侵袭性NK细胞白血病1例并文献复习

目的：提高对侵袭性NK细胞白血病（ANKL）的认识。方法：报告1例ANKL患者并结合文献进行复习。结果：患者高热、肝脾肿大、进行性血细胞减少、外周血大颗粒淋巴细胞异常增多、骨髓中异常细胞增多并伴吞噬血细胞现象等,白血病细胞免疫表型为CD2、CD56阳性,CD3、CD4、CD8和CD57阴性,临床进展迅速。结论：ANKL为一种少见疾病,除临床表现外,诊断时需结合白血病细胞的免疫表型并需注意与其他相关疾病的鉴别,该病常呈侵袭性进展,治疗效果欠佳,预后极差。     

侵袭性NK细胞白血病一例并文献复习

目的 提高对侵袭性NK细胞白血病（ANKL）的认识.方法 报道1例ANKL患者并复习相关文献.结果 ANKL病情呈高度侵袭性,生存期短,以发热、淋巴结肿大、脾脏大、黄疸、肝功能异常为主要表现.外周血及骨髓中发现大颗粒淋巴细胞增多,免疫表型特征为CD2^＋、CD7^＋、CD56^＋、CD38^＋、HLA-DR^＋,TCR重排阴性.患者短期内出现多脏器衰竭,预后差.结论 ANKL是一种较罕见的白血病,易误诊,应及时进行免疫学表型、基因重排、病理组织学及细胞遗传学检查明确诊断,及时治疗.     

侵袭性自然杀伤细胞白血病14例临床分析

 目的　加深对侵袭性自然杀伤细胞白血病（ANKL）临床与实验室特点的认识。方法　回顾性分析14例ANKL患者的临床资料。结果　ANKL临床多表现为高热,热峰≥38.6 ℃,肝、脾大,淋巴结肿大;血细胞减少,肝功能及凝血功能异常;血清铁蛋白、乳酸脱氢酶水平升高。骨髓中可发现一群免疫表型为CD+2、CD+56、HLA-DR（+）、CD-3 的异常细胞;疾病在诊断时多已累及全身,短期内出现全身多系统、多脏器衰竭至死亡。结论　ANKL是一组临床进展迅速的恶性血液系统疾病,预后差,死亡率高。骨髓异常细胞免疫表型检测有助于诊断。     

侵袭性NK细胞白血病合并噬血细胞综合征一例并文献复习

目的 提高对侵袭性NK细胞白血病(ANKL)合并噬血细胞综合征(HPS)的认识.方法 回顾性分析1例ANKL合并HPS的临床资料,并复习相关文献.结果 患者为中年男性,以发热、咳嗽为首发症状,结合临床、骨髓象和细胞免疫表型等,确诊为ANKL合并HPS.最后死于多器官衰竭.结论 ANKL患者发病急,病情重,疾病进展快,当合并HPS时短期内可出现多器官衰竭,预后差,极易误诊和延误治疗.     

侵袭性自然杀伤细胞白血病三例并文献复习

目的：提高对侵袭性自然杀伤细胞白血病（ANKL）的认识。方法回顾性分析3例 ANKL患者的临床资料并复习相关文献。结果 ANKL 呈高度侵袭性，疾病异质性强，多以不明原因高热、肝脾淋巴结肿大、黄疸、肝损害、血细胞减少为主要临床表现，外周血及骨髓中可见大颗粒淋巴细胞浸润，免疫表型 CD2+、CD7+、CD56+，TCR 重排阴性，病程进展快，多数患者短期内死于多脏器衰竭。例1患者经培门冬酶、吉西他滨为主的化疗后行异基因造血干细胞移植（allo-HSCT）治疗获长期生存。结论 ANKL 是一种少见类型的白血病，预后差，以培门冬酶、吉西他滨为主的化疗方案以及 allo-HSCT 有望改善 ANKL的预后。     

侵袭性NK细胞白血病1例并文献复习

目的：加强对侵袭性NK细胞白血病(ANKL)的认识。方法：报告我们新近诊断的1例ANKL患者并进行文献复习。结果：ANKL高发于亚洲人群,其发病与EB病毒感染高度相关;白血病细胞的免疫表型特征为CD2^ 。sCD3^-,CD3^ ,CD56^ ,TCR重排阴性：临床病程进展快速,预后差;主要应与结外NK／T淋巴瘸和惰性NK细胞淋巴细胞增生性疾患相鉴别。结论：ANKL是一种少见的白血病。遇有疑似病例应及时做免疫学表型、基因重排和病理组织学检测,以明确诊断。     

侵袭性NK细胞白血病九例

 目的　提高对侵袭性NK细胞白血病（ANKL）的认识。方法　回顾分析2004年3月至2007年3月期间收治的9例ANKL患者的临床资料。结果　ANKL患者多有全身症状、肝脾大、淋巴结肿大、肝功能异常、贫血、中性粒细胞减少、血小板减少。大部分骨髓侵犯为轻、中度。肿瘤细胞免疫表型sCD-3、CD+56,可同时表达CD2、CD7、CD8、CD11b。3例患者有细胞遗传学异常,但未发现重现性染色体异常,TCR基因重排均为胚系构型。ANKL病程进展迅速,易发生多器官衰竭,中位生存时间9周。获得和未获得完全缓解（CR）患者生存时间分别为50周和3周。结论　ANKL为来源于成熟NK细胞的恶性肿瘤,具有独特的临床特征和免疫表型。病程呈侵袭性,对化疗不敏感,大部分患者短期内死亡。获得CR患者生存期明显延长,但难免复发,治愈率没有提高。     

以会阴部包块为主要表现的自然杀伤细胞白血病一例

 目的　提高对侵袭性自然杀伤（NK）细胞白血病（ANKL）的认识。方法　报道以会阴部包块为主要表现的NK细胞白血病1例。结果　ANKL高发于亚洲人群,其发病与EB病毒感染有关;临床病程进展迅速,侵袭性强,预后差;白血病细胞形态特征似原、幼淋巴细胞,过氧化物酶染色阴性,免疫表型有CD56的高表达,髓系及T、B淋巴细胞分化抗原表达均为阴性。结论　ANKL为少见白血病,临床表现和细胞形态可疑者应及时行免疫表型、基因重排和病理组织学检测,以明确诊断。     

侵袭性NK细胞白血病一例并文献复习

 【摘要】　目的　提高对侵袭性NK细胞白血病（ANKL）的认识。方法　报道1例ANKL患者临床诊疗经过，复习国内外文献，介绍ANKL目前相关研究进展。结果　该例为中年女性患者，以头痛、皮下出血为首发症状，伴反复低热、脾大，骨髓中异常细胞增多。细胞免疫表型CD+56、 CD+2、CD+7、CD+38、HLA-DR（+）、TCRα／β（-）、CD-3、CD-4、CD-5、CD-8。确诊为ANKL，予VMLP及VTLP等方案多疗程化疗，并行阿糖胞苷鞘内注射，达到部分缓解。结论　ANKL临床罕见，病程多呈爆发性发展，临床表现多样，初期极易误诊，缺乏大宗循证医学证据，化疗疗效差，中位生存期2个月左右。细胞免疫表型、骨髓病理甚至染色体核型分析可协助诊断。以左旋门冬酰胺酶为基础的化疗可能对ANKL的诱导缓解有较好疗效。     

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。     

流式细胞术在侵袭性NK细胞白血病诊断中的价值:一例报道并文献复习

 目的　分析侵袭性NK细胞白血病的临床特征及诊治方法,探讨流式细胞术（FCM）对其诊断的价值。方法　分析1例侵袭性NK细胞白血病患者的临床特征,并进行文献复习。结果　患者持续高热、肝脾进行性增大、血三系细胞减少,骨髓中可见不典型细胞,FCM检查示骨髓中NK细胞约占淋巴细胞的83.3 %,免疫表型为CD34-、CD2+、CD7+、CD3-、CyCD3+、CD5-、CD16+、CD56+、CD30-、CD4-、CD8-、CD117-、CD11c-、CD19-、CD45++、SSC+～++,TCR、IgH基因重排阴性,染色体正常,诊断为侵袭性NK细胞白血病。结论　侵袭性NK细胞白血病是一种少见的血液系统恶性疾病,临床表现多样、疾病进展迅速,早期容易误诊,FCM免疫分型结合骨髓细胞学涂片具有简便、快捷、可行、创伤性小的优势,在一些特殊情况下可作为首选检测手段。     

Aggressive natural killer-cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells.

Aggressive natural killer-cell leukemia (ANKL) is a rare form of large granular lymphocyte leukemia, which is characterized by a systemic proliferation of NK cells. The clinical features of 22 ANKL cases were analyzed. Hepatomegaly (64%), splenomegaly (55%) and lymphadenopathy (41%) were also frequently observed. Leukemic cells were identified as CD1-, CD2+, surface CD3-, CD4-, CD5-, CD7+, CD8+/-, CD10-, CD11b+/-, CD13-, CD16+, CD19-, CD20-, CD25-, CD33(-), CD34-, CD38+, CD56+, CD122+, HLA-DR+ and TCR-. Two of the 16 cases examined for CD57 were positive and three of the seven cases examined for cytoplasmic CD3. Epstein-Barr virus was detected in the tumor cells of 11 of the 13 cases examined. No common cytogenetic abnormalities were identified and 6q anomaly was detected in only one. Three of 13 patients treated with chemotherapy containing anthracycline/anthraquinone attained complete remission, in contrast to none of the eight who were treated with regimens without anthracycline. Although the overall prognosis was poor with a median survival of 58 days, those who attained remission showed better prognosis (P=0.005). These findings suggest that ANKL is an entity of mature cytotoxic NK-cell neoplasms with distinct phenotype and disease presentations. Intensive treatment for ANKL may result in a better prognosis.     

侵袭性NK细胞白血病并发多器官衰竭一例并文献复习

 目的　提高对侵袭性NK细胞白血病（ANKL）及并发多器官功能衰竭（MOF）的认识。方法　报道1例罕见ANKL的诊断、治疗经过并结合文献复习讨论。结果　患者经骨髓、免疫表型等检查确诊ANKL,发病及治疗过程中并发MOF（肝、肾、心、肺等）、代谢性酸中毒、肿瘤溶解综合征、弥漫性血管内凝血（DIC）。予VP方案化疗和相应对症治疗曾一度好转,但很快死于呼吸、循环功能衰竭。结论　ANKL易发生髓外浸润,并发MOF,病情凶险,预后差。     

Stromal populations and fibrosis in human long-term bone marrow cultures.

An immunofluorescence study of the adherent layer of human long-term bone marrow cultures (HLTBMC) revealed the following surface markers on the different stromal cell populations: stromal fibroblastic cells CD10+, FIB86.3+, CD13+, CD71+; adipocytes CD10+, FIB86.3-, CD13+, CD71-/+; and macrophages CD10-/+, FIB86.3+, CD13+, CD71-/+, CD14+, CD33+, CD25+, HLA-DR+, CD4+, CD19+, CD45+. The markers of the stromal fibroblastic cells in HLTBMC were similar to those of twice-passaged fibroblasts not only from bone marrow and spleen, but also from a hemopoietic non-supportive organ such as the skin. Some of the cultured human umbilical vein endothelial cells used as controls were found to be CD25+, demonstrating for the first time the interleukin-2 receptor p55 chain on normal non-hemopoietic cells. The stromal fibroblastic cells are overrepresented compared to the small non-macrophage hemopoietic cell population in the adherent layer of HLTBMC. In addition, silver staining revealed an increased reticulin content in most of the HLTBMC. An excessive growth of stromal fibroblastic cells and an excessive deposition of their product, the reticulin fibers, are the hallmark of myelofibrosis. The finding of equivalent observations in HLTBMC suggests that the hitherto unexplained, premature quenching of hemopoiesis in HLTBMC might at least partly be due to mechanisms similar to those operating in myelofibrosis in vivo.     

Multipotent and committed CD34+ cells in bone marrow transplantation.

In order to study the role of CD34+ cells in hematological recovery following bone marrow transplantation (BMT), bone marrow cells stained with HPCA-1 (CD34) and MY-9 (CD33) monoclonal antibodies were analyzed by using a fluorescence-activated cell sorter on or about days 14 and 28, as well as at later times, following BMT in 6 recipients. Single cell cultures of CD34+ cells were also performed to evaluate their in vitro hematopoietic function. CD34+ cells were detectable in bone marrow cells on day 14. More than 80% of CD34+ cells co-expressed the CD33 antigen, and macrophage (Mac) colony-forming cells predominated among total colony-forming cells of CD34+ cells. In normal bone marrow cells, CD34+, CD33+ cells amounted to about 40% of CD34+ cells, and the incidences of erythroid bursts, granulocyte/macrophage (GM) colonies, and Mac colonies were similar to each other. After more than 10 weeks, CD34+, CD33- cells gradually recovered, as erythroid burst colony-forming cells increased following GM colony-forming cells. This phenomenon was well-correlated with the time course of peripheral blood cell recovery. CD34+, CD33+ cells as committed progenitors and CD34+, CD33- cells as multipotent stem cells have distinctive biological behaviors in BMT.     

Complex karyotype including chromosomal translocation (8;14) (q24;q32) in one case with B-cell prolymphocytic leukemia

We report a case of a 64-year-old white female patient, who presented with symptomatic anemia (Hgb: 6.8g/dl), thrombocytopenia (platelets: 94,000/mcl) and leukocytosis (WBC: 156,000/mcl). Peripheral blood smear revealed markedly increased white blood cell count with predominance of atypical lymphoid cells of intermediate size, moderately dense chromatin, and prominent large single nucleoli. Bone marrow aspirate smear showed predominance (78%) of atypical lymphoid cells morphologically identical to those seen in the peripheral blood. The bone marrow core biopsy was hypercellular and packed with prominent infiltrate of prolymphocytes. Immunophenotypic analysis revealed a population of monoclonal cells (75% of all -erythroid cells) characterized by CD45+, CD19+, CD20+, CD5+, HLA-DR+, CD10-, CD23+/-, CD38+ and FMC7-. The abnormal cells were restricted to kappa light chain immunoglobulin with low intensity. Cytogenetic study showed an abnormal clone of eight cells with the following karyotype: 45,X,-X,add(8)(p11.2),t(8;14)(q24;q32),add(20)ql3[8]/46,XX[12]. The relative rarity of B-PLL and the heterogeneity of clinical and laboratory parameters make it difficult to define the natural history and prognosis in all cases. The optimal treatment for B-PLL is still unknown and to date there are no reports of chromosomal abnormalities as a prognostic factor. The patient was treated with six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Complete remission was achieved according to the criteria defined by National Cancer Institute Working Group for CLL.     

Sezary cell-like leukemia: a distinct type of mature T cell malignancy

We describe the clinical, ultrastructural, and immunophenotypical characteristics of four cases of an unusual type of T cell leukemia. Clinical features included high WBC, ranging from 26-148 x 10(9)/liter, bone marrow infiltration, splenomegaly, and lymphadenopathy. Skin involvement was not documented at presentation, but it was seen as a terminal event in one patient with a pattern of dermal lymphocytic infiltration different from that usually seen in Sezary syndrome. By ultrastructural analysis, the circulating lymphoid cells were indistinguishable from small Sezary cells in two cases, resembled large Sezary cells in one case, and consisted of a mixture of small Sezary cells and prolymphocytes in the remaining case. The cells from all cases had a mature T cell phenotype, TdT-, CD1a-, CD2+/-, CD3+, CD5+. In addition, the cells were either CD8+, CD4- or CD8+, CD4+ or CD4-, CD8-; and, in only one case, the findings were similar to those of Sezary syndrome cells: CD4+, CD8-, CD7-, BE-2+. In the latter case, serological and immunological assays were positive for HTLV-I while these were negative in two other patients investigated. The features of these patients suggest that Sezary cell leukemia is a distinct clinico-pathological entity although the alternative diagnosis of adult T cell leukemia/lymphoma could not be excluded in the HTLV-I+ case. Sezary cell leukemia appears to be resistant to current chemotherapy regimens and is associated with an aggressive clinical course and short survival.