Acute lymphoblastic leukemia with t(1;19)(q23;p13)/TCF3-PBX1 fusion in an adult male with Down Syndrome.
Acute lymphoblastic leukemia with t(1;19)(q23;p13)/TCF3-PBX1 fusion in an adult male with Down Syndrome.
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患有唐氏综合症的成年男性患有 t(1;19)(q23;p13)/TCF3-PBX1 融合的急性淋巴细胞白血病。
DOI：
10.1159/000340049
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Tsuji K.
中科院分区：
文献类型：
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作者：
Yamamoto S;Ebihara Y;Mochizuki S;Tsuda M;Yuji K;Uchimaru K;Tojo A;Tsuji K.
染色体t(1；19)(q23；p13)异常导致TCF3-Pbx1融合转录本的产生，是儿童B前体急性淋巴细胞白血病(ALL)的常见易位之一[1]，但在成人中较为罕见[2]。虽然唐氏综合症(DS)患者在出生后的前三十年有较高的ALL风险[3]，但很少有报告描述患有DS和ALL的成年人[4，5]。本文报告1例成人DS患者，诊断为t(1；19)(q23；p13)/TCF3-Pbx1融合，合并凝血障碍和脑梗塞。28岁男性DS患者因高热入院。他没有血液紊乱或心血管异常的病史。体格检查显示颈部淋巴结肿大，直径2厘米。无肝脾肿大。血象：血红蛋白14.2g/dl，白细胞16.9×109/L占59%，血小板66×109/L，乳酸脱氢酶3.446IU/L，骨髓检查CD10、CD19、胞浆CD79a、HLADR、TdT阳性，CD3、CD13、CD20、CD33、CD34阴性。骨髓细胞染色体分析显示47，XY，+21[6]/49，idm，t(1；19)(q23；p13)。3)、-5、-7、-13[6]。逆转录-聚合酶链式反应证实了TCF3-Pbx1重排的存在。该患者随后被诊断为B-前体ALL伴t(1；19)(q23；p13)/TCF3-Pbx1。未检测到Janus激酶2突变。无中枢神经系统(CNS)受累。采用长春新碱、强的松龙、环磷酰胺、L-天门冬酰胺酶、吡柔比星联合诱导化疗方案。最初的PSL反应很差。诱导治疗第14天凝血试验结果如下：血小板计数34×109/L；凝血酶原时间比值1.18(正常：0.9~1.1)；纤维蛋白原56 mg/dl(正常：175~430 mg/dl)；纤维蛋白降解产物71 mg/L(正常：4.0 mg/L)；D-二聚体50.5 mg/L(正常：0.5 mg/L)；抗凝血酶III活性水平87%(正常：80~120%)。根据国际血栓与止血学会的诊断标准诊断为弥散性血管内凝血(DIC)，开始静脉注射重组血栓调节蛋白(RTM)。L-天冬氨酸第15天给药推迟。他在接受RTM治疗6天后从DIC中恢复，但在第20天出现意识模糊和左侧偏瘫。第21天磁共振成像(MRI)显示右侧颞叶亚急性脑梗塞。由于第21天AT III活性较低(37%)，我们判断高凝状态可能导致血栓栓塞症。然后，开始抗凝治疗，10天后，除轻度左侧偏瘫外，他的神经症状都有所改善。在那之后，他接受了MEC(米托蒽醌、依托泊苷和阿糖胞苷)[7]和Hyper CVAD(环磷酰胺、长春新碱、阿霉素和地塞米松)[8]治疗，但没有达到完全缓解(CR)。最初诊断7个月后观察到中枢神经系统受累，2个月后死于原发病。
The chromosomal abnormality t (1; 19)(q23; p13), leading to the production of the TCF3-PBX1 fusion transcript, is one of the common translocations in pediatric B precursor acute lymphoblastic leukemia (ALL)[1], but it is rarer in adults [2]. Although Down syndrome (DS) patients have a high risk of developing ALL in the first three decades of life [3], few reports have described adults with DS and ALL [4, 5]. We here report the first case of an adult patient with DS who was diagnosed as having ALL with t (1; 19)(q23; p13)/TCF3-PBX1 fusion, complicated by coagulopathy and cerebral infarction.A 28-year-old male with DS was admitted to our hospital because of high fever. He had no history of blood disorders or cardiovascular anomaly. Physical examination showed cervical lymphadenopathy of 2 cm in diameter. Hepatosplenomegaly was absent. Hemogram findings were as following: hemoglobin, 14.2 g/dl; white blood cell count, 16.9× 10 9/l with 59% blasts, and platelet count, 66× 10 9/l. The LDH value was 3,446 IU/l. The bone marrow examination revealed marked hypercellularity with 85% blasts, which were positive for CD10, CD19, cytoplasmic CD79a, HLA-DR, and TDT but negative for CD3, CD13, CD20, CD33, and CD34. Chromosomal analysis of bone marrow cells revealed 47, XY,+ 21 [6]/49, idem, t (1; 19)(q23; p13. 3),–5,–7,–13 [6]. Reverse transcription-polymerase chain reaction analysis confirmed the presence of the TCF3-PBX1 rearrangement. This patient was then diagnosed as having B-precursor ALL with t (1; 19)(q23; p13)/TCF3-PBX1. Janus kinase 2 mutation was not detected. Central nervous system (CNS) involvement was absent. An induction chemotherapy regimen based on vincristine, prednisolone (PSL), cyclophosphamide, L-asparaginase (L-ASP), and pirarubicin was administered. The initial PSL response was poor. On day 14 of induction therapy, the coagulation test showed the following results: platelet count, 34× 10 9/l; prothrombin time ratio, 1.18 (normal: 0.9–1.1); fibrinogen, 56 mg/dl (normal: 175–430 mg/dl); fibrin degradation products, 71 mg/l (normal:< 4.0 mg/l); D-dimer, 50.5 mg/l FEU (normal:< 0.5 mg/l FEU), and antithrombin III (AT III) activity level, 87%(normal: 80–120%). A diagnosis of disseminated intravascular coagulation (DIC) was made according to the diagnostic criteria of the International Society of Thrombosis and Hemostasis, and intravenous administration of recombinant thrombomodulin (rTM) was started. The administration of L-ASP on day 15 was postponed. He recovered from the DIC after 6 days of the administration of rTM, but had clouding of consciousness and left-sided hemiparesis on day 20. Magnetic resonance imaging (MRI) on day 21 showed a subacute cerebral infarction of the right temporal lobe. Since AT III activity was low (37%) on day 21, we judged that the hypercoagulation status might induce thromboembolism. Then, anticoagulation therapy was begun, and his neurological symptoms, except mild left hemiparesis, were improved 10 days later. After that, he received MEC (mitoxantrone, etoposide, and cytarabine)[7] and hyper CVAD (cyclophosphamide, vincristine, Adriamycin, and dexamethasone)[8] treatment but did not achieve complete remission (CR). CNS involvement was observed 7 months after the initial diagnosis, and he died of the primary disease 2 months later.