Glucocorticoid induced adrenal suppression in childhood acute lymphoblastic leukemia

Tijdschrift voor Kindergeneeskunde -     

Optimized treatment of childhood B-lineage acute lymphoblastic leukemia北大核心CSCD

儿童急性淋巴细胞白血病约占整体儿童白血病的75%,其中,急性B淋巴细胞白血病占儿童急性淋巴细胞白血病的80%以上。半个世纪以来,利用新技术不断发现新的分子生物靶标并用于精准的疾病预后分层,儿童急性淋巴细胞白血病的5年总生存率逐年提高。随着对远期生活质量的关注日益增强,儿童急性B淋巴细胞白血病的治疗从诱导治疗到维持治疗强度在不断优化,包括髓外白血病治疗去除放疗也有尝试,并获得成功。优化治疗的实现也得益于免疫学、分子生物学相关新技术的发展、规范化临床队列及与之相应的生物样本库建立。该文对近年来精准分层的实施及急性B淋巴细胞白血病降低强度优化治疗的相关研究进行梳理总结,为临床医生提供参考。     

Pharmacogenetics influence treatment efficacy in childhood acute lymphoblastic leukemia

Pharmacogenetics covers the genetic variation affecting pharmacokinetics and pharmacodynamics, and their influence on drug-response phenotypes. The genetic variation includes an estimated 15 million single nucleotide polymorphisms (SNPs) and is a key determinator for the interindividual differences in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far focus has mainly been on the widely used glucocorticosteroids, methotrexate, and thiopurines, or on metabolic pathways and transport mechanisms that are common to several drugs, such as the glutathione S-transferases. However, beyond the thiopurine methyltransferase polymorphisms, the candidate-gene approach has not established clear associations between polymorphisms and treatment response. In the future, high-throughput, low-cost, genetic platforms will allow screening of hundreds or thousands of targeted SNPs to give a combined gene-dosage effect (=individual SNP risk profile), which may allow pharmacogenetic-based individualization of treatment.     

Fatal adenovirus hepatitis during maintenance therapy for childhood acute lymphoblastic leukemia

Disseminated adenoviral infection with hepatitis is rare in children undergoing standard chemotherapy. We report on a 3(1/2)-year-old male with fatal adenovirus hepatitis receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL). Adenoviral hepatitis was proven by histology, viral culture, and PCR in a liver biopsy. Quantitative real-time PCR in the peripheral blood showed adenoviral DNA copy number >10(9)/ml. Despite aggressive supportive care and antiviral treatment with cidofovir, the patient died rapidly due to fulminant liver failure. Diagnostic and treatment options for adenovirus infection remain unsatisfactory for these patients. We propose suggestions for diagnosis and therapy.     

Fatal adenovirus hepatitis during standard chemotherapy for childhood acute lymphoblastic leukemia

Fulminant hepatitis is a rare complication of adenoviral infection that has not previously been reported in children receiving standard chemotherapy for acute leukemia. The authors have observed fatal adenovirus hepatitis in three children receiving first-line chemotherapy for acute lymphoblastic leukemia (ALL). The patients presented 10, 17, and 8 months into therapy according to the UKALL XI (third intensification), UKALL 97/99 (maintenance), and pilot UKALL 2003 (delayed intensification II) protocols, respectively. All patients received aggressive supportive care and intravenous immunoglobulins. The second and third patients were also treated with intravenous cidofovir. Despite these measures, all three children deteriorated rapidly and died of fulminant liver failure. Although rare, adenovirus infection should be considered in the differential diagnosis of acute hepatitis in children receiving standard chemotherapy for ALL.     

Results of treatment of high risk childhood acute lymphoblastic leukemia

Sixteen children with high risk acute lymphoblastic leukemia (ALL) who had one or more of the following risk factors: white cell count over 50 × 10⁹/liter, mediastinal mass, age under 2 or over 10 years, extramedullary involvement, or T-cell markers, were treated by a new protocol. All attained complete remission and 11 are still in their continuous first remission for 6-53 months. High activity of adenosine deaminase (ADA) in the leukemic cells seems to be an independent risk factor, as in the high ADA level group, 4 out of 7 patients relapsed and died, while none of the 8 patients with low ADA levels relapsed or died.     

儿童急性淋巴细胞性白血病治疗策略的思考

急性淋巴细胞性白血病(acute lymphoblastic leukemia,ALL)是儿童期最常见的恶性肿瘤.在过去30年中,随着诊断、分型水平的提高和治疗方案的改进,治愈率有了很大的提高.国际上的先进治疗组通过多中心研究,提出了很多先进的诊治理念与手段,并收到很大的成效.国内由于经济、社会或医疗条件所限,在实际工作中未能充分地利用上述成果;同时,单中心、分散、缺乏多中心协作的现状,使得很难找到具有充足说服力的研究结论.     

左旋门冬酰胺酶在儿童急性淋巴细胞白血病中的应用

小儿急性淋巴细胞白血病 (ＡＬＬ)的疗效近 10多年来有了很大的提高 ,其 5年无病生存 (ＥＦＳ)率已达 80 %甚至更高。这主要是因为应用了以左旋门冬酰胺酶 (Ｌ ａｓｐａｒａｇｉ ｎａｓｅ ,Ｌ ａｓｐ)和蒽环类的抗癌药如柔红霉素 (ＤＮＲ)及去甲氧柔红霉素 (ＩＤ)为主的联合诱导方案 ,以及加强了髓外白血病的预防措施的结果。尽管小儿ＡＬＬ有如此好的疗效 ,但仍有约 2 0 %的病例治疗失败 ,分析其原因 ,一是因为早期药物的毒副作用发生并发症死亡 ;另一是后期的复发。在这两者中 ,Ｌ ａｓｐ都占有非常重要的位置 ,故详尽地了解其在小儿ＡＬ…     

Ikaros基因与儿童急性淋巴细胞白血病预后的关系

Ikaros是淋巴细胞发育和增殖所必需的转录因子,在部分儿童急性淋巴细胞白血病(ALL)中表现为不同的缺失状态,其中以Ik6显性负相亚型过表达多见.Ikaros缺失是B祖细胞型ALL患者预后不良的一个独立危险因素.国外学者最近还确立了ALL的一种新亚型"BCR/ABL1-like ALL",同样以Ikaros缺失、预后不良为主要特征.由此推测,Ikaros对儿童ALL的诊断和治疗可能起着关键的作用.     

Ikaros基因与儿童急性淋巴细胞白血病预后的关系

Ikaros是淋巴细胞发育和增殖所必需的转录因子,在部分儿童急性淋巴细胞白血病(ALL)中表现为不同的缺失状态,其中以Ik6显性负相亚型过表达多见.Ikaros缺失是B祖细胞型ALL患者预后不良的一个独立危险因素.国外学者最近还确立了ALL的一种新亚型"BCR/ABL1-like ALL",同样以Ikaros缺失、预后不良为主要特征.由此推测,Ikaros对儿童ALL的诊断和治疗可能起着关键的作用.     

Fasting hypoglycemia is common during maintenance therapy for childhood acute lymphoblastic leukemia

Nineteen of 35 children (54%) with acute lymphoblastic leukemia receiving maintenance therapy consisting of daily oral 6-mercaptopurine and weekly oral methotrexate developed hypoglycemia (blood glucose level <2.7 mmol/L [50 mg/dL] or <2.9 mmol/L [54 mg/dL] with symptoms) during 16 hours of overnight fasting. In 15 of 15 re-studied children, fasting tolerance had improved, and in 67% (10/15), it had become normal a few months after cessation of therapy.