成人噬血细胞综合征8例临床分析

目的:探讨噬血细胞综合征（HPS）的病因、临床特点、治疗及预后。方法:对8例噬血细胞综合征的临床资料进行回顾性分析。结果:8例患者原发病以淋巴瘤居多。主要临床表现以持续高热（100%）、肝脾肿大（83%）、出血症状最多,血清LDH显著增高,肝功损害,血清铁蛋白异常增高,甘油三酯增高,三系细胞减少,凝血功能异常、骨髓中可见噬血现象。予以联合化疗、大剂量丙种球蛋白（IVIG）、激素冲击治疗等有一定疗效。死亡7例,存活1例。结论:成人HPS病因多以淋巴瘤为主,临床过程凶险,预后差,死亡率高,联合化疗、大剂量IVIG、激素冲击治疗有一定疗效。     

NK/T细胞淋巴瘤合并噬血细胞综合征1例并文献复习

目的探讨NK/T细胞淋巴瘤合并噬血细胞综合征(HPS)的临床特点及治疗方法。方法回顾性分析佛山复星禅诚医院2021年10月收治的1例NK/T细胞淋巴瘤合并HPS患者的临床资料, 并复习相关文献。结果患者为71岁女性, 因高热入院, 合并重度三系血细胞减少、凝血障碍、铁蛋白升高, 确诊HPS。骨髓活组织检查发现NK/T细胞淋巴瘤骨髓浸润, 发现隐匿的淋巴瘤。治疗过程中出现多重感染等并发症。使用芦可替尼后高热迅速改善, 但凝血功能障碍和血细胞三系减少无改善;采用依托泊苷化疗后血象、凝血功能恢复。结论 HPS可能合并隐匿的淋巴瘤。芦可替尼可以缓解HPS的相关症状, 但不能逆转疾病进程。     

成年人继发性噬血细胞综合征临床特点及预后分析

目的探讨成年人继发性噬血细胞综合征(HPS)的临床特点及预后。方法回顾性分析2014年1月至2020年6月四川省绵阳市中心医院收治的43例初发继发性HPS成年患者的临床资料。总结患者临床表现及生化指标。比较铁蛋白高水平组(≥5 000 μg/L)和低水平组(<5 000 μg/L)间、淋巴瘤相关HPS组与感染相关HPS组间患者的临床特点。采用logistic回归模型进行多因素生存分析。结果患者均以发热为主诉,起病时或治疗中均有感染表现。88.4%(38/43)患者骨髓有噬血现象;88.4%(38/43)患者有不同程度的血细胞减少;36.6%(15/41)患者纤维蛋白原降低[中位值0.93 g/L(0.50~1.35 g/L)];76.7%(33/43)患者氨基转移酶升高。与铁蛋白低水平组(19例)相比,高水平组(21例)单核细胞比例低(0.081±0.040比0.163±0.076,P=0.016),纤维蛋白原降低发生率及氨基转移酶升高发生率均高[60.0%(12/20)比11.1%(2/18),P=0.002;95.2%(20/21)比52.6%(10/19),P=0.006]。与感染相关HPS患者相比,淋巴瘤相关HPS患者淋巴结大发生率高[72.7%(16/22)比27.8% (5/18),χ2=8.021,P=0.005],氨基转移酶升高发生率低[59.1%(13/22)比94.4%(17/18),χ2=4.848,P=0.028]。多因素分析显示,治疗后中性粒细胞比例高(OR=0.886,95%CI 0.786~0.998,P=0.046)及清蛋白水平高(OR=0.376,95%CI 0.156~0.907,P=0.030)是患者生存的保护性因素。结论初发继发性HPS成年患者中,铁蛋白≥5 000 μg/L者单核细胞比例降低,更易出现肝损害及纤维蛋白原降低。淋巴瘤相关HPS患者更易出现淋巴结大,感染相关HPS患者更易出现肝损害。治疗后中性粒细胞比例低、低蛋白血症提示继发性HPS成年患者预后较差。     

以噬血细胞综合征起病的组织细胞坏死性淋巴结炎1例并文献复习

目的探讨组织细胞坏死性淋巴结炎(HNL)合并噬血细胞综合征(HPS)的诊断及治疗。方法总结中国医学科学院血液病医院2019年3月收治的1例HNL合并HPS患者的临床特征、诊治经过以及疗效, 并进行文献复习。结果患者, 女性, 17岁, 以发热伴双侧颈部淋巴结肿大为首发症状, 伴咳嗽、咳痰。入院后疾病迅速进展, 血清铁蛋白进行性升高, 采用激素+依托泊苷治疗病情控制后, 经骨髓涂片发现不典型淋巴细胞及噬血现象, 淋巴结活组织检查示HNL病理特征, 综合诊断为HNL合并HPS。出院后随访3个月时患者病情稳定。结论 HNL合并HPS患者临床表现与其他血液系统恶性疾病具有相似性, 采取多种手段联合能够提高疾病的早期诊断率。在患者血清铁蛋白进行性上升时, 及时应用激素治疗, 必要时联合依托泊苷, 能够迅速控制病情进展。     

成年人Still病合并噬血细胞综合征二例并文献复习

 目的　探讨成年人Still病（AOSD）合并噬血细胞综合征（HPS）的诊断及治疗。方法　报道2例AOSD合并HPS的病例并进行相关文献复习。结果　2例AOSD合并HPS患者经早期诊断及有效治疗后疾病缓解并长期生存。结论　AOSD患者治疗过程中出现不明原因的病情加重,且伴有一系和多系血细胞减少、血清铁蛋白明显升高或高三酰甘油血症时,需考虑合并HPS可能,早期完善骨髓细胞学检查,有助于诊断。氟达拉滨用于AOSD相关HPS的治疗具有较好的安全性,可能迅速控制疾病进展。     

成年人疑似原发性噬血细胞综合征合并侵袭性自然杀伤细胞白血病一例并文献复习

目的:提高对成年人原发性噬血细胞综合征（HPS）合并侵袭性自然杀伤细胞白血病（ANKL）的认识。方法:回顾性分析南方医科大学南方医院惠桥医疗中心2017年10月收治的1例疑似原发性HPS合并ANKL成年病例的临床资料，并复习国内外相关文献。结果:患者，男性，21岁，持续发热，血细胞减少，脾大，纤维蛋白原低，铁蛋白显著升高，骨髓存在噬血细胞，自然杀伤（NK）细胞活性减低，可溶性CD25升高，流式细胞术检测NK细胞表达异常，存在家族性溶酶体转运调节因子（LYST）、UNC13D基因缺陷，疑似原发性HPS合并ANKL。给予4个疗程EPOCH+PEG-Asp（依托泊苷、地塞米松、长春地辛、环磷酰胺、多柔比星脂质体、培门冬酶）方案化疗，西达苯胺20 mg、2次/周维持治疗，无关全相合造血干细胞移植。随访35个月，疾病持续缓解。结论:成年人HPS即使存在继发性病因，仍有必要行相关基因筛查以避免误诊。HPS合并ANKL患者病情进展迅速，早期病死率高，确诊后宜尽早采用EPOCH+PEG-Asp方案诱导治疗及异基因造血干细胞移植。     

成年人噬血细胞综合征四例并文献复习

 目的　研究成年人噬血细胞综合征（HPS）的临床特征、国际最新HPS-04治疗方案及其与预后的关系。方法　回顾性分析经临床特征、骨髓穿刺结果证实的4例成年HPS患者的治疗经过和临床效果。结果　4例成年HPS患者虽经积极规范治疗,但皆病情恶化。结论　HPS患者病情凶险,进展快,应提高警觉,争取较好疗效。     

以骨髓坏死及噬血细胞综合征为首发表现的费城染色体阳性成年人急性淋巴细胞白血病1例并文献复习

目的探讨以骨髓坏死及噬血细胞综合征(HPS)为首发表现的费城染色体阳性(Ph+)成年人急性淋巴细胞白血病(ALL)的临床特点及治疗情况。方法回顾性分析2019年5月北京友谊医院收治的1例以骨髓坏死及HPS为首发表现的Ph+ ALL成年患者的临床资料, 并复习相关文献。结果患者, 男性, 58岁。以骨髓坏死及HPS为首发表现, 给予HPS一线治疗后骨髓坏死缓解, 后诊断为Ph+ ALL。HPS病情稳定后进行ALL的标准治疗, HPS未再反复, 患者拒绝接受异基因造血干细胞移植。最终因合并重症肺炎及消化道出血死亡, 但患者生存期明显延长。结论以骨髓坏死为首发表现的HPS原发病需警惕ALL可能, 对于合并HPS的ALL患者需首先应用针对HPS的一线治疗方案, HPS病情稳定后需及时回归到ALL的治疗中来。     

EB病毒编码的小RNA检测在噬血细胞综合征骨髓活检中的意义

 目的　探讨噬血细胞综合征骨髓活检样本病理改变特点及与EB病毒（EBV）感染的关系,以及EBV编码的小RNA（EBER）检测技术在噬血细胞综合征骨髓样本检测中的价值。方法　应用HE、免疫组织化学EnVision二步法、EBER原位杂交技术,观察51例噬血细胞综合征患者骨髓活检样本形态学改变及噬血现象,并检测EBV潜在膜蛋白1（LMP-1）、EBER及其他相关标志。结果　51例噬血细胞综合征患者中,49.0 %（25／51）可见骨髓腔内造血细胞丰富,27.5 %（14／51）各系造血细胞增生情况与本年龄段相符,23.5 %（12／51）造血细胞减少和分布稀疏,较相同年龄患者应有的骨髓造血细胞减少明显。43.1 %（22／51）可以见到噬血现象。91.4 %（32／35）见增生细胞表达CD68／KP-1,89.5 %（17／19）增生细胞表达CD68／PG-M1,提示单核细胞增生明显。所有病例进行EBER检测,51.0 %（26／51）阳性,41例同时进行LMP-1和EBER检测,其中46.3 %（19／41）EBER阳性,而LMP-1全部阴性（Fisher精确概率法,P＝0.000）。结论　噬血细胞综合征患者骨髓活检组织可以见到造血细胞增生减低及噬血现象。病理形态学的噬血现象有时较难判定,借助于免疫组织化学检测组织细胞的增生很有意义。同时,采用EBER检测EBV对诊断的意义大于检测LMP-1。     

噬血细胞综合征102例临床观察及预后分析

目的 探讨噬血细胞综合征（HPS）的临床特征与预后的关系.方法 对2011年1月至2014年6月确诊的102例HPS患者的病因、临床表现、实验室检查及治疗进行回顾性分析.结果 102例患者中,肿瘤相关性HPS最多见,共42例（41.18％）.噬血细胞综合征2004诊断标准中各指标符合率分别为：发热100％（102例）,脾大79.41％（81例）,两系或三系血细胞减少81.37％（83例）,高三酰甘油血症38.24％（39例）,低纤维蛋白原血症53.92％（55例）,铁蛋白升高99.02％（101例）,骨髓噬血现象76.60％（72例）.用Cox单因素分析显示,患者年龄、性别、血小板计数、清蛋白水平与预后有关,差异有统计学意义（P＜0.05）.多因素生存分析显示,患者年龄、血小板计数、清蛋白水平与预后有关,差异有统计学意义（P＜0.05）.结论 HPS可由多种病因所致,肿瘤相关性多见,临床表现多样,发病年龄、血小板计数、清蛋白水平是影响预后的独立危险因素.     

鼻腔及鼻咽部恶性淋巴瘤60例临床病理观察

 报告鼻腔及鼻咽部恶性淋巴瘤60例，其中属中线恶组（MMH）41例，其中24例作免疫组化，证实为T细胞型淋巴瘤；中线非何杰金氏淋巴瘤（MNHL）19例，其中10例作免疫组化，证实为T细胞型4例，B细胞型6例。MMH与MNHL对比观察，前组有肉芽组织结构，其中有异型细胞，并常见淋巴上皮病表现及容易侵犯血管壁等特点，后组形态与淋巴结内淋巴瘤无异；据临床分析，前组以局部破坏及发烧为主，后者以鼻塞、耳聋及局部肿块为主，因此我们认为：MMH可看作一种特殊类型的淋巴瘤，有其独立的临床病理特点。     

Malignant histiocytosis and related tumors. A clinicopathologic study of 42 cases using cytological, histochemical and ultrastructural parameters

Light and electron microscopical, immunohistochemical and clinical characteristics in 42 cases of malignant neoplasms, arising from true histiocytes, are described. These were separated in a lymphoma-like subtype, called true histiocytic lymphoma (29 patients) and a disseminated variant, called malignant histiocytosis (9 patients). In addition 4 related histiocytic tumors are discussed, including 2 tumors arising from interdigitating cells. Sinus pattern and cytologic features, especially 'window' nuclei, are emphasized as diagnostic criteria. Erythrophagocytosis was not a constant finding. Electron microscopic features, presence of acid phosphatase, acid alpha-naphthylacetate esterase, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, Ia-antigen and absence of B- and T-cell markers, were important in establishing the histiocytic nature or excluding a non-histiocytic tumor. A distinct male predominance existed (male:female = 2.5:1) with a higher relapse free period in females (p = 0.032). A high number of mitotic figures appeared to be a favourable sign, p = 0.020 and 0.019, for remission rate and relapse free period respectively. The degree of cell differentiation and the immunohistochemical pattern did not show a correlation with remission and relapse free period. Extranodal involvement and the presence of short profiles of endoplasmic reticulum were prognostically unfavourable signs. True histiocytic lymphomas showed a higher remission rate (p = 0.041) and relapse-free period (p = 0.017) than malignant histiocytosis.     

Hepatosinusoidal leukaemia/lymphoma consisting of epstein-barr virus-containing natural killer cell leukaemia/lymphoma and T-cell lymphoma; mimicking malignant histiocytosis

Previously diagnosed cases of hepatosinusoidal T-cell lymphoma and malignant histiocytosis (MH) may include lymphoid neoplasms of natural killer (NK) cell lineage associated with Epstein-Barr virus (EBV). Such hepatosinusoidal neoplasms were found to demonstrate hepatomegaly but not lymphadenopathy, and all were diagnosed by a liver biopsy. Sixteen adult patients diagnosed with hepatosinusoidal leukaemia/lymphoma (six NK-cell leukaemia/lymphomas [NKLLs], five instances of MH, three T-cell malignant lymphomas [T-MLs], and two adult T-cell leukaemia/lymphomas [ATLLs] were examined for EBV by in situ hybridization, then were studied immunohistochemically and subjected to a DNA analysis. Among our five patients with MH, neoplastic cells showed T-cells, but no histiocytic markers, and they were considered to have either a T-cell or NK-cell lineage. All NKLLs, MHs and T-MLs, except for ATLLs accompanied by reactive hemophagocytic histiocytes, varied in number in each case. In situ hybridization revealed the presence of EBV in the nuclei of atypical cells in all of the six lymphoid neoplasms of NK-cell lineage. Each case of MH and each T-ML which represented EBV demonstrated no definite T-cell or histiocytic markers. Patients with ATLL did not reveal EBV. In all patients with hemophagocytosis, EBV was present in the nuclei of the neoplastic lymphocytes, but not in the hemophagocytic cells. Finally, the 16 cases were reclassified into eight cases with EBV -containing NKLLs, six T-MLs, and two ATLLs. In addition, no true histiocytic neoplasms were observed. The mechanism of hemophagocytosis may be therefore the production of lymphokines (macrophage-activating factors) by neoplastic lymphocytes. EBV-associated hepatosinusoidal leukaemia/lymphoma may thus contain a lymphoid neoplasm of NK-cell lineage, which made it difficult to be distinguished from the previously designated malignant histiocytosis.     

Modified total body irradiation as a planned second high-dose therapy with stem cell infusion for patients with bone-based malignancies

PURPOSE: To estimate the maximum tolerated dose of hyperfractionated total marrow irradiation (TMI) as a second consolidation after high-dose chemotherapy with autologous or syngeneic blood stem cell transfusion for patients with bone/bone marrow-based malignant disease. PATIENTS AND METHODS: Fifty-seven patients aged 3-65 years (median, 45 years), including 21 with multiple myeloma, 24 with breast cancer, 10 with sarcoma, and 2 with lymphoma, were treated with 1.5 Gy administered twice daily to a total dose of 12 Gy (n = 27), 13.5 Gy (n = 12), and 15 Gy (n = 18). Median time between the 2 transplants was 105 days (range, 63-162 days). RESULTS: All patients engrafted neutrophils (median, Day 11; range, Day 9-23) and became platelet independent (median, Day 9; range, Day 7-36). There were 5 cases of Grade 3-4 regimen-related pulmonary toxicity, 1 at 12 Gy, and 4 at 15 Gy. Complete responses, partial responses, and stabilizations were achieved in 33%, 26%, and 41% of patients, respectively. Kaplan-Meier estimates of 5-year progression-free survival and overall survival for 56 evaluable patients are 24% and 36%, respectively. Median time of follow-up among survivors was 96 months (range, 77-136 months). CONCLUSION: Total marrow irradiation as a second myeloablative therapy is feasible. The estimated maximum tolerated dose for TMI in a tandem transplant setting was 13.5 Gy. Because 20% of patients are surviving at 8 years free of disease, further studies of TMI are warranted.     

非霍奇金淋巴瘤免疫分型与骨髓细胞形态学的相关性研究

目的:探讨非霍奇金淋巴瘤免疫分型与骨髓细胞形态学的相关性。方法:选择2015年3月至2017年3月我院收治的NHL骨髓侵犯患者63例,进行骨髓涂片细胞形态学检测与流式细胞（FCM）免疫分型检测,分析两种检测之间的联系。结果:按照骨髓细胞形态学分型结果,63例NHL骨髓侵犯患者其中小细胞成熟细胞型40例（63.49%）、大细胞原始型患者6例（9.52%）、大细胞幼稚型10例（15.87%）以及组织细胞型7例（11.11%）。FCM检测根据骨髓瘤细胞特异性抗原表达情况,诊断为B细胞淋巴瘤患者48例（76.19%）、T细胞淋巴瘤患者10例（15.87%）、NK细胞淋巴瘤患者4例（6.35%）以及间变性大细胞淋巴瘤患者1例（1.59%）。FCM诊断48例B细胞淋巴瘤患者中,小细胞成熟细胞型37例（77.08%）、大细胞原始型4例（8.33%）、大细胞幼稚型5例（10.42%）、组织细胞型2例（4.17%）;10例T细胞淋巴瘤患者中,小细胞成熟细胞型3例（30.00%）、大细胞原始型2例（20.00%）、大细胞幼稚型1例（10.00%）、组织细胞型4例（40.00%）;4例NK细胞淋巴瘤患者中,均为大细胞幼稚型（100.00%）;1例间变性大细胞淋巴瘤患者为组织细胞型（100.00%）。结论:非霍奇金淋巴瘤免疫分型与骨髓细胞形态学之间具有着一定的联系,二者联合运用,可提高临床诊断准确性并为临床提供相应的病理分型意见,值得临床推广。     

噬血细胞综合征临床特点及预后影响因素分析(附27例)

目的:探讨噬血细胞综合征(hemophagocytic syndrome,HPS)的临床、实验室检查结果及预后影响因素,以提高对噬血细胞综合征的认识,了解影响预后的相关因素.方法:分析2012年01月至2020年01月我院收治的27例HPS患者的病因、临床表现、实验室检查结果及转归.结果:27例患者中,淋巴瘤相关HPS...     

青少年卵巢恶性肿瘤临床特点及预后分析

目的：了解青少年卵巢恶性肿瘤临床特点及预后的关系。方法：收集本院１９８５年～１９９４年间治疗的２０岁以下青少年卵巢恶性肿瘤２８例，并作了５年的跟踪随访。结果：本组青少年卵巢恶性肿瘤中生殖细胞肿瘤２４例（８５．７１％），上皮性肿瘤３例（１０．７１％），性索间质肿瘤１例（３．５７％）。１０例采用保留生育功能手术，其中３例治疗后正常分娩，６例采用卵巢癌根治术，１０例采用肿瘤细胞减灭术，５年生存率分别为６     

Sequential chemotherapy, high-dose thiotepa, circulating progenitor cell rescue, and radiotherapy for childhood high-grade glioma

Childhood malignant gliomas are rare, but their clinical behavior is almost as aggressive as in adults, with resistance to therapy, rapid progression, and not uncommonly, dissemination. Our study protocol incorporated sequential chemotherapy and high-dose thiotepa in the preradiant phase, followed by focal radiotherapy and maintenance with vincristine and lomustine for a total duration of one year. The induction treatment consisted of two courses of cisplatin (30 mg/m2) plus etoposide (150 mg/m2) x 3 days and of vincristine (1.4 mg/m2) plus cyclophosphamide (1.5 g/m2) plus high-dose methotrexate (8 g/m2), followed by high-dose thiotepa (300 mg/m2 x 3 doses), with harvesting of peripheral blood progenitor cells after the first cisplatin/etoposide course. From August 1996 to March 2003, 21 children, 14 females and 7 males, with a median age of 10 years were enrolled, 18 presenting with residual disease after surgery. Histologies were glioblastoma multiforme in 10, anaplastic astrocytoma in nine, and anaplastic oligodendroglioma in two; sites of origin were supratentorial areas in 17, spine in two, and posterior fossa in two. Of the 21 patients, 12 have died (10 after relapse, with a median time to progression for the whole series of 14 months; one with intratumoral bleeding at 40 months after diagnosis; and one affected by Turcot syndrome for duodenal cancer relapse). Four of 12 relapsed children had tumor dissemination. At a median follow-up of 57 months, overall survival and progression-free survival at four years were 43% and 46%, respectively. Sequential and high-dose chemotherapy can be afforded in front-line therapy of childhood malignant glioma without excessive morbidity and rather encouraging results.     

国产奥沙利铂治疗晚期复发、耐药消化道癌的临床观察

目的：评价国产奥沙利铂(艾恒)联合氟脲嘧啶，甲酰四氢叶酸治疗晚期复发、耐药消化道癌的近期疗效和不良反应。方法：进行开放性的临床研究，艾恒(L-OHP)130mg／m^2静脉滴注2小时，第1天；甲酰四氧叶酸(FA)200mg／m^2静脉滴注2小时，第1天～第5天；5-Fu500mg／m^2(不超过500mg／m^2，FA后)静脉滴注4小时，第1天～第5天。每3周重复一次。治疗3周期后按WHO标准进行疗效评价。结果：共治疗50例，其中47例可评价疗效，PR18例，NC18例，PD10例。总有效率38．3％。不良反应主要为外周神经毒性，胃肠道反应。结论：奥沙利铂治疗复发、耐药消化道癌的有效率高，不良反应轻，多数息者耐受良好，是治疗复发、耐药消化道癌的首选药物。