小儿急性白血病细胞染色体分析及其与临床预后关系的探讨

为探讨白血病患儿细胞遗传学改变和临床预后的关系，我们对41例急性白血病初诊患儿进行细胞遗传学研究，28例异常核型检出（68％），其中急性淋巴细胞白血病异常核型检出率为67％，急性非淋巴细胞白血病异常核型检出率为73％。急性白血病患儿染色体结构异常可视为预后不佳的标志，而正常二倍体核型及超二倍体核型的白血病（尤其是超过50条的急淋）则预后较好，还对其中11例患儿核型进行动态观察，提示细胞遗传学研究可作为白血病患儿诊断分型、指导治疗和判断预后的重要指标。     

小儿急性白血病细胞染色体分析及其与临床预后关系的探讨

为探讨白血病患儿细胞遗传学改变和临床预后的关系，我们对４１例急性白血病初诊患儿进行细胞遗传学研究，２８例异常核型检出（６８％），其中急性淋巴细胞白血病异常核型检出率为６７％，急性非淋巴细胞白血病异常核型检出率为７３％。急性白血病患儿染色体结构异常可视为预后不佳的标志，而正常二倍体核型及超二倍体核型的白血病则预后较好，还对其中１１例患儿核型进行动态观察，提示细胞遗传学研究可作为白血病患儿诊断分型、指     

儿童难治复发急性淋巴细胞白血病的新治疗策略

儿童急性淋巴细胞白血病虽已取得显著疗效,但一旦出现复发或难治,其长期存活机会极少,预后不良。随着人们对儿童复发难治急性淋巴细胞白血病的分子生物学机制的深入认识,靶向治疗、免疫治疗等新的疗法被用于临床,且已取得较好的临床效果。文章就儿童难治复发急性淋巴细胞白血病的新疗法进行综述。     

急性白血病细胞遗传学研究及其临床意义

应用高分辨同步化染色体制备技术等对７０例小儿急性白血病进行细胞遗传学研究，５８例（初诊及复发）检出异常核型（８１％），其中急性淋巴细胞白血病异常核型检出率为７８％，急性非淋巴细胞白血病异常核型捡出率为８６％。对３１例患儿的核型与临床关系进行观察，发现小儿急性白血病染色体结构异常可视为预后不佳的标志，而正常二倍体核型及超二倍体核型的急性白血病（尤其是超过５０条的急性淋巴细胞白血病）则预后较好。还对８例小儿急性白血病核型进行动态观察以及对１２例持续完全缓解者进行随访，认为细胞遗传学研究对小儿急性白血病的诊断分型、预后判断及指导治疗具有重要意义。     

治疗相关白血病1例报告

目的探讨急性淋巴细胞白血病患者长期化疗后发生治疗相关骨髓增生异常综合征白血病(t-MDS/AML)的临床特征及预后。方法观察一例儿童急性淋巴细胞白血病经化疗后演变为幼年慢性粒-单核细胞白血病(JMML)的临床演变过程及治疗结果并进行相关文献复习。结果1例急性淋巴细胞白血病患儿经3年正规化疗停药后3月,外周血白细胞进行性增高并出现原始粒、单核细胞。各项检查支持幼年慢性粒-单核细胞白血病诊断。根据2000年WHO造血组织和淋巴组织肿瘤分类方法,归于MDS/MPD一类疾病。患者迅速进展为AML-M4b,治疗无效死亡。结论t-MDS比原发性MDS病情进展更快,预后更差。t-AML临床预后不良,骨髓移植及大剂量化疗仅对部分患者有效。应进一步加强儿童ALL患者的合理用药,根据不同危险度分型,选取相应治疗强度化疗方案,以减少t-MDS/AML发生的可能。     

急性淋巴细胞性白血病37例缓解期骨髓幼淋细胞升高的意义

目的 分析急性淋巴细胞性白血病缓解期骨髓幼淋细胞轻度升高(5%～10%)的原因及其临床意义.方法 回顾性分析上海儿童医学中心1998年-2005年急性淋巴细胞性白血病缓解期骨髓幼淋细胞轻度升高(5%～10%)的37例患儿,分析其幼淋细胞升高的原因及随访其治疗经过和预后.结果 急性淋巴细胞性白血病患儿缓解期骨髓幼淋细胞轻度升高患儿除1例复发以外,其余均缓解.大部分患儿骨髓幼淋细胞升高是化疗后再生的骨髓正常的B系淋巴细胞反应性增生,其中大部分骨髓幼淋细胞可自行恢复正常.另外,病毒感染亦可导致幼淋细胞升高.结论 急性淋巴细胞性白血病缓解期骨髓幼淋细胞轻度升高(5%～10%)是骨髓中正常的B系淋巴细胞反应性增生,预后良好.     

IKZF1基因在儿童急性B淋巴细胞白血病中的研究进展

IKAROS家族锌指转录因子1(ikaros family zinc finger 1,IKZF1)基因编码Ikaros蛋白,其调节造血细胞发育及分化,并对自身免疫和肿瘤抑制至关重要。随着基因组学的研究进展,IKZF1成为急性淋巴细胞白血病发生、发展的重要预后生物标志物。IKZF1基因突变在约15%的儿童急性B淋巴细胞白血病中存在。突变损害了IKZF1基因的肿瘤抑制功能,使白血病细胞增殖和抗凋亡能力增强,对关键化疗药物产生耐药。IKZF1突变在有其他预后不良因素的病例中更常见,在治疗过程中面临复发率高、缓解期短、病死率高的困难。对IKZF1基因突变的急性B淋巴细胞白血病儿童进行强化治疗、造血干细胞移植及免疫治疗可以降低复发率、提高缓解率及生存率。靶向治疗有希望改善IKZF1突变患儿的预后。     

儿童急性白血病染色体异常与预后关系研究进展

近年来,儿童急性白血病的预后有了很大的提高.急性淋巴细胞白血病(acute lymphoblastic leukemia, ALL)患儿5年无事件生存率(event-free survival, EFS)已经达到70%～80%,而急性髓系白血病(acute myeloid leukemia,AML)的5年EFS也达到50%左右,这得益于危险度分级和个体化治疗的广泛应用.白血病细胞的染色体/基因改变是影响预后的关键因素之一,以下就近年国内外对于儿童急性白血病染色体异常与预后关系的研究进展进行综述.     

儿童急性淋巴细胞白血病预后因素的研究进展

急性淋巴细胞白血病是儿童时期最常见的恶性肿瘤,随着治疗的进步,其预后已大大改善,但仍有20%左右患儿由于高度耐约而复发.因此,更要关注儿童急性淋巴细胞白血病预后的影响因素,实施基于危险因素分组的个体化治疗措施.目前影响其预后的因素有:白细胞计数、细胞或分子遗传学特征、免疫分型、早期治疗反应、微小残留病、药动学和药物遗传学及治疗反应.     

儿童急性白血病完全缓解后骨髓幼稚细胞低比例增高的临床意义

目的　了解急性白血病患儿完全缓解 (CR)后骨髓幼稚细胞比例出现 0 0 5～ 0 2 5时对预后的影响 ,为临床治疗策略的调整提供依据。方法　对 1998～ 2 0 0 1年上海儿童医学中心收治急性白血病患儿CR后按骨髓幼稚细胞比例分为A组 (<0 0 5 )和B组 (0 0 5～ 0 2 5 ) ;B组又分为B1(0 0 5～ 0 10 )、B2 (～ 0 15 )、B3(～ 0 2 5 ) 3个亚组 ,分析各组与急性白血病复发的关系。结果　急性淋巴细胞白血病 (ALL)患儿CR后骨髓幼稚细胞≥ 0 10时 ,复发率与阴性对照组差异有显著性 ;急性非淋巴细胞白血病 (ANLL)患儿CR后骨髓幼稚细胞≥ 0 15时 ,复发率与阴性对照组差异有显著性。结论　ALL患儿CR后骨髓中原始淋巴细胞 幼淋巴细胞≥ 0 10及ANLL患儿CR后骨髓中原始粒细胞 早幼粒细胞或原始单核细胞 幼单核细胞≥ 0 15时应考虑及时调整治疗方案。     

Detection of RAS gene mutation and its clinical significance in children with acute lymphoblastic leukemia北大核心CSCD

Objective To investigate the mutation rate of the RAS gene and its clinical significance in children with acute lymphoblastic leukemia. Methods A retrospective analysis was performed on the medical data of 120 children with newly diagnosed acute lymphoblastic leukemia, who were admitted to the Third Affiliated Hospital of Zhengzhou University from January 2015 to January 2020 and underwent next-generation sequencing. The clinical and molecular features were analyzed. The impact of RAS gene mutation on the overall survival rate was evaluated in these children. Results Among the 120 children, 35 (29.2%) had RAS gene mutation, 30 (25.0%) had KRAS gene mutation, and 5 (4.2%) had both NRAS and KRAS gene mutations. All NRAS mutations and 71% (25/35) of KRAS mutations were located at the 12th and 13th codons. RAS gene mutation was detected in 35 (33.3%) out of 105 children with B-lineage acute lymphoblastic leukemia, but it was not detected in those with acute T lymphocyte leukemia. Of all the children, 11 (9.2%) were lost to follow-up, and among the 109 children followed up, 16 (14.7%) died. The children with RAS gene mutation had a significantly lower 2-year overall survival rate than those without RAS gene mutation (P<0.05). The prognosis of children with RAS gene mutation combined with WT1 overexpression and WBC>50×109/L at diagnosis was worse (P<0.05). Conclusions RAS gene mutation is commonly observed in children with B-lineage acute lymphoblastic leukemia and may have an adverse effect on prognosis. © 2022 Xiangya Hospital of CSU. All rights reserved.     

Ӥ����Ѫ�����ν�չ

??Childhood acute lymphoblastic leukemia is the first disseminated cancer shown to be curable. Central nervous system leukemia ??CNSL?? is one of reasons that cause leukemia replase and is associated with a poor prognosis. Pediatricians should master the diagnostic techniques??modalities of prophylaxis and therapy of CNSL in patients with childhood acute lymphoblastic leukemia.     

儿童中枢神经系统急性淋巴细胞白血病诊治进展

儿童急性淋巴细胞白血病是可治愈性疾病,多数患儿经过系统化治疗可持续完全缓解,但仍有部分复发,其中中枢神经系统受累是导致患儿复发以及影响生存质量的重要原因之一。临床儿科医生对中枢神经系统急性淋巴细胞白血病的诊断、防治等相关进展应有所了解。     

��ͯ����T�ܰ�ϸ����Ѫ���ٴ���Ч��Ԥ���������73������

??Objective??To analyze the clinical characteristics and prognosis of pediatric acute T lymphoblastic leukemia. Methods??Clinical characteristics of 73 children with acute T lymphoblastic leukemia and T-cell lymphoblastic lymphoma involving the bone marrow treated in Peking University People’s Hospital from March 2003 to March 2014 were retrospectively analysed?? and the prognosis factors were analyzed. Results??Of the 73 patients?? 25 children relapsed and 3 died from complications during chemotherapy or transplantation. Their 5-year CRF was ??37.89±6.02??% and 5-year EFS was ??58.74±6.01??%. The 5-year EFS decreased significantly when the initial onset age was more than 13. The 5-year CRF increased significantly when the initial onset size of spleen was bigger than 9 cm under the costal margin or the IgH rearrangement was positive. The 5-year CRF decreased significantly and 5-year EFS increased significantly when average peak methotrexate ??MTX?? blood concentration was more than 40 μmol/L during high-dose MTX chemotherapy. Conclusion??The treatment result of children with T-ALL is unsatisfactory. Initial onset age ≥13 and huge spleen indicate poor prognosis. Positive IgH rearrangement may be associated with high risk of recurrence. T-ALL patients can benefit from high-dose MTX therapy.     

Secondary Hodgkin's disease in childhood acute lymphoblastic leukemia

Improved survival in childhood acute lymphoblastic leukemia has led to the occurrence of second malignancies in these patients. Hodgkin's disease is very rare as a second malignancy. We report three patients with acute lymphoblastic leukemia in remission who developed Hodgkin's disease. Although all had received low-dose irradiation, none received alkylating agents as part of their chemotherapy. Review of our cases and of 11 reported in the literature revealed unique aspects of this association. There was a short median interval of 19 months to the development of the second malignancy. Over one-third of the patients had uncommon sites of involvement (lung, tonsil, small bowel). The distribution of histologic subtypes was unusual, as 5 of 14 cases had lymphocyte depletion or unclassifiable Hodgkin's disease. The results of therapy were excellent. Our three patients are alive, with both malignancies in continuing remission. Two patients are off all therapy for 4 and 6 years, respectively. The third remains on antileukemic treatment. Secondary Hodgkin's disease in childhood acute lymphoblastic leukemia does not appear to have a poor prognosis and long-term survival and possible cure of both diseases may be achieved.     

儿童Ph-like急性淋巴细胞白血病的研究进展

费城染色体样急性淋巴细胞白血病(Ph-like ALL)是一组基因表达谱与费城染色体阳性ALL(Ph~+ALL)相似的B-ALL(B-lineage ALL)亚群,涉及一系列细胞因子受体基因及激酶信号通路异常活化的相关基因改变,并常伴淋系发育相关转录因子异常。Ph-like ALL在高危组儿童B-ALL的比例高达15%,其临床特征与不良预后相一致。酪氨酸激酶抑制剂(TKIs)联合化疗显著改善儿童Ph~+ALL预后提示基于Ph-like ALL分子遗传学异常的精准靶向治疗具有良好的研究前景。该文结合近年Ph-like ALL的相关研究进展,对儿童Ph-like ALL的基因改变及发病机制、临床特征、诊断及治疗进行综述。     

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。     

OCCURRENCE OF ACUTE NONLYMPHOBLASTIC LEUKEMIA IN TWO GIRLS AFTER TREATMENT OF RECURRENT, DISSEMINATED LANGERHANS CELL HISTIOCYTOSIS

The occurrence of Langerhans cell histiocytosis (LCH) and acute leukemia in one individual has rarely been observed. Despite few exceptions, two distinct patterns of association appear evident: acute lymphoblastic leukemia preceding LCH and LCH preceding acute nonlymphoblastic leukemia (ANLL). The latency of ANLL after the diagnosis of LCH is suggestive of a therapy-related process. This report describes two new cases in whom ANLL was diagnosed 7 years 8 months and 5 years 8 months after the start of initial treatment of disseminated recurrent LCH. Morphology showed blasts from FAB-type M4/M5 in the first patient, who died due to progression of leukemia. The second patient showed myelodysplastic syndrome (refractory anemia with excess of blasts in transformation; RAEB-t) and is now in remission from leukemia 3 years 11 months after allogeneic bone marrow transplantation. The review of a total of 26 patients with ANLL after LCH suggests that the disease has a poor prognosis and allogeneic BMT seems to be the treatment of choice.     

OCCURRENCE OF ACUTE NONLYMPHOBLASTIC LEUKEMIA IN TWO GIRLS AFTER TREATMENT OF RECURRENT,DISSEMINATED LANGERHANS CELL HISTIOCYTOSIS

The occurrence of Langerhans cell histiocytosis (LCH) and acute leukemia in one individual has rarely been observed. Despite few exceptions, two distinct patterns of association appear evident: acute lymphoblastic leukemia preceding LCH and LCH preceding acute nonlymphoblastic leukemia (ANLL). The latency of ANLL after the diagnosis of LCH is suggestive of a therapy-related process. This report describes two new cases in whom ANLL was diagnosed 7 years 8 months and 5 years 8 months after the start of initial treatment of disseminated recurrent LCH. Morphology showed blasts from FAB-type M4/M5 in the first patient, who died due to progression of leukemia. The second patient showed myelodysplastic syndrome (refractory anemia with excess of blasts in transformation; RAEB-t) and is now in remission from leukemia 3 years 11 months after allogeneic bone marrow transplantation. The review of a total of 26 patients with ANLL after LCH suggests that the disease has a poor prognosis and allogeneic BMT seems to be the treatment of choice.     

Intestinal obstruction at the onset of acute lymphoblastic leukemia in a child

Surgical complications need not be fatal in acute leukemia. If these are promptly diagnosed and properly treated, the prognosis will improve. This report deals with a case of acute lymphoblastic leukemia presenting with an acute abdomen following surgery for choledochal cyst. A peripheral blood smear and examination of the bone marrow revealed acute lymphoblastic leukemia. The child received transfusions of blood and platelets. Pretreatment with prednisolone was started as therapy for leukemia, and 2 days later, the patient underwent surgery. Therapy was continued until the general condition allowed a more aggressive form of treatment. Complete remission was achieved, and the patient is still in good health 48 months after diagnosis and 15 months after discontinuation of treatment. The favorable outcome in this child shows that prompt surgery is sometimes an essential step in the treatment of childhood leukemia.