儿童急性髓系白血病分子生物学相关研究进展

儿童急性髓系细胞白血病是一种造血干细胞恶性克隆性疾病,其中分子生物学异常在急性髓系白血病发生发展中起了关键作用.随着技术的进步,越来越多的分子异常被发现,这为患者的预后评估及靶向治疗提供依据.     

异基因造血干细胞移植治疗24例儿童髓系白血病疗效分析

与急性淋巴细胞性白血病相比,除M3之外的儿童急性髓系白血病(AML)缓解(CR)率较低,长期无病生存机会不足50%,复发、难治者预后更差,更多患儿需要借助造血干细胞移植才能获救.     

儿童急性髓系白血病治疗进展

急性髓系白血病(AML)是由于造血干细胞分化障碍及增殖过度所致异常骨髓造血前体细胞聚集的恶性克隆性疾病。近年来随着危险度分层的合理应用、靶向药物的不断研发、支持治疗的进步、造血干细胞移植技术的日渐成熟,儿童AML的生存率已经较前有明显提高。文章综述儿童AML的治疗进展。     

儿童难治性急性髓系白血病异基因造血干细胞移植现状

儿童急性髓系白血病(acute myeloid leukemia,AML)虽然发病率仅占儿童白血病的1/4,但是占儿童白血病死亡病例的1/2以上.与急性淋巴细胞白血病(ALL)相比,除M3之外的儿童AML完全缓解(complete remission, CR)率较低,仅半数患儿可获长期无病生存,复发、难治者预后更差,更多患儿需要借助造血干细胞移植(hematopoietic stem cell transplantation, HSCT)才能获救.     

携带β-地中海贫血基因的骨髓增生异常综合征转化为急性髓系白血病M_6 1例报告和文献复习

骨髓增生异常综合征(MDS)是一组起源于造血干细胞的获得性克隆性疾病,其特征性病理生理改变是克隆性造血干/祖细胞发育异常和无效造血,其基本临床特征是外周血细胞减少和红系、粒系、巨核细胞系一系或多系形态学异常,由于遗传不稳定因而高风险向急性髓系白血病(AML)转化[1].我院依照WHO于2003年制定的儿童MDS最低诊断标准诊断了1例MDS患儿,现报告如下.     

米托蒽醌、依托泊苷、阿糖胞苷方案治疗伴一系或多系病态造血的儿童急性髓系白血病的疗效

目的 探讨寻求伴一系或多系病态造血的儿童急性髓系白血病治疗方案,以期在短时间内达到完全缓解,为长期无病生存打下基础.方法 对DA或HA标准方案治疗1、2个疗程,无效的10例一系或多系病态造血的急性髓性白血病患儿采用自身对照的方法 .第2疗程化疗均采用米托蒽醌、依托泊苷、阿糖胞苷(MEA)方案,并辅以抗感染、成分输血、细胞因子应用等治疗.结果 10例患儿MEA方案治疗1个疗程,治疗中骨髓抑制期最长达19 d.中性粒细胞绝对值0～0.08×109 L-1,血小板(6～10)×109 L-1,白细胞升至3.5×109 L-1时 ,骨髓原始细胞8例下降至0.05以下,血小板恢复正常,Hb升高,8例获完全缓解,2例无效.结论 用MEA方案治疗伴一系或多系病态造血的急性髓系白血病儿童患者疗效较好.     

儿童急性髓系白血病治疗相关进展

急性髓系白血病（acutemyeloid leukemia，AML）是一组多异质性带有髓系特点的恶性疾病，白血病细胞丧失分化、成熟能力以及异常增殖，使恶性细胞在体内积累，造成正常造血功能低下。在儿童和青少年白血病中AML约占15～20％，绝大多数病人经治疗能获得完全缓解（complete remission，CR），31～54％的病人能被治愈。探讨AML预后因素并确定微量残余白血病（minimal residual disease，MRD）的检测意义以指导个体化化疗，应用新有效药物并改进化疗方案以增进疗效减少药物毒性，合理应用造血干细胞移植治疗高危AML儿童，促进了儿童AML疗效的改善。本文就以上内容的进展做一综述。     

二次移植治疗异基因造血干细胞移植后复发儿童急性白血病的临床疗效分析

目的 探讨二次单倍体移植治疗异基因造血干细胞移植后复发的儿童急性白血病的效果。方法 回顾性分析本中心2014年3月1日—2022年5月30日儿童急性白血病异基因造血干细胞移植术后复发后接受二次单倍体异基因造血干细胞移植的7例病例资料,其中急性髓细胞白血病5例,急性淋巴细胞白血病2例,分析二次移植后总体生存率、无病生存率、移植相关死亡率。结果 7例患儿均完成造血重建,粒细胞植入中位时间11(9-17)天,血小板植入中位时间13(9-18)天,随访至2022年5月30日,1例因原发病未缓解死亡,1例于移植+86天原发病复发,且合并休克、呼吸衰竭,家属放弃治疗死亡。2例合并慢性移植物抗宿主病(cGVHD),为皮肤局限型。1年总生存率(OS)71%(5/7),1年无病生存率(DFS)43%(3/7)。结论 二次单倍体异基因造血干细胞移植治疗儿童白血病疗效较好,是异基因造血干细胞移植后复发的儿童白血病患儿的治疗方法之一。     

儿童异基因造血干细胞移植后中枢神经系统淋巴增殖性疾病1例报告并文献复习

目的 探讨儿童异基因造血干细胞移植术(allo-HSCT)后中枢神经系统淋巴增殖性疾病(CNS-PTLD)的临床特点.方法 回顾分析1例行allo-HSCT患儿的临床资料,并复习相关文献.结果 患儿,13岁,男性,确诊为急性髓系白血病M 5型(TLS-ERG融合基因阳性),缓解化疗达完全缓解,TLS-ERG转为阴性,之...     

儿童急性髓系白血病的治疗

急性髓系白血病(acute myeloid leukemia, AML) 约占儿童急性白血病的20%.随着强化的化疗、造血干细胞移植(HSCT)及支持疗法的改进,AML的预后已得到显著改善,在过去的20年中,5年生存率已上升至60%[1].患儿的核型和对诱导化疗的反应已在不同的研究中被证实可以作为风险组分层的条件,在随后的临床研究中已被采用.通过区分不同复发风险的患儿,让我们有依据去判断是否应在第一次完全缓解(CR1)时做异基因造血干细胞移植(allo-HSCT),更好地平衡移植治疗的相关死亡(TRM).     

Acute myeloid leukemia

Acute myeloid leukemia (AML) is a heterogeneous group of leukemias that result from clonal transformation of hematopoietic precursors through the acquisition of chromosomal rearrangements and multiple gene mutations. As a result of highly collaborative clinical research by pediatric cooperative cancer groups worldwide, disease-free survival has improved significantly during the past 3 decades. Further improvements in outcomes of children who have AML probably will reflect continued progress in understanding the biology of AML and the concomitant development of new molecularly targeted agents for use in combination with conventional chemotherapy drugs.     

Acute myeloid leukemia in children: Current status and future directions

Acute myeloid leukemia (AML) accounts for 25% of pediatric leukemia and affects approximately 180 patients annually in Japan. The treatment outcome for pediatric AML has improved through advances in chemotherapy, hematopoietic stem cell transplantation (HSCT), supportive care, and optimal risk stratification. Currently, clinical pediatric AML studies are conducted separately according to the AML subtypes: de novo AML, acute promyelocytic leukemia (APL), and myeloid leukemia with Down syndrome (ML‐DS). Children with de novo AML are treated mainly with anthracyclines and cytarabine, in some cases with HSCT, and the overall survival (OS) rate now approaches 70%. Children with APL are treated with an all‐trans retinoic acid (ATRA)‐combined regimen with an 80–90% OS. Children with ML‐DS are treated with a less intensive regimen compared with non‐DS patients, and the OS is approximately 80%. HSCT in first remission is restricted to children with high‐risk de novo AML only. To further improve outcomes, it will be necessary to combine more accurate risk stratification strategies using molecular genetic analysis with assessment of minimum residual disease, and the introduction of new drugs in international collaborative clinical trials.     

Successful umbilical cord blood hematopoietic stem cell transplantation in pediatric patients with MDS/AML associated with underlying GATA2 mutations: two case reports and review of literature

Germline GATA2 mutations have been associated with a vast array of clinical manifestations, as well as hematological deficiencies and a propensity to AML or MDS. We present two cases of pediatric AML/MDS with underlying GATA2 mutations who underwent a successful umbilical cord hematopoietic stem cell transplantation using two different conditioning regimens. These cases illustrate the importance of recognizing the clinical features associated with GATA2 mutations and performing the appropriate molecular testing. Diagnosis of heritable gene mutations associated with familial AML/MDS has significant clinical implication for the patients and affected families.     

Low‐dose azacitidine maintenance therapy after allogeneic stem cell transplantation for high‐risk pediatric acute myeloid leukemia

The dismal prognosis of pediatric acute myeloid leukemia (AML) relapsing after hematopoietic stem cell transplantation (HSCT) requires exploration of novel strategies to prevent relapse. Azacitidine (AZA) maintenance therapy could potentially reduce the recurrence rate post HSCT. Here, we presents the cases of three children with high‐risk AML post HSCT who were treated with low‐dose AZA maintenance therapy, demonstrating the feasibility of this therapy. Currently, all three are in complete remission for 13–41 months despite their high‐risk characteristics. Our encouraging data warrant larger prospective studies to assess the efficacy and safety of low‐dose AZA maintenance therapy post HSCT for pediatric patients with high‐risk AML.     

Expression of vascular endothelial growth factor receptor 3 and Tie1 tyrosine kinase receptor on acute leukemia cells

BACKGROUND: Recent data indicate a role for angiogenesis in hematologic malignancies. In addition to promoting new vessel growth in the bone marrow microenvironment, angiogenic factors are regulators of both hematopoietic and leukemic cells. Activation of vascular endothelial growth factor receptor 3 (VEGFR-3) and Tie1 tyrosine kinase receptor are known to promote leukemia cell survival. The details of this complex angiogenesis-related interaction are still uncertain. PROCEDURE: We studied bone marrow samples from 73 patients with acute lymphoblastic (ALL) or myelogenous (AML) leukemia by using immunological methods. RESULTS: Vascular endothelial growth factor receptor 3 expression was found in 15% of the samples, particularly in samples with pediatric lymphoblastic leukemias and monocytic AMLs. Tie1 protein expression was found in 11% of the samples, all of which were from adult AML patients. CONCLUSIONS: Our findings suggest that there are angiogenesis-related differences between pediatric and adult lymphoblastic leukemias as well as between lymphoid and myeloid leukemias.     

BILATERAL EXOPHTHALMUS DUE TO RETRO-ORBITAL CHLOROMAS IN A BOY WITH t(8;21)-POSITIVE ACUTE MYELOBLASTIC LEUKEMIA

Exophthalmus is an infrequent finding in pediatrics. The differential diagnoses include chloromas, tumors of immature hematopoietic precursor cells. The case of a child with acute myeloid leukemia is reported. The presenting signs had included exophthalmus and nasal speech due to retro-orbital and sinusoidal chloromas, respectively. As in most cases of pediatric acute myeloid leukemia with chloroma, the AML1/ETO fusion gene was found, which portended a not unfavorable prognosis. This child was treated according to the AML-BFM 98 protocol and achieved an ongoing remission. The exophthalmus resolved completely.     

Bilateral exopthalmus due to retro-orbital chloromas in a boy with t(8;21)- positive acute myeloblastic acute leukemia

Exophthalmus is an infrequent finding in pediatrics. The differential diagnoses include chloromas, tumors of immature hematopoietic precursor cells. The case of a child with acute myeloid leukemia is reported. The presenting signs had included exophthalmus and nasal speech due to retro-orbital and sinusoidal chloromas, respectively. As in most cases of pediatric acute myeloid leukemia with chloroma, the AML1/ETO fusion gene was found, which portended a not unfavorable prognosis. This child was treated according to the AML-BFM 98 protocol and achieved an ongoing remission. The exophthalmus resolved completely.     

Myeloid lineage switch following chimeric antigen receptor T‐cell therapy in a patient with TCF3‐ZNF384 fusion‐positive B‐lymphoblastic leukemia

A pediatric patient diagnosed initially with B‐lymphoblastic leukemia (B‐ALL) relapsed with lineage switch to acute myeloid leukemia (AML) after chimeric antigen receptor T‐cell (CAR‐T) therapy and hematopoietic stem cell transplant. A TCF3‐ZNF384 fusion was identified at diagnosis, persisted through B‐ALL relapse, and was also present in the AML relapse cell population. ZNF384‐rearrangements define a molecular subtype of B‐ALL characterized by a pro‐B‐cell immunophenotype; furthermore, ZNF384‐rearrangements are prevalent in mixed‐phenotype acute leukemias. Lineage switch following CAR‐T therapy has been described in patients with KMT2A (mixed lineage leukemia) rearrangements, but not previously in any patient with ZNF384 fusion.     

Invasive chaetomium infection in two immunocompromised pediatric patients

The majority of fungal infections are caused by species such as Candida and Aspergillus. Other rare and emerging opportunistic fungal infections are on the increase. Risk factors for such infections include receipt of antimicrobial agents, chemotherapy, immunosuppression secondary to hematopoietic stem cell or solid organ transplantation, neutropenia, presence of indwelling intravascular catheter, prior hemodialysis, or previous fungal colonization. We present here the first 2 reports of fatal and invasive Chaetomium infections in pediatric patients. The first case occurred in a child with acute myeloid leukemia (AML) and the other in a child with hemophagocytic syndrome (HSP).