Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children’s Cancer Study Group.
Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children’s Cancer Study Group.
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儿童急性淋巴细胞白血病伴噬血细胞性淋巴组织细胞增多症的临床特征和遗传分析：九州山口儿童癌症研究组的日本回顾性研究。
DOI：
10.1007/s12185-014-1591-1
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发表时间：
2015
期刊：
影响因子：
2.1
通讯作者：
Kawano Y
中科院分区：
文献类型：
--
作者：
Moritake H;Kamimura S;Nunoi H;Nakayama H;Suminoe A;Inada H;Inagaki J;Yanai F;Okamoto Y;Shinkoda Y;Shimomura M;Itonaga N;Hotta N;Hidaka Y;Ohara O;Yanagimachi M;Nakajima N;Okamura J;Kawano Y
本研究旨在分析九州-山口儿童癌症研究组1996至2007年间登记的急性淋巴细胞性白血病(ALL)合并噬血细胞淋巴组织细胞增多症(HLH)患者。357例患者中有4例确诊，包括318例B细胞前体急性淋巴细胞白血病(BCP-ALL)中的2例和39例T细胞急性淋巴细胞白血病(T-ALL)中的2例。T-ALL患者的HLH率明显高于BCP-ALL患者(P=0.061)。HLH+ALL组确诊白血病的平均年龄为13.0岁，显著高于其余所有组观察到的6.05岁(P=0.001)。注意到女性倾向，因为所有四名患者都是女性(P=0.043)。在4例患者中，有2例的白血病细胞在6号染色体长臂出现缺失(P=0.003)。3例患者在维持治疗过程中出现促黄体生成素。细小病毒B19感染和巨细胞病毒重新激活分别被确定为1例和2例患者的HLH的原因。所有四名患者目前都处于完全缓解状态，尽管有一名患者在接受维持治疗后出现白血病复发。基于遗传分析，在所有患者中都发现了非同义的单核苷酸多态(SNPs)，这些SNPs分别位于UNC13D、Synaxin 11和STXBP。因此，临床医生应该意识到维持治疗期间发生HLH的风险，特别是在有家族性HLH致病基因SNPs的老年T-ALL患者中。
This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu–Yamaguchi Children’s Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (P= 0.061). The mean age of 13.0 years at the diagnosis of leukemia in the HLH + ALL group was significantly higher than the 6.05 years observed in the remaining ALL groups (P= 0.001). A female predisposition was noted, as all four patients were female (P= 0.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (P= 0.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) inUNC13D,syntaxin 11, andSTXBP2were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.