自体造血干细胞移植治疗复发难治性朗格汉斯组织细胞增多症一例并文献复习

目的：探究自体造血干细胞移植（AHSCT）治疗复发难治性朗格汉斯组织细胞增多症（LCH）的疗效。方法报道1例 AHSCT 治疗复发难治性 LCH 患者的治疗经过,并复习相关文献。结果患者经过多次化疗后疗效欠佳,进行 AHSCT 治疗后完全缓解。结论 AHSCT 治疗可作为复发难治性LCH 的有效治疗方案。     

中大剂量阿糖胞苷强化巩固治疗急性髓系白血病15例

 目的　观察中大剂量阿糖胞苷作为急性髓系白血病（AML）缓解后强化治疗方案的临床疗效及其对自体外周造血干细胞采集及造血重建的影响;观察染色体核型分析结果与临床预后的关系。方法　15例AML患者缓解后予中大剂量阿糖胞苷强化治疗;此后有3例患者接受异基因造血干细胞移植（allo-SCT）,7例接受自体外周造血干细胞移植（APBSCT）。结果　2例在CR1期行非血缘allo-SCT,目前均无病生存,1例在复发期行单倍型allo-SCT,在＋110天复发;7例行APBSCT的患者中3例无病生存,另外4例复发;未行移植的5例患者均死亡。7例接受APBSCT的患者采集的中位MNC 7.33×108／kg,中位CD+34细胞6.9×106／kg,中性粒细胞＞0.5×109／L的中位时间＋11天,血小板＞20×109／L的中位时间＋13天。具有预后良好核型的患者3例,2例无病生存;具有预后不良核型的患者4例,2例行allo-SCT,1例行APBSCT,目前均无病生存,另外1例死亡;具有预后中等核型的患者共6例,其中1例联合APBSCT,目前无病生存,其余患者均死亡。结论　中大剂量阿糖胞苷不联合造血干细胞移植作为AML缓解后强化治疗患者复发率较高,具有预后中等和不良染色体核型的患者行allo-SCT可能改善预后;采用中大剂量阿糖胞苷巩固强化治疗的患者均能采集到足够的造血干细胞并能造血重建。     

自体造血干细胞移植治疗恶性血液病61例疗效分析

 目的　评价自体造血干细胞移植（AHSCT）治疗恶性血液病的疗效。方法　中南大学湘雅医院自1994年4月至2008年8月对61例恶性血液病患者进行了61次AHSCT治疗,移植时急性非淋巴细胞白血病（ANLL）30例,非霍奇金淋巴瘤（NHL）25例,霍奇金淋巴瘤（HL）3例,浆细胞瘤3例。ANLL采用预处理方案为MAC方案：美法仑（Mel）160 mg／m2×1次,阿糖胞苷（Ara-C）2.0／2.5 g×2次,环磷酰胺（Cy）1.8 g／m2×2次;淋巴瘤以及浆细胞瘤采用预处理方案：全身放疗（TBI）+Cy,单次照射8～10 Gy,剂量率5 cGy／min,Cy 1.8 g／m2×2次。或在以上方案基础上进行修改。结果　所有患者重建造血,1例患者移植过程中心功能衰竭死亡,移植相关死亡率为1.6 %。60例患者长期随访,1例患者失访。移植组中位随访期为52（2～211）个月,复发13例（21.3 %）,复发中位时间为18（2～77）个月。死亡14例（23.0 %）,现生存47例（77.0 %）,中位生存时间为66（15～211）个月。5年无病生存率（DFS）为[（77.5±5.5）%,比同期单纯接受化疗者的（31.6±7.3）%]明显增高,差异有统计学意义（P＜0.01）。结论　AHSCT移植患者移植相关死亡率低,无病生存率较高,可作为恶性血液病治疗的重要方法。     

联合化疗使成人急性髓系白血病长期无病生存的若干体会

 联合化疗是成人急性髓系白血病（AML）缓解的必要手段，是造血干细胞移植前的重要治疗阶段，大多数患者不具备条件作造血干细胞移植治疗，则要靠联合化疗争取长期无病生存。作者结合长期无病生存的病例，积累30年来临床经验和体会，更多是治疗失败的教训，讨论并分析联合化疗使成人AML长期无病生存的可能性。     

混合谱系白血病-AF6融合基因阳性急性髓系白血病八例临床特点与预后

目的 探讨混合谱系白血病（MLL）-AF6融合基因[t（6;11） （q27;q23）]阳性急性髓系白血病（AML）患者的临床特点与预后.方法 收集安徽省立医院血液内科住院初治MLL-AF6融合基因阳性的AML患者8例,利用多重巢式反转录-聚合酶链反应（RT-PCR）检测治疗前后MLL-AF6融合基因动态变化,分析患者临床特征、免疫表型、细胞遗传学、患者首次诱导治疗后完全缓解（CR）率、总体生存率、造血干细胞移植效果与患者预后的关系.结果 2009年2月至2013年8月住院患者确诊为急性白血病（AL）患者472例,其中AML患者285例,包括MLL-AF6融合基因阳性AML患者8例,占AL的1.69％（8/472）,占AML的2.80％（8/285）.MLL-AF6融合基因阳性AML患者按WHO分型：M11例,M22例,M42例,M53例,以M4/M5为主（5例）.8例AML患者首次化疗后CR 5例,总体生存4例.4例单纯化疗患者中,有2例在第1个疗程结束后MLL-AF6融合基因转阴,且1例获得了血液学CR并已生存26个月,1例初诊后6个月复发,后经治疗后死亡;2例患者第1个疗程结束后MLL-AF6融合基因未转阴（1例转为弱阳性,1例仍为阳性）,均未获得血液学CR且死亡.4例造血干细胞移植患者中,3例移植前MLL-AF6融合基因转阴,均无复发,仍生存,平均生存时间28个月;1例患者移植前MLL-AF6融合基因未转阴（弱阳性）,移植后复发死亡.结论 MLL-AF6融合基因阳性AML患者在AML-M4/M5中发生率高,发病时常伴有高白细胞、器官浸润,且治疗效果差,易复发,预后差,造血干细胞移植可显著改善患者预后.RT-PCR检测治疗前后MLL-AF6融合基因的动态变化可在一定程度上帮助判断患者预后.     

自体造血干细胞移植治疗恶性血液病疗效观察

 目的　观察自体造血干细胞移植（auto-AHSCT）治疗恶性血液病的疗效。方法　1994年10月至2009年5月采用AHSCT治疗的恶性血液病患者28例,中位年龄30（16～45）岁,其中急性髓细胞白血病（AML）19例,急性淋巴细胞白血病（ALL）4例,恶性淋巴瘤（ML）5例。外周血干细胞的动员均给予粒细胞集落刺激因子（G-CSF）5～10 μg／kg。预处理方案主要为美法仑（Mel）140～160 mg／m2+环磷酰胺（CTX）120 mg／kg+阿糖胞苷（Ara-C）2 g／m2。结果　移植相关不良反应低,大部分（26例）患者造血重建快,中性粒细胞（ANC）＞0.5×109／L和Plt＞20×109／L的时间分别为12（8～38）和14（9～128）d,中位随访36（7～68）个月,3年无病存活19例（68 %）,死亡9例（32 %）[其中7例（25 %）死于移植复发,2例（7 %）死于移植后并发症]。结论　AHSCT是一种治疗恶性血液病安全有效的方法。     

减低强度预处理异基因造血干细胞移植治疗老年人复发难治性急性髓系白血病的临床研究

目的 探讨减低强度预处理异基因造血干细胞移植（allo-HSCT）治疗老年人复发难治性急性髓系白血病（AML）的疗效和安全性.方法 采用减低强度预处理的allo-HSCT治疗北京军区总医院2012年1月至2014年1月收治的6例老年人复发难治性AML,其中男5例,女1例,年龄61～68岁,平均年龄64.6岁,供者接受粒细胞集落刺激因子动员,均采用外周血干细胞移植,预处理方案为降低预处理强度的氟达拉滨联合白消安注射液（商品名：白舒非）、阿糖胞苷及环磷酰胺等,移植物抗宿主病（GVHD）预防采用联合免疫抑制剂,移植后3个月进行预防性供者外周血干细胞输注,观察全部患者不良反应、GVHD和无病生存等情况.结果 全部患者获造血重建,中性粒细胞≥0.5×109/L及血小板计数≥20×109/L的平均时间分别为21.5 d及24.2 d,植入证据检测证实为100％为完全供者造血.中位随访18.5个月（5～30个月）,共3例发生GVHD,GVHD死亡1例,复发死亡2例,复发时间为11.5个月（5～ 18个月）,其余3例患者仍无病生存,2年的无病生存率为50％,最长无病生存时间已达30个月.结论 减低强度预处理的allo-HSCT是复发老年人AML挽救性治疗的可行方法.     

T淋巴母细胞淋巴瘤自体干细胞移植后的长期随访观察

目的评价自体造血干细胞移植（autologous hematopoietic stem cell transplantation,AHSCT）治疗复发难治T淋巴母细胞淋巴瘤（TLBL）的临床疗效及安全性。方法本文回顾性分析AHSCT治疗后长期随访的TLBL16例,预处理方案主要为BEAM和BEAC。结果 15例患者可评价疗效,1例失访。中位随访37个月（12~132个月）,中位无进展生存时间（PFS）34.5个月。预计中位总生存时间49月。1、3、5年总生存率分别为60%、53%、32%。初治患者一线治疗有效者,接受AHSCT者预计中位总生存时间为108个月,5年总生存率、无进展生存率分别为62%、63%;复发患者挽救治疗后接受AHSCT者,中位总生存时间为22.8个月,5年总生存率、无进展生存率分别为33%、22%。初始治疗未达CR/PR的难治患者,中位生存仅21个月,5年生存率和无进展生存率分别为20%和29%。结论 AHSCT常规化疗治疗TLBL安全、有效,可提高复发难治的T淋巴母细胞淋巴瘤的远期生存,延长初治TLBL患者的无进展生存期,但复发率仍偏高,值得开展大规模临床试验进一步深入研究。     

FLAG方案治疗难治复发急性髓系白血病13例

 目的　观察FLAG方案治疗难治复发急性髓系白血病（AML）的疗效、骨髓抑制时间以及患者不良反应。方法　氟达拉滨30 mg·m-2·d-1,第1天至第5天;阿糖胞苷2 g·m-2·d-1,第1天至第5天;粒细胞集落刺激因子300 μg／d,第0天至第5天或视具体情况用至中性粒细胞计数（ANC）≥1×109／L。治疗13例（17例次）难治复发AML。其中难治性AML 5例、复发性AML 8例。男9例,女4例。中位年龄41.8（28～67）岁。结果　17例次中11例次有效,6例次完全缓解（CR率35.3 %）,5例次部分缓解（PR率29.4 %）,总有效率64.7 %。CR的患者中有1例已行异基因造血干细胞移植,目前一直处于无病生存状态达8个月。毒副作用主要为骨髓抑制、消化道症状、轻度肝功能异常。中性粒细胞最低时间在开始用药后5～12 d,持续时间7～34 d,血小板最低时间在开始用药后5～13 d,持续时间8～30 d。结论　FLAG方案对难治复发AML有较好疗效,血液学和非血液学毒副作用可以耐受,为患者行造血干细胞移植创造了机会。     

CLAG方案治疗难治复发急性髓系白血病的初步研究

目的观察CLAG方案治疗难治复发急性髓系白血病（AML）的效果和不良反应。方法2014年1月至2015年1月北京隆福医院和协和医院收治的难治复发AML患者12例,均给予1个疗程CLAG方案化疗,观察其疗效和不良反应。结果12例患者,男性6例,女性6例,中位年龄35岁（14～68岁）。按照FAB分型,M1 1例,M28例,M51例,M41例,粒淋混合细胞白血病（HAL）1例。分子遗传学方面,AML1／ETO阳性3例,FLT-ITD突变3例。难治7例,复发5例,既往化疗中位疗程数5个（1～15个）。经CLAG方案1个疗程化疗后,复查骨髓涂片10例（83．33％）患者完全缓解（CR）,1例死亡,1例未缓解。6例有分子遗传学异常者均转为阴性。11例患者均出现骨髓抑制并不同部位感染,3例CR后患者已完成异基因造血干细胞移植。结论CLAG方案对难治复发AML疗效确切,患者耐受性好。一旦获得CR,应该尽快安排异基因造血干细胞移植。     

Randomized controlled study of chemoimmunotherapy of acute myelogenous leukemia (AML) in adults with Nocardia rubra cell-wall skeleton and irradiated allogeneic AML cells

The effect of immunotherapy with Nocardia rubra cell-wall skeleton (N-CWS) on remission duration and survival of adults with acute myelogenous leukemia (AML) was studied in a prospective randomized controlled study. After having been induced into complete remission and having been consolidated, 73 patients were randomized either to maintenance chemotherapy or maintenance chemotherapy plus immunotherapy with N-CWS and irradiated allogeneic AML cells. Thirty-four patients in the chemotherapy group and 32 in the chemoimmunotherapy group were evaluable. Six months after the closure of the study, the immunotherapy showed a borderline beneficial effect on remission duration (P = 0.080) and on survival length (P = 0.098). When the data were analyzed at 30 months after the entry, there was a borderline significant difference in remission duration (P = 0.080) between the two groups, prolonging the 50% remission period by 110 days; but no significant difference in survival length (P = 0.314), although the 50% survival was 168 days longer in the chemoimmunotherapy group. However, there were 4 (18.2%) 5-year relapse-free survivors among 22 patients (11 in each group) who had been diagnosed more than 5 years before the time of the present analysis, and all of them belonged to the chemoimmunotherapy group (P = 0.090). Thus, immunotherapy with N-CWS and irradiated allogeneic AML cells seems to be active in the treatment of adult AML when used for maintenance therapy in combination with chemotherapy.     

Transplantation of non-purified autologous bone marrow in patients with AML in first remission

Four patients with acute myeloid leukemia (AML) were treated with high-dose cyclophosphamide and total body irradiation followed by reinfusion of a portion of their own bone marrow collected during remission. This procedure was applied when the patients were in complete remission. They did not receive further maintenance chemotherapy after grafting. The use of bone marrow for grafting that had been pre-exposed to high-dose chemotherapy for remission induction did not preclude good hematologic regeneration. All patients showed stable remissions that lasted for 64+, 21, 40+, and 19+ months, respectively. Death in the second patient was due to a medullary relapse of the leukemia. Autologous bone marrow transplantation in patients with AML in remission may permit lasting remissions, even when applied without additional chemotherapy and attempts to purify the marrow of neoplastic cells.     

Treatment of acute myeloid leukemias in the adult in relapse

Main chemotherapy regimens used to treat adult patients with acute myeloid leukemia (AML) in first or further relapse were reviewed. In retrospective study, second complete remission rates ranged from 30% to 64%, while they ranged from 8% to 89% in prospective trials. The second complete remission rates were closely associated with age and duration of first complete remission. Combination therapies resulted in higher complete remission rates but were associated with higher toxicity. Median duration of second complete remission was < 14 months and overall median survival was < 12 months. The probability of 3-year survival ranged from 8% to 29%. The inhomogeneity of these studies, the differences in dosages and schedules, and the frequent absence of randomisation make it difficult to select the best salvage therapy. No reinduction regimen has so far clearly proven superior. Only stem cell transplantation provided durable remissions for the majority of AML patients after a first relapse. Considering the poor outcomes of patients with AML in first relapse, improved therapies need to be developed. A number of novel agents that include several differentiation agents, enzyme inhibitors, and monoclonal antibodies have been studied to provide improved outcomes for patients with AML who have relapsed. This is the same for acute promyelocytic leukaemia (APL). Arsenic trioxide has shown great promise for the induction, consolidation, and maintenance of complete remission in relapsed patients with APL. Within this context autologous and allogeneic bone marrow transplantations are also considered in second or subsequent relapse. Molecular monitoring for the PML-RARalpha fusion protein permits prompt intervention for early molecular relapse ultimately improving chances of prolonged remission.     

真实世界遗传学高危的急性髓系白血病患者临床结局分析

目的：观察标准化疗诱导的预后不良组急性髓系白血病（acute myeloid leukemia, AML）的临床特征。方法：回顾性分析南方医科大学珠江医院2016年1月至2020年12月收治的98例首个疗程使用标准方案化疗的预后不良组AML患者的临床和实验室资料。结果：预后不良组AML患者中位年龄为37(18～67)岁,其中男性占61.2%。复杂核型（30.0%）、+8(20.0%)、单体核型（18.9%）是最常见的细胞遗传学异常,FLT3-ITD(34.1%)、ASXL1(20.5%)、RUNX1(15.9%)、DNMT3A(15.9%)、TET2(15.9%)是最常见的基因突变,其首疗程完全缓解率为37.8%。中位总生存期（median overall survival,m OS）和中位无事件生存期（median event-free survival,mEFS）分别是17个月和6个月,中位无复发生存期（median relapse-free survival, mRFS）为12个月。移植方面,有55例患者进行了异基因造血干细胞移植,中位随访16个月,m OS尚未达到,显著高于未移...     

A comparison of bone marrow transplantation with maintenance chemotherapy for patients with acute nonlymphoblastic leukemia in first complete remission

Twenty patients treated with maintenance chemotherapy for acute nonlymphoblastic leukemia after achieving complete remission were compared with 13 patients who underwent bone marrow transplantation from an HLA-identical sibling. The median age was 27 years for both maintenance chemotherapy patients (range 17-42 years) and for patients undergoing bone marrow transplantation (range 16-42 years). The 1-year survival for maintenance chemotherapy was 80% vs. 54% with bone marrow transplantation (p = NS). Complete remission durability was 70% at 1 year for maintenance chemotherapy (34% projected for 5 years) compared with no relapses in the first year with bone marrow transplantation (p = 0.01). Patients on maintenance chemotherapy were hospitalized for an average of 22 days (range 0-171 days) during the first 12 months of treatment. Patients undergoing bone marrow transplantation were hospitalized for an average of 82 days (range 41-113 days) in the same time period. Severe hematologic toxicity was seen in 13/13 bone marrow transplantation patients and 6/20 maintenance chemotherapy patients. Chronic graft-vs.-host disease occurred in 3/7 surviving bone marrow transplantation patients. Maintenance chemotherapy had an average first year cost of +3,076.00 for patients who did not relapse and +48,827.00 for patients that relapsed. The first year costs for bone marrow transplantation averaged +84,102.00. Thus, maintenance chemotherapy was associated with a better early survival, less toxicity, and lower cost than bone marrow transplantation in the first year after initiating therapy. However, fewer relapses with bone marrow transplantation suggest that it will yield a higher long-term survival rate.     

Impact of Time Between Induction Chemotherapy and Complete Remission on Survival Outcomes in Patients With Acute Myeloid Leukemia

BackgroundThe majority of patients with acute myeloid leukemia (AML) receive intensive induction chemotherapy for obtaining a complete remission (CR). Despite consolidation chemotherapy and advances in allogeneic hematopoietic stem cell transplantation, most of these patients finally relapse and die from AML. The aim of this study is to determine the impact of duration of remission achievement on survival of patients with newly diagnosed AML who achieve CR after induction chemotherapy.Materials and MethodsWe retrospectively analyzed patients with AML who received first induction chemotherapy between 2001 and 2018.ResultsThe 5-year overall survival for patients who had early remission after induction chemotherapy and patients who had delayed remission after induction chemotherapy were 83% (95% confidence interval [CI], 0.79-0.87) and 35% (95% CI, 0.31-0.39), respectively (P < .001). The 5-year disease-free survival for patients who had early remission after induction chemotherapy and patients who had delayed remission after induction chemotherapy were 81% (95% CI, 0.75-0.87) and 28% (95% CI, 0.21-0.35), respectively (P < .001).ConclusionIn conclusion, time to entering CR is a predictor factor of overall survival and disease-free survival for patients with newly diagnosed AML who achieve CR after first induction chemotherapy. Patients achieving CR only after a lengthy time (eg, more than 29 days) should be considered to have high relapse rate and should undergo allogeneic hematopoietic stem cell transplantation.     

Autologous hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: treatment outcome and prognostic factor analysis

Objective: The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation(AHSCT) in the treatment of lymphoblastic lymphoma(LL).Methods: We retrospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation(HSCT) from December 1989 to December 2009 in a single institution.Results: HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months(range, 24.6-173.1 months). The 5-year overall survival(OS) and event-free survival(EFS) rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow(BM) involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis.Conclusions: These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission(CR1).     

Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission.

In order to improve leukemia-free survival (LFS) without the treatment-related morbidity of allogeneic bone marrow transplantation or multiple prolonged cycles of consolidation chemotherapy, we evaluated the long-term outcome of autologous transplantation of peripheral blood progenitor cells (PBPCs) as postremission therapy in 129 patients aged 18-71 years (median 49 years) with newly diagnosed acute myelogenous leukemia (AML) in first complete remission (CR1). The median follow-up from remission for surviving patients was 62.2 months (range 3.7-127.9 months). A total of 57 patients were alive and leukemia free at the end of the study. The LFS and overall survival 5 years from remission were 40.2% (+/-9.2%) and 41.4% (+/-9.4%), respectively. The median LFS and overall survival are 17.3 and 23.3 months, respectively. Multivariate analysis identified age as the most significant predictor for both LFS and overall survival. Karyotype was also found to be predictive of outcome. Our results show that autologous transplantation of PBPC procured after a single cycle of high-dose cytarabine-based consolidation chemotherapy for a population of adult patients with AML in CR1 produces a high likelihood of long-term LFS, offering a state of clinical minimal residual disease for the investigation of future therapeutic approaches.     

Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483).

The Eastern Cooperative Oncology Group (ECOG) conducted a prospective phase III study in patients with relapsed/refractory acute myeloid leukemia (AML) to evaluate whether administration of repeated courses of low-dose cytarabine (LDAC) maintenance therapy after induction of complete remission in advanced AML would improve disease-free and overall survival. Patients with AML in second/later relapse or refractory disease were first treated with a combination of high-dose cytarabine and amsacrine. Those who achieved complete remission were then randomized to observation or to receive LDAC, 10 mg/m2 subcutaneously twice a day x2 21 days every 2 months until relapse occurred. Of 86 patients eligible for randomization, 41 patients were assigned to receive LDAC and 45 patients to observation. The median disease-free survival was 7.4 months for patients assigned to LDAC compared to 3.3 months for patients receiving no additional therapy, P= 0.084. The median survival from randomization was 10.9 months and 7.0 months for patients receiving LDAC maintenance chemotherapy and observation, respectively (P= 0.615). The data from this study suggest that LDAC maintenance therapy given to patients with advanced AML who achieve complete remission can increase disease-free survival compared to observation, but does not improve overall survival. Nevertheless, because of the ineffectiveness and toxicity of intensive post-remission chemotherapy in this circumstance, LDAC maintenance therapy, a tolerable outpatient regimen, offers the potential for improved quality of life.     

Hyper-CVAD方案治疗淋巴母细胞淋巴瘤

 目的　观察Hyper-CVAD方案对淋巴母细胞淋巴瘤（LBL）的疗效及其毒副作用。方法　2003年11月至2006年12月收治LBL患者40例,其中20例接受Hyper-CVAD／MA方案交替治疗8个疗程;另20例予常规急性淋巴细胞白血病方案,包括VDCLP、CAT、HD-MTX、EA等方案交替治疗,后予维持治疗。结果　Hyper-CVAD方案组：诱导化疗结束后CR18例（90 ％）,PR2例（10 ％）,总有效率100 ％,3年无病生存率（DFS）55 ％,总体生存率（OS）66 ％。常规急淋方案组：诱导化疗结束后CR17例（85 ％）PR1例（5 ％）,PD2例（10 ％）,总有效率90 ％,3年DFS 35 ％,OS 52 ％。两组患者在诱导期的CR率和有效率差异无统计学意义。3年DFS和3年OS的差异均有统计学意义（P＜0.05）。结论　Hyper-CVAD方案可以提高LBL患者的长期无病生存率,可作为LBL一线治疗方案之一。