Eltrombopag (EPAG) can improve the efficacy of immunosuppressive therapy (IST) consisting of antithymocyte immunoglobulin (ATG) and cyclosporin in severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous usage of EPAG beyond 6 months. Seventy-four treatment-naive Chinese patients with SAA were administrated with rabbit ATG-based IST plus EPAG for 6 months. Patients not achieving complete remission (CR) at 6 months were treated with EPAG for another 6 months. At 1, 3, 6 and 12 months after IST, the cumulative response rates were 31

Addition of eltrombopag (E-PAG) to intensive immunosuppressive therapy (IST) contributes to restoring hematopoiesis in patients with severe aplastic anemia (SAA). Used at relatively low doses in the East Asian population, the efficacies of E-PAG and the predictors for efficacy are not clear. We conducted a retrospective, multicenter study to analyze the efficacy and the possible predicting factors at 6 months in 58 adult SAA patients with rabbit ATG-based IST and E-PAG. The response rate and complete response rate at 6 months were 76% and 21%, respectively. The baseline reticulocyte percentage [area under a curve (AUC)=0.798, 95% confidence interval (CI) 0.640-0.956, P=0.006], absolute reticulocyte count (ARC) (AUC =0.808, 95%CI 0.647-0.970, P=0.004), red cell distribution width – coefficient of variation (RDW-CV) (AUC=0.722, 95%CI 0.494-0.950, P=0.040), and absolute lymphocyte count (ALC) (AUC=0.706, 95%CI 0.522-0.890, P=0.057) were highly predictive of response at 6 months. The tipping values of reticulocyte percentage, ARC, RDW-CV, and ALC were 0.45%, 7.36×109/L, 11.75%, and 1.06×109/L, respectively. The sensitivity and specificity of reticulocyte percentages were 81.6% and 66.7%; ARC were 86.8% and 66.7%, RDW-CV were 94.7% and 55.6%; ALC were 55.3% and 88.9%. At a median follow-up of 15.5 months, the 2-year cumulative overall survival was 92%. The baseline reticulocyte percentage, ARC, RDW-CV, and ALC were potential factors in predicting a favorable effect of rabbit-ATG based IST plus E-PAG in SAA patients of East Asia (ChiCTR2100045895).Clinical Trial Registrationhttp://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, complement-mediated hemolytic anemia caused by a somatic phosphatidylinositol glycan class A (PIGA) gene mutation on the X chromosome of hematopoietic stem cells. The mutation of PIGA gene destroys the biosynthesis of glycosylphosphatidylinositol (GPI), resulting in the lack of GPI anchor proteins, including CD55 and CD59 molecules, in hematopoietic stem cells and their progeny cells (erythrocytes, granulocytes, monocytes, lymphocytes). Erythrocyte membrane without CD55 and CD59 are prone to complement attack and lysis[1]. PNH presents as hemolytic anemia, bone marrow failure, and thrombosis, and so on. Targeting the terminal complement inhibitor, such as eculizumab (C5 inhibitors), could not only control hemolytic anemia, reduce thrombosis and transfusion, improve the staging status of chronic kidney disease, and prevents the deterioration of renal function in PNH patients. However, eculizumab has not yet been available in mainland of China, glucocorticoids is still used as the first-line therapy in China. Methods From September 2020 to April 2022, 26 PNH patients with high disease activity (HAD) were enrolled in the study. Oral prednisone was initiated at a dose of 1mg/kg/day and gradually tapered four weeks later. Clinical characteristics of patients was described in Table 1. Results The hemoglobin paired T-test results before treatment and at 1 month, 3 months, and 6 months after treatment were as follows: (69.12±14.83) vs (77.50±18.11), p＜0.05；(69.12±14.83) vs (74.15±18.23), p=0.15；(69.12±14.83) vs (75.54±19.91), p=0.09; paired chi-square test (McNemar Test) for anemia stratification (>90g/L, 60-90g/L, <60g/L) showed no marked changes: p=0.082, p=0.344, p=0.247; By Friedman Test, it showed reticulocyte percentage was also similar: (6.76±3.92) vs (6.23±4.08) vs (6.62±3.92) vs (7.11±4.73), p=0.457. Before treatment, 25 patients (25/26, 96.15%) were transfusion dependent. After treatment at 1 month, 3 months, 6 months, 19 patients (19/26, 73.08%), 22 patients (22/26, 84.62%), 21 patients (21/26, 80.77%) were transfusion dependent, respectively (p=0.031; p=0.375; p=0.219). Two patients progressed to transfusion dependent at 3 months, 6months, respectively. No patients achieved remission of hemolysis (LDH < 1.5 ⅹULN) at 1, 3, and 6 months; the level of lactate dehydrogenase and indirect bilirubin (IBIL) showed no changes by analysis with Friedman test (p=0.436, p=0.881). By Friedman test, the serum level of D-dimer also showed no changes at different times ( p=0.263). Level of D-dimer elevated (>0.55mg/L) in seven patients before treatment, and returned back within normal range in one patient at 1 month, two patients at 3 months, three patients at 6 months. But among the people with normal D level initially, one patient and three patients each had elevated D-dimer level at 3 months and 6 months, respectively. Two patients achieved renal function improvement at 3 months, 6months, respectively. But three patients had renal function deterioration after treatment. Glomerular filtration rate (GFR) was (114.15±42.98) ml/min/1.73m2 before treatment, and become (117.79±37.69) ml/min/1.73m2, (120.85±44.05) ml/min/1.73m2, (110.30±36.58) ml/min/1.73m2 at 1, 3, and 6 months (p=0.42, p=0.43, p=0.41). Discussion Previous studies have mainly compared the improvement of anemia after breakthrough of PNH by glucocorticoids therapy. The improvement of anemia could not be ruled out as a result of transfusion support or the reduction of temporary hemolysis after breakthrough of PNH. We found the level of LDH increased along with improvement of hemoglobin during prednisone treatment, and percentage of reticulocytes was not changed at same time. It suggested that the improvement of anemia in some patients may not be caused by controlling intravascular hemolysis or the compensatory hyperplasia of the bone marrow, but by transfusion. Conclusions It preliminarily showed prednisone maintenance therapy for PNH could not control hemolysis and thrombosis, and could not improve anemia and renal function. The efficacy of glucocorticoid maintenance therapy in PNH is uncertain. Reference: [1] Brodsky R A. How I Treat Paroxysmal Nocturnal Hemoglobinuria[J]. Blood, 2021, 137(10): 1304-1309. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Background Eltrombopag (EPAG) could improve the efficacy of immunosuppressive therapy (IST) consisted by antithymocyte immunoglobulin (ATG) and cyclosporin (CsA) in untreated severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous use of EPAG beyond 6 months. Methods From February 2018 to October 2021, 92 Chinese patients who were 2 years of age or older with a new diagnosis of acquired SAA and were not eligible for front-line hematopoietic stem-cell transplantation were collected in the China Eastern Cooperation Group for Anemia (CECGA). Patients were treated with rabbit ATG (r-ATG) based IST consisting of CsA. Patients over 12 years old and aging 6-11 years old took EPAG orally at dose of 75mg and 37.5mg once daily, respectively; EPAG was administered with 1.25 mg per kilogram per day for patients with age distribution between 2 and 5 years. Generally, all patients were treated with EPAG at least 6 months. The lack of response at 6 months, relapse, HSCT, development of a clonal hematologic disease including myelodysplastic syndrome, and acute myelogenous leukemia, or disease- or treatment-related death are regarded as events in event free survival (EFS). Results The median age was 38 (2-78) years, with 18 patients (20%) under 18 years old and 21 patients (43%) over 60 years old. In the whole cohort, 61 patients (66%) were diagnosed as SAA and 31 patients (34%) with very severe aplastic anemia (vSAA). At 3, 6 and 12 months, the actuarial overall response rates (ORR) were 55% (51 of 92), 73% (67 of 92) and 81% (60 of 74) and complete response (CR) rates were 11% (10 of 92), 20% (18 of 92) and 34% (25 of 74), respectively. 18 patients (20%) who achieved CR within 6 months were under steady state. In 49 patients with PR at 6 months, 14 (35%) of 40 patients who were continuously exposed to EPAG improved to CR within 6.5 (3 ~ 10) months of median time after 6 months. Among 25 patients who failed at 6 months, 11 patients continued to use EPAG, and 5 patients (45%) improved responses with extended median time of 3 (1 ~ 6) months after 6 months (Figure 1). The cumulative effect curve showed that 93% and 58% of all 12 months remission and CR occurred within 6 months. In patients with PR and NR at 6 months, the better 2-year event free survival (EFS) was found in whom continued to use EPAG (75% vs. 26%, P=0.001) (Figure 2). Discussion EPAG plus IST were used to treat previously untreated SAA patients in prospective studies. The ORR and CR rate at 6 months were 68% ~ 94% and 26% ~ 58%, respectively [1, 2]. We found that 93% of all 12 months remission occurred within 6 months for patients treated with IST and EPAG. It is suggested that EPAG should be used in sufficient dosage at least 6 months. It has been reported that patients with CR and PR were present with better OS of 100% and 92%, while OS of non-responders was 47% (P=0.0016), effect was demonstrated as a predictor for 4-year OS [3]. For patients with PR and NR at 6 months in our study, it was found that not only the response rates, but also the 2-year EFS were improved by continuous usage of EPAG, compared to them discontinued EPAG. In conclusion, additional EPAG to IST mainly take effect within 6 months. Continuous administration of EPAG could improve the hematologic response and EFS in patients without achieving CR at 6 months. REFERENCE [1]. Townsley DM, Scheinberg P, Winkler T, et al., Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med, 2017. 376(16): p. 1540-1550. [2]. Peffault de Latour R, Kulasekararaj A, Iacobelli S, et al., Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. N Engl J Med, 2022. 386(1):11-23. [3]. Assi R, Garcia-Manero G, Ravandi F, et al., Addition of Eltrombopag to Immunosuppressive Therapy in Patients with Newly Diagnosed Aplastic Anemia. Cancer, 2018. 124(21):4192-4201. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

目的 探讨不同减低剂量地西他滨治疗骨髓增生异常综合征(MDS)的临床疗效和安全性.方法 2017年1月至2020年12月于南京医科大学第一附属医院,68例MDS患者前瞻性随机分为2组给予不同减低剂量地西他滨皮下注射,低剂量组:20mg/m2,3d,d1～3;超低剂量组:5～7mg/m2,6d,d1～3,d8,d15,d22;每6周为一个疗程.结果 低剂量组的总反应率(ORR)和血液学改善(HI)均优于超低剂量组(60.0％比24.2％,P=0.003;37.1％比15.2％,P=0.04);两组间完全缓解(CR)、部分缓解(PR)、骨髓完全缓解(mCR)分别为2.9％比3.0％(P=0.966),5.7％比0(P=0.163),14.3％比6.1％(P=0.265).IPSSR分组较低危组和较高危组患者在低剂量组的ORR均优于超低剂量组(60.0％比16.7％,P=0.023;60.0％比28.6％,P=0.043).低剂量组等位基因突变频率(VAF)下降程度高于超低剂量组(15.49％比5.98％,P=0.042).多因素分析显示,地西他滨剂量(OR 0.287,P=0.036),女性(OR 6.855,P=0.002)及 IPSSR 分组(OR 1.222,P=0.043)为影响疗效的相关因素.两组出现Ⅲ～Ⅳ级骨髓抑制(15.2％比25.7％,P=0.280)及感染性发热(36.4％比20.0％,P=0.133)的比例相当,而低剂量组肺部感染比例明显低于超低剂量组(8.6％比33.3％,P=0.012).中位随访时间16个月(2～54个月),两组的转白率(24.2％比20.0％,P=0.673),中位转白时间(5.5个月比6.0个月,P=0.879)及中位生存时间(11个月比11个月,P=0.925)比较差异无统计学意义.结论 地西他滨剂量降至极低水平后疗效不佳,女性患者效果优于男性.

目的 总结输血依赖型非重型再生障碍性贫血(TD-NSAA)患者的临床特点及转归.方法 收集2013年12月至2017年1月就诊于中国贫血东部协作组各医院的124例TD-NSAA患者临床资料,分析临床表现、输血频率、实验室检查结果、并发症、转归及相关因素.结果 共纳入124例TD-NSAA,中位病程38(3～363)个月,中位年龄32(3～80)岁.常见并发症有肝肾功能损害(42例,33.9.％)、糖尿病或糖耐量异常(24例,19.3％)、严重感染(29例,23.4％)、铁超负荷(53/101,52.5％).环孢菌素(CsA)治疗119例,23例有效(19.3％);抗人胸腺细胞免疫球蛋白(ATG)联合CsA治疗30例,17例有效(56.7％)(P＜0.001).57例进展为SAA(46.0％),中位进展时间24(3～216)个月.中性粒细胞绝对值＜0.5x109/L、严重感染和铁超负荷是SAA进展的危险因素(P=0.022,P=0.025,P=0.001).转变为阵发性睡眠性血红蛋白尿症11例、骨髓增生异常综合征2例、急性髓系白血病1例,10例死亡(8.1％).结论 TD-NSAA患者病程迁延,易并发重要脏器功能损伤和疾病进展;CsA治疗效果欠佳,ATG联合CsA强化免疫抑制治疗可能改善预后,值得探索.

目的:分析常见髓系肿瘤基因突变在再生障碍性贫血(AA)中的发生率和特点,与AA患者的临床特征和免疫抑制治疗(IST)结果的相关性.方法:收集213例AA患者初诊及IST后第6、12、24个月的外周血标本,使用二代基因测序法对34种常见髓系肿瘤基因进行检测,分析基因突变特点与AA患者的临床特征、IST疗效及疾病转化之间的相关性.结果:初诊时32例患者检测到基因突变,突变频率为15.02％,18个基因发生总计34次突变.突变次数最多的前3位基因分别为PIGA 35.29％(12/34)、TET2 14.71％(5/34)、ASXL1 11.76％(4/34);儿童组(0～18岁)、青中年组(18～59岁)及老年组(≥60岁)突变率分别为12.50％(4/32)、13.99％(20/143)和21.05％(8/38);重型AA患者突变发生率显著高于非重型AA患者(20.20％ vs 10.53％,P=0.048 7).环孢菌素治疗组突变发生率低于抗人胸腺细胞免疫球蛋白联合环孢菌素治疗组(0 vs 6.9％,P=0.018).治疗新出现预后不良基因突变2例,均无效.结论:AA患者的髓系肿瘤基因突变发生与疾病严重程度和治疗措施可能有关,新出现髓系肿瘤相关基因突变可能与疗效不良有关.

In sight of different pharmacokinetics between races, the recommended dose is 75mg/d for Asian using eltrombopag [1]. However, the efficacy and safety of antithymocyte immunoglobulin (ATG) and cyclosporin A (CsA) with eltrombopag are still largely unknown for adult Asian patients with severe aplastic anemia (SAA).

Abstract Background Large granular lymphocyte leukemia associated pure red cell aplasia (LGLL-PRCA) accounts for a significant portion of secondary PRCA. Cyclosporine (CsA) and cyclophosphamide (CTX) are the main immunosuppressive agents used in treating LGLL-PRCA [1]. Considering the cytotoxicity of CTX, CsA may be proposed as first-line therapy [2]. However, because of the rarity of LGLL-PRCA, long-term responses and relapse rates after CsA and CTX therapy are largely unknown. Methods and results From September 2009 to December 2020, we selected 65 uniformly diagnosed LGLL-PRCA and analyzed clinical features and treatment outcomes of CsA and CTX. In the present study, 43.1% harbored neutropenia (<1.5×10 9/L) and only 1 patient had spondyloarthritis (Table 1). Besides, we found that 9.2% developed recurrent oral ulcer and 18.5% had reduced serum complemet C3 level, both of which were related to abnormal immune status. In our cohort, 44 patients received CsA therapy and 21 patients received CTX therapy. 53.8% (35/65) obtained erythroid lineage response and 26.2% (17/65) achieved complete response. CTX produced higher response rate (81.0% vs 40.9%, P=0.002) and complete response rate (47.6% vs 15.9%, P=0.007) than CsA. We further analyzed related factors influencing efficacy by Binary-Logistic multivariate regression model and found that higher response rate was mainly related to CTX therapy (P=0.02) (Table 2). We detected STAT3 and STAT5b gene in 50 cases. None of the patients had STAT5b mutation and 14 patients had STAT3 mutation. 12 of 14 mutation cases were non-elderly patients (<60 years ). For younger patients, STAT3 mutation was more frequent (85.7% vs 22.2%, P<0.01). In STAT3 mutation group, patients appeared to respond better to CTX than CsA (83.3% vs 37.5%, P=0.138). Up to the last follow-up, 11 patients treated with CsA recurred after CsA reduction or discontinuation, with a median relapse time of 10 (3~80) months after remission. Only 1 patient relpsed after the discontinuation of CTX due to neutropenia and returned to remission status after CTX retreatment. In our research, CsA had higher recurrence rate than CTX without statistical significance (25.0% vs 4.8%, P=0.104). Discussion CsA may be proposed as first-line therapy for LGLL-PRCA [2,3]. CTX also appears to be a good treatment choice, but CTX should not be used for more than 12 months since associated toxicities and the risk for developing myelodysplastic syndromes and acute myeloid leukemia. Therefore, it is necessary to compare the efficacy of CsA or CTX in the treatment of LGLL-PRCA. Deep sequencing analyses of residuals LGLL clones reveals that CTX could eradicate LGLL clones, providing durable response, low relapse rate, whereas CsA is associated with the persistence of leukemic clones, and high frequency of relapse [4]. Our results show that the response rate of CTX is higher than CsA (P=0.02), and the probability of recurrence is relatively low (25.0% vs 4.8%, P=0.104). This is consistent with the results of previous study by Rajala [4]. It was important to note that patients with STAT3 mutations are more likely to respond to MTX [5]. Our study showed that the response rate for CTX was 83.3% in patients with STAT3 mutations, which was seemingly higher than CsA (37.5%), although remained statistically insignificant (P=0.138) that might be due to small number of cases. Conclusions The results of the current study may reflect the real world experience of LGLL-PRCA in whom treated by CTX or CsA, may be limited by its retrospective nature, small cohorts. In preliminary conclusion, LGLL-PRCA could acquired better response to CTX than CsA. Besides, CTX may reduce relapse. References 1. Means RT Jr. Pure red cell aplasia. Blood, 2016, 128(21): 2504~9. 2. Moignet A, Lamy T. Latest Advances in the Diagnosis and Treatment of Large Granular Lymphocytic Leukemia. Am Soc Clin Oncol Educ Book, 2018, 38: 616~25. 3. Go RS, Tefferi A, Li CY, et al. Lymphoproliferative disease of granular T lymphocytes presenting as aplastic anemia. Blood, 2000, 96(10):3644~6. 4. Rajala HLM, Olson T, Clemente MJ, et al. The analysis of clonal diversity and therapy responses using STAT3 mutations as a molecular marker in large granular lymphocytic leukemia. Haematologica, 2015, 100: 91~9. 5. Loughran TP, Zickl L, Olson TL, et al. Immunosuppressive therapy of LGL leukemia: prospective multicenter phase II study by the Eastern Cooperative Oncology Group (E5998). Leukemia, 2015, 29(4): 886~94. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Prospective trials showed the clinical efficacy of eltrombopag in refractory/relapsed aplastic anemia (AA), with up to 40% hematologic improvement [1]. Moreover, eltrombopag was combined with frontline immunosupressive therapy (IST) consisited of antithymocyte immunoglobulin (ATG) and cyclosporin (CsA), with an overall response rate exceeding 80% [2]. The metabolism of eltrodopag is different in disparate population. Currently, the recommended dose is 75 mg/d for East Asian populations [2], Pretreatment clinical and laboratory characteristics predicting eltrombopag response are still unclear in severe AA (SAA) patients of real-world in East Asian.

目的 评估艾曲泊帕联合抗人胸腺细胞免疫球蛋白(ATG)和环孢素(CsA)强化免疫抑制治疗(IST)老年重型再生障碍性贫血(SAA)疗效.方法 收集2017年11月至2020年11月来自连云港市第二人民医院、江苏省人民医院、南京市第二人民医院、浙江省中医院、吉林大学第一医院、北京大学人民医院的35例老年重型再生障碍性贫血患者的临床资料,分析治疗方案、疗效及死亡影响因素.结果 强化免疫抑制治疗单用或联合艾曲泊帕治疗1个月、3个月、6个月、9个月的有效率分别为0％ vs.8.6％(P=0.464),9％vs.47.8％(P=0.03),27.3％ vs.72.7％ (P=0.025),30％vs.79.2％(P=0.002).高龄(≥70岁)和高查尔森指数(≥5分)患者的疗效不佳(60％ vs.40％,P=0.011, 73.3％vs.26.7％,P=0.033).多因素分析发现:使用艾曲泊帕(P=0.012)、中性粒细胞计数(P=0.035)与IST疗效正相关,而年龄(P=0.004)、查尔森合并症指数(P=0.022)与疗效负相关;高查尔森合并症指数(P=0.041)和低中性粒细胞计数(P=0.035)对患者生存不利.结论 对于老年严重型再生障碍性贫血,IST联合艾曲泊帕疗效肯定;高龄(≥70岁)、高查尔森合并症指数(≥5分)以及治疗前粒细胞缺乏症(＜0.5×109/L)患者,疗效较差,生存不佳.

肝炎相关性再生障碍性贫血(HAAA)相对罕见,多发生在急性肝炎后2～3个月[1-2].对于不适合异基因造血干细胞移植(HSCT)的重型再生障碍性贫血(SAA)患者,一线治疗推荐抗人胸腺细胞免疫球蛋白(ATG)联合环孢素(CsA)组成的强化免疫抑制疗法(IST)[3].HAAA发病常常急而重,由于肝功能异常不能耐受HSCT,或缺乏合适供体,需要选择IST.阿伐曲泊帕是一种小分子血小板受体激动剂(TPO-RA),能促进血小板增生,无明显肝脏毒性.我们使用IST联合阿伐曲泊帕治疗2例严重型HAAA,报道如下.

目的 探讨环孢菌素(CsA)治疗成人大颗粒淋巴细胞白血病(LGLL)相关纯红细胞再生障碍(PRCA)患者的疗效,分析疗效相关因素.方法 回顾性分析江苏省人民医院2009年9月至2020年8月间接受CsA治疗的44例成人LGLL相关PRCA患者的临床表现、实验室检查特征及治疗结果,分析疗效相关因素.结果 44例LGLL相关PRCA患者接受CsA治疗;7例完全缓解、11例部分缓解、26例无效;总有效率为40.9％;完全缓解率为15.9％.疗效影响单因素及多因素分析示CsA疗效与STAT3基因突变无显著关联(P=0.691;P=0.688).CsA减量或停药是复发最常见原因(80.0％);环磷酰胺(CTX)对复发LGLL相关PRCA有效率为60.0％.结论 CsA治疗成人LGLL相关PRCA有一定疗效,不受STAT3基因突变阳性影响.最常见复发原因是CsA减量或停药,CTX对复发患者有一定疗效.

目的:探讨阿伐曲泊帕对仑伐替尼相关重型再生障碍性贫血（SAA）的疗效及安全性。方法:回顾性分析南京医科大学第一附属医院收治的1例仑伐替尼相关SAA患者的临床资料。总结治疗过程，分析阿伐曲泊帕治疗结果，并进行文献复习。结果:该例SAA患者肝癌骨转移后使用仑伐替尼和短程局部放疗后出现骨髓衰竭，确诊SAA。应用他克莫司、西罗莫司后血象无改善。接受阿伐曲泊帕40 mg/d治疗4周后，三系造血恢复，脱离输血。结论:阿伐曲泊帕成功治疗1例仑伐替尼相关SAA，耐受性良好，值得临床继续积累相关病例。

目的 评估因肝肾功能异常不耐受强化免疫抑制治疗(IST)联合艾曲泊帕治疗的严重型再生障碍性贫血(SAA)患者,换用阿伐曲泊帕治疗的疗效及耐受性.方法 对2020年10月至2021年7月间江苏省人民医院收治的8例SAA,因肝肾功能异常不耐受IST联合艾曲泊帕,改用阿伐曲泊帕20 mg/d治疗,评估治疗前后血象变化、血栓事件、肝肾功能等指标.结果 阿伐曲泊帕中位治疗时间4(1～6)个月,1例完全缓解,3例部分缓解,2例血红蛋白及血小板改善,1例中性粒细胞及血小板改善,1例患者因治疗时间短未纳入疗效评估.中位起效时间68.5(28～107)d,自身对照显示中性粒细胞计数(P=0.004)、血红蛋白水平(P=0.005)及血小板计数(P=0.016)均较治疗前显著升高.阿伐曲泊帕治疗期间,所有患者无血栓事件发生,肝肾功能指标均维持正常范围内.结论 阿伐曲泊帕对IST联合艾曲泊帕不耐受的SAA患者有一定疗效,耐受性良好.

目的:评估卡泊芬净在预防重型再生障碍性贫血(SAA)患者强化免疫抑制治疗(IST)中侵袭性真菌病(IFD)的效果和安全性.方法:同期对照比较IST后28 d内SAA患者静脉使用卡泊芬净或碳酸氢钠/制霉菌素交替漱口预防IFD的疗效和安全性,未脱离粒细胞缺乏者延长至恢复期,或最多60 d;评估真菌突破感染率、生存率、死亡率等指标.结果:卡泊芬净组纳入45例患者,对照组纳入65例患者.卡泊芬净组真菌感染突破6例(13.3％),明显低于对照组34例(52.3％)(P＜0.001);卡泊芬净组中死于真菌感染0例,对照组中死于真菌感染4例(6.2％)(P=0.009).卡泊芬净组生存率明显优于对照组(95.6％ vs 78.5％,P=0.027).COX回归分析显示,年龄、初诊粒细胞缺乏程度及持续时间是影响生存的不利因素(P＜0.05).卡泊芬净组未见3级及以上卡泊芬净相关毒性.结论:预防性使用卡泊芬净能够降低SAA患者在IST期间IFD的发生率及相关死亡率,且耐受性良好.