老年急性髓系白血病(AML)的临床疗效及不良反应,并与标准DA方案进行比较分析.方法 选择55例老年AML患者,21例采用CAG预激方案,14例采用CHG预激方案,20例采用标准DA方案化疗.结果 CAG、CHG方案治疗组的CR率和有效率均显著高于常规DA方案治疗.预激方案治疗组骨髓抑制与感染率较常规方案治疗组无明显差异,但严重致死并发症显著低于常规方案治疗(P＜0.05).结论 预激方案化疗效果好、严重毒副反应小,在老年AML患者中值得推荐应用.     

地西他滨及丙戊酸联合预激CAG方案治疗老年急性髓系白血病的临床疗效

目的探讨地西他滨及丙戊酸联合预激CAG方案治疗老年急性髓系白血病(AML)的疗效并分析其影响因素。方法选取老年AML患者方案70例,按照治疗方案的不同分为试验组36例和对照组34例,其中试验组给予丙戊酸、地西他滨+CA(I)G方案[VD-CA(I)G]治疗,对照组给予预激CAG方案治疗,治疗2个疗程后,对比两组临床疗效、生存时间、不良反应,分析影响老年AML患者VD-CA(I)G方案疗效的相关因素。结果试验组完全缓解(CR)率及总缓解率与对照组比较差异无统计学意义(P>0.05)。试验组平均无复发生存(RFS)时间和平均总体生存(OS)时间均显著长于对照组,差异有统计学意义(P<0.05)。Kaplan-Meier生存曲线显示,两组OS时间、无复发生存(RFS)时间比较,差异均有统计学意义(P<0.05)。不同年龄组患者及不同危险度组患者的平均RFS时间、平均OS时间比较,差异均无统计学意义(P>0.05)。所有患者出现骨髓抑制,试验组骨髓抑制期较对照组延长。结论与单独使用CAG方案比较,VD-CA(I)G方案治疗老年AML患者的CR率及总缓解率无明显差别,但是长期生存有益,安全性较好,且该方案的疗效不受年龄、危险度分级的影响。     

阿扎胞苷联合venetoclax治疗新诊断老年急性髓系白血病的临床观察

目的:观察以阿扎胞苷联合venetoclax治疗新诊断老年急性髓系白血病(acute myeloid leukemia,AML)的临床疗效及安全性。方法:回顾性分析上海交通大学医学院附属瑞金医院2018年3月至2020年9月收治的14例新诊断初治、不适合强化疗老年AML患者,阿扎胞苷75 mg/m2第1～7天(d1～7)皮下注射,venetoclax每日口服400 mg d1～28,28 d为1个疗程(首次疗程venetoclax 100 mg d1、200 mg d2、400 mg d3～28口服)。临床观察主要终点为复合完全缓解率[完全缓解(complete remission,CR)+CR伴血细胞不完全恢复(CR with incomplete blood count recovery,CRi)]、总反应率(overall response rate,ORR)、首次到达反应时间及反应持续时间(duration of response,DOR),次要终点为总生存(overall survival,OS)期及药物安全性。结果:14例老年AML患者中位随访时间为12.5(2.0～24.0)个月,CR+CRi率为71%,ORR为79%,中位首次到达反应时间为1.1(1.0～2.1)个月,中位DOR为16.0个月[95%置信区间(confidence interval,CI):4.0～未达到(not reached, NR)],中位OS期为14.0个月(95%CI:2.0～NR);在细胞遗传学中高危的12例患者中,共8例(67%)获CR+CRi,中位DOR为9.0个月(95%CI:2.0～NR),中位OS期为11.0个月(95%CI:2.0～NR);在CR+CRi的10例患者中,至少1次达到微小残留病灶(minimal residual disease, MRD)0.01%有8例(80%),其中位DOR为17.0个月(95%CI:4.0～NR),中位OS期未达到(95%CI:6.0～NR)。所有患者都发生血液系统不同程度的细胞减少,最常见的3级以上不良反应为粒细胞减少(100%),粒细胞减少伴发热6例(43%),血小板减少7例(50%),贫血5例(36%);血液系统以外常见的主要为胃肠道反应,皆为可控的1～2级;1例发生肿瘤溶解综合征;大部分患者耐受。结论:初步结果表明,阿扎胞苷联合venetoclax有效且安全,为不适合强化疗的初治老年AML患者提供了治疗选择。     

地西他滨联合小剂量化疗治疗老年中高危骨髓增生异常综合征及急性髓系白血病的临床观察

目的观察地西他滨联合CAG方案治疗老年中高危MDS及AML的临床疗效及不良反应。方法应用地西他滨联合CAG方案治疗MDS及AML患者10例。1个疗程后评估疗效。结果10例患者,其中3例获得完全缓解（CR）30％,4例为部分缓解（PR）10％,1例获得骨髓缓解（mCR）40％。总有效率为80％。大多数患者出现了可以耐受的不良反应,主要表现为骨髓抑制。结论地西他滨联合CAG方案治疗中高危MDS和老年AML有较好的疗效和安全性。     

CAG方案治疗中高危骨髓增生异常综合征和急性髓系白血病的疗效观察

目的:观察阿糖胞苷、阿克拉霉素和粒细胞集落刺激因子联合方案(CAG方案)治疗中、高危骨髓增生异常综合征(MDS)和老年初治、难治、复发和继发于MDS的急性髓系白血病(AML)的临床疗效及不良反应。方法:应用CAG方案治疗MDS9例和AML23例,完成1个疗程后评估疗效,治疗失败患者则退出观察,有效者继续接受1个疗程治疗。结果:9例MDS临床均有效,其中完全缓解4例(44.4%)。部分缓解3例(33.3%),血液学进步伴骨髓缓解1例(11.1%),骨髓缓解1例(11.1%)。AML临床总有效13例(56.5%),其中完全缓解9例(39.1%),部分缓解4例(17.4%)。大部分患者出现了可以耐受的轻微不良反应,主要表现为骨髓抑制。结论:CAG治疗中、高危MDS和预后差的AML安全有效,长期疗效需进一步观察。     

Addition of cladribine to the standard induction treatment improves outcomes in a subset of elderly acute myeloid leukemia patients. Results of a randomized Polish Adult Leukemia Group (PALG) phase II trial

Intensive induction chemotherapy using anthracycline and cytarabine backbone is considered the most effective upfront therapy in physically fit older patients with acute myeloid leukemia (AML). However, outcomes of the standard induction in elderly AML are inferior to those observed in younger patients, and they are still unsatisfactory. As addition of cladribine to the standard induction therapy is known to improve outcome in younger AML patients. The present randomized phase II study compares efficacy and toxicity of the DAC (daunorubicin plus cytarabine plus cladribine) regimen with the standard DA (daunorubicin plus cytarabine) regimen in the newly diagnosed AML patients over 60 years of age. A total of 171 patients were enrolled in the study (DA, 86; DAC, 85). A trend toward higher complete remission (CR) was observed in the DAC arm compared to the DA arm (44% vs. 34%; P = .19), which did not lead to improved median overall survival, which in the case of the DAC group was 8.6 months compared to in 9.1 months in the DA group (P = .64). However, DAC appeared to be superior in the group of patients aged 60‐65 (CR rate: DAC 51% vs. DA 29%; P = .02). What is more, a subgroup of patients, with good and intermediate karyotypes, benefited from addition of cladribine also in terms of overall survival (P = .02). No differences in hematological and nonhematological toxicity between the DA and DAC regimens were observed.     

Bone Marrow Fibrosis and Early Hematological Response as Predictors of Poor Outcome in Azacitidine Treated High Risk-Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

Azacitidine (AZA) treatment is effective treatment for patients with myeloid disorders, and factors predictive of treatment outcome are under investigation. Little is known about the effect of bone marrow fibrosis on response to AZA therapy. We, retrospectively, evaluated clinical predictors of overall survival (OS) and overall response rate (ORR) for patients treated with AZA in a real-life cohort. We evaluated 94 consecutive patients treated with AZA outside of clinical trials (75 mg/m²/day for 7 days every 28 days; 5 + 2 + 2 schedule), from June 2009 to February 2016. Ninety-three patients were evaluated for response. After a median of 6 cycles, ORR—complete response (CR; including marrow CR) + partial response (PR) + hematological improvement (HI)—was 41.9% (CR = 18.3%; PR = 11.8%; HI = 11.8%). Stable disease was observed in 21.5%, and failure in 36.5%. Pre-AZA bone marrow blast percentage, International Prognostic Scoring System (IPSS) or IPSS-R category, and time from diagnosis to AZA had no effect on response. Median OS from start of therapy was 18.5 months, and was significantly related to higher IPSS category (P = .01), poor cytogenetics according to the IPSS (P = .01), poor and very poor cytogenetics according to the IPSS-R (P = .02), and lower ORR (P = .006). Patients with MF-0 pre-AZA demonstrated significantly higher ORR, (CR + PR + HI) and stable disease, and lower failure rates than those with any grade of fibrosis. Indeed, cases with pre-AZA fibrosis > MF-1 had shorter OS (P = .005). Achievement of HI before 4 cycles of treatment negatively impacted OS (P = .009).     

减低剂量地西他滨治疗输血依赖的骨髓增生异常综合征难治性血细胞减少伴单系病态造血8例疗效分析

目目的 探讨减低剂量地西他滨治疗输血依赖的骨髓增生异常综合征(MDS)-难治性血细胞减少伴单系病态造血(MDS-RCUD)的临床疗效和安全性。方法 评价江苏省血液病研究所2009年11月至2012年5月使用减低剂量地西他滨［20 mg/(m2·d),连续3 d］治疗的8例MDS-RCUD患者的疗效和不良反应。结果 1例(12.5%)获完全缓解,2例脱离成分血输注,3例达血液学改善,总反应率达75.0%。在4例可行细胞遗传学评估的患者中,1例获部分细胞遗传学缓解。Ⅳ级血液学毒性发生率50.0%,Ⅲ～Ⅳ级感染发生率37.5%,无Ⅲ～Ⅳ级出血、严重恶心呕吐(Ⅲ～Ⅳ级)和肝功能损伤(Ⅲ～Ⅳ级)。中位随访时间386.6 d(108~655 d),随访期间无患者死亡。结论 减低剂量地西他滨可以改善MDS-RCUD患者的输血依赖,严重血液学毒性和早期病死率的发生率低。     

Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation

We used the CAG regimen (low-dose cytarabine [10 mg/m2 per 12 hours, days 1-14], aclarubicin [14 mg/m2 per day, days 1-4], and granulocyte colony-stimulating factor [200 micrograms/m2 per day, days 1-14]) for the treatment of patients with primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation (RAEB-T) in addition to relapsed AML. Forty-three of 69 (62%) patients achieved complete remission (CR), including 29 of 35 (83%) patients with relapsed AML, 1 of 8 patients with primary resistant AML, 5 of 8 elderly patients with previously untreated AML, and 8 of 18 patients with previously untreated secondary AML or RAEB-T. Ten of 22 (45%) patients > or = 65 years old achieved CR. The patients who achieved CR received at least 1 course of modified CAG therapy as the first consolidation therapy, followed by various second consolidation and intensification therapies. The median disease-free survival and overall survival were 8 and 15 months, respectively, for relapsed AML; 11 and 8 months for the elderly patients; and 8 and 17 months for secondary AML and RAEB-T. Myelosuppression was mild to moderate, and other than fever, severe nonhematologic toxicity was rare. CAG as the induction therapy seems promising for the treatment of various categories of poor-prognosis AML.     

Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients

Hypomethylating agents (HMA) are currently the only FDA approved therapy for patients with chronic myelomonocytic leukemia (CMML). In the current retrospective study, we assessed response rates as adjudicated by the IWG (International Working Group) MDS (myelodysplastic syndrome) and MDS/MPN myeloproliferative neoplasm overlap syndrome response criteria, in 121 CMML patients treated with Azacitidine (AZA, n = 56) and Decitabine (DAC, n = 65). The overall response rates were 41% by the IWG MDS (AZA- 45%, DAC-39%), and 56% by the IWG MDS/MPN (AZA-56%, DAC-58%) response criteria, with CR (complete remission) rates of <20% for both agents, by both criteria. There were no significant differences in response rates between proliferative and dysplastic CMML. Moreover, 29% of CMML patients in a CR with HMA progressed to AML (blast transformation), underscoring the limited impact of these agents on disease biology. Progression after HMA response was associated with a median overall-survival (OS) of 8 months, while median OS in patients with primary HMA failure was 4 months. Lower serum LDH levels (<250 Units/L) were associated with HMA responses by both criteria; while ASXL1 and TET2 mutational status had no impact. HMA treated patients had a longer median OS (31 vs 18 months; P = .01), in comparison to those treated with conventional care regimens (excluding observation only patients), without any differences between AZA vs DAC (P = .37). In conclusion, this study highlights the inadequacies of HMA therapy in CMML, retrospectively validates the IWG MDS/MPN response criteria and underscores the need for newer, rationally derived therapies.     

Increasing the dose of aclarubicin in low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) can safely and effectively treat relapsed or refractory acute myeloid leukemia

It is difficult for relapsed and refractory acute myeloid leukemia (AML) patients to achieve complete remission (CR). The CAG regimen [low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF)] has been used to treat relapsed and refractory AML patients, and showed good therapeutic efficacy. It is unknown, however, whether increasing the dose of aclarubicin in CAG regimen could treat relapsed or refractory AML safely and effectively. We evaluate the efficacy and tolerability of increasing the dose of aclarubicin in CAG regimen, in 37 relapsed or refractory AML patients. All patients were treated with CAG regimen including low-dose cytarabine (10 mg/m² every 12 h, days 1–14), aclarubicin (5–7 mg/m² every day, days 1–14), and G-CSF (200 μg/m² every day, days 1–14) priming. After a single course of therapy, the overall response [CR + partial remission (PR)] rate of all patients was 78.4 % (29/37), in which the CR rate was 62.2 % (23/37). There was no early death. The median overall survival was 6 months (range 2–36 months). Myelosuppression was ubiquitous, but tolerated. No severe non-hematologic toxicity was observed. Thus, increasing the dose of aclarubicin in CAG regimen can be used safely and effectively in the treatment of relapsed or refractory AML.     

硫唑嘌呤治疗活动性克罗恩病的开放性前瞻性研究

目的 通过长程前瞻性研究观察硫唑嘌呤(AZA)治疗我国活动性克罗恩病(CD)患者的疗效及安全性.方法 收集活动性CD且需使用糖皮质激素治疗者60例,开始予AZA及糖皮质激素治疗,激素撤离后以AZA维持治疗.随访监测第12、24、48、72和96周的临床疗效、内镜下黏膜愈合程度及不良反应.结果 随访第12、24、48、72和96周患者的完全缓解率分别为55.0%、66.7%、61.7%、53.3%和53.3%.25例患者治疗前及治疗48周时行结肠镜检查,8例达到黏膜愈合者随访至第96周时均维持完全缓解(8/8),17例未达黏膜愈合者至第96周时维持完全缓解仅9例(9/17,P=0.026).比较第48周完全缓解组与未完全缓解组的特征,多因素Logistic回归分析显示治疗后超敏C反应蛋白恢复至正常值为AZA有效维持缓解的独立影响因素(OR=10.1,95%CI:1.8～57.9,P=0.09).16例(26.7%)患者发生不良反应,其中10例因不良反应而停药;WBC减少为最常见不良反应(18.3%),发生于用药全程.结论 AZA与糖皮质激素合用可有效诱导活动性CD缓解,AZA可有效维持撤离激素后的长程缓解,AZA最常见的不良反应是WBC减少.部分病例可获得病变肠黏膜愈合,达到黏膜愈合者可维持长程临床缓解.

Abstract：

Objective To evaluate the efficacy and safety of azathioprine (AZA) in long term treatment of patients with active Crohn's disease (CD) in China. Methods Sixty patients with active CD,who needed to be treated with systemic steroids, were recruited. All patients initially received AZA combined with steroids therapy and AZA was maintained for treatment after withdrawal of steroids. Clinical efficacy, endoscopic healing of mucosa and adverse events were assessed at the end of the 12th, 24th, 48th, 72th and 96th weeks. Results The complete remission (CR) of the patients at the 12th, 24th, 48th, 72th and 96th weeks was 55.0%, 66. 7%, 61. 7%, 53. 3% and 53. 3%,respectively. Endoscopic examination was performed in 25 patients before treatment and at the end of the 48th week. Eight of them achieved mucosal healing that was kept to the end of 96th week (8/8).Whereas only 9 out of 17 patients without mucosal healing achieved CR at the end of 96th week (9/17,P=0. 026). The clinical features were compared between CR group and non-CR group at the end of 48th week. Logistic regression analysis showed that regaining of hs-CRP was the only independent factor for maintaining remission by AZA treatment ( P= 0. 009,OR 10.1,95 % CI 1.8 ～ 57.9). Sixteen patients (26.7 % ) had adverse events. Ten (16.7 % ) of them had to halt treatment because of serious adverse events. Leucopenia was the most common adverse event and could be occurred at any time during the treatment. Conclusion AZA combined with steroid therapy can effectively induce remission of active CD. Long term steroid-free remission is also effectively maintained by AZA treatment. The most common adverse event is leucopenia and some patients can get mucosal healing. Those who get mucosal healing may have longer duration of remission.     

Chronic but not acute graft-versus-host disease improves outcome in multiple myeloma patients after non-myeloablative allogeneic transplantation

The outcome of 29 multiple myeloma patients receiving fludarabine and melphalan-based non-myeloablative allogeneic transplant (NMT) was evaluated. Event-free survival (EFS) at 24 months was 33%, being significantly higher for patients who developed chronic graft-versus-host disease (cGVHD) when compared with those who did not [51%vs 0% respectively, P = 0.02; hazard rate = 3.16 (95% confidence interval = 1.09-9.15, P = 0.03)] as well as for patients transplanted in complete remission/partial response (CR/PR) or stable disease (SD), compared with those with refractory/progressive disease (43%vs 0% respectively, P = 0.02). Overall survival (OS) at 24 months was 60%[72%vs 42% for patients who did and did not develop cGVHD respectively (P = 0.1); 63%vs 41% for patients in CR/PR or SD vs refractory/progressive disease at transplant respectively (P = 0.013)]. At a median follow-up of 366 d, 13 patients remained in CR/PR (45% overall response rate). Nine patients have died, three of them as a result of disease progression and six (21%) as a result of transplant-related mortality (TRM). Actuarial incidence of TRM was 37% for patients who developed acute GVHD vs 13% for those who did not (log rank, P = 0.04). The present study suggests that graft-versus-myeloma effect is the main weapon for disease control after NMT in MM patients and the efficacy of this immune effect depends on tumour burden before transplant.