Myositis complicating viridans streptococcal sepsis in childhood leukemia

Hematogenous focal infections are a rare complication of bacteremia or sepsis caused by viridans-group streptococci. We describe two patients with acute leukemia who developed myositis during alpha-hemolytic streptococcal bacteremia. Children complaining of severe muscle pain associated with viridans streptococcal infections should be carefully evaluated for the presence of focal pyogenic complications and rhabdomyolysis. The severity of infectious myositis is highly variable, depending on the etiologic organism and host immunity, making individualized treatment the most effective approach.     

Epidemiology of childhood acute myeloid leukemia

Although leukemia is the most common childhood cancer diagnosis, the subtype, acute myeloid leukemia (AML), is less common and fewer etiologic studies exist. This review summarizes the major risk factors for AML. We searched the literature using PubMed for articles on childhood AML and reviewed 180 articles. While few risk factors are definitive, we identified several with consistent evidence of a possible effect. Thorough analysis of genetic and epigenetic factors is missing from this literature and methodological issues are unresolved. Future studies should more closely examine causal mechanisms, improve exposure measurement, and include analysis using genetic and epigenetic factors. Pediatr Blood Cancer 2013; 60: 728–733. © 2013 Wiley Periodicals, Inc.     

Characteristics and outcome in patients with central nervous system involvement treated in European pediatric acute myeloid leukemia study groups

1 Background

There is no consensus on the treatment for pediatric patients with acute myeloid leukemia and initial central nervous system (CNS) involvement.

2 Methods

To evaluate different CNS‐directed treatment options (intrathecal [IT] therapy, CNS irradiation, hematopoietic stem cell transplantation [HSCT]), 261 patients (excluding acute promyelocytic leukemia) with initial CNS involvement treated in trials with similar intensive chemotherapy by four cooperative European study groups (1998–2013) were studied and compared with CNS‐negative patients from the Berlin–Frankfurt–Münster group.

3 Results

Patient characteristics in the different study groups were comparable. Young age, high white blood cell count, extramedullary involvement other than the CNS, monoblastic morphology, and inv(16) were associated with CNS involvement (each P < 0.0001). There were no major differences in outcome between the study groups. The cumulative incidence of relapse (CIR) regarding the CNS was higher in initially CNS‐positive versus initially CNS‐negative patients (all: 8 ± 2% vs. 3 ± 1%, P_(Gray) = 0.001; isolated: 4 ± 1% vs. 1 ± 0%, P_(Gray) = 0.03). However, global outcome of the CNS‐positive cohort (overall survival, 64 ± 3%; event‐free survival 48 ± 3%; and CIR 33% ± 3%) did not differ significantly from CNS‐negative patients. Risk groups defined by cytogenetics were of likewise prognostic significance in CNS‐positive and ‐negative patients. CNS treatment with cranial irradiation was not superior compared to IT therapy and systemic chemotherapy (± HSCT).

4 Conclusion

Although CNS relapses occurred more frequently in initially CNS‐positive patients, their global outcome was similar as in CNS‐negative patients. Intensified IT therapy was heterogeneous; however, at least eight applications, preferably with triple IT chemotherapy, seem to be appropriate to accompany dose‐intensive systemic chemotherapy.     

Hematopoietic stem cell transplantation in pediatric patients with acute myeloid leukemia without favorable cytogenetics

Intensified chemotherapy, HSCT, and supportive care improve the survival of pediatric patients with AML. However, no consensus has been reached regarding the role of HSCT in patients without favorable cytogenetics. We evaluated OS and EFS according to prognostic factors that affect clinical outcomes, including cytogenetics risk group, conditioning regimen, donor type, disease status at the time of HSCT, and number of chemotherapy cycles prior to HSCT in 65 pediatric patients with AML without favorable cytogenetics who underwent HSCT. Fifteen of the 65 patients died: three of TRM and 12 of disease‐related mortality. The 5‐year OS and EFS were 78.0% and 72.0%, respectively, and the 5‐year cumulative relapse and TRM rates were 26.9% and 5.1%, respectively. Survival rates were not influenced by cytogenetic group (intermediated vs. poor), donor type (related vs. unrelated), transplant type (myeloablative vs. reduced‐intensity conditioning), or number of pretransplant chemotherapy cycles (≤3 vs. >3 cycles). The low TRM rate and encouraging outcomes suggest that HSCT may be a feasible treatment for pediatric patients with AML without favorable cytogenetics.     

儿童急性髓系白血病治疗相关进展

经过近40年的发展,儿童髓系白血病的生存率显著上升。生存率的增长有赖于以下因素:对细胞遗传学及早期治疗反应等预后危险因素更深刻的认知,对疾病危险分组更为准确;化疗方案的优化,包括化疗剂量的强化、传统诱导化疗天数的延长等;新型化疗药物,如靶向药物的出现;造血干细胞移植的进展。文章主要综述以上各因素的研究进展。[临床儿科杂志,2012,30(5):487-491]     

Development of acute lymphoblastic leukemia following treatment for acute myeloid leukemia in children with Down syndrome: A case report and retrospective review of Children's Oncology Group acute myeloid leukemia trials

Children with Down syndrome have a 150‐fold increased risk of developing acute myeloid leukemia (AML) and 20‐fold increased risk of developing acute lymphoblastic leukemia (ALL). Although the risk of developing AML and ALL is significantly increased in children with Down syndrome, the development of both malignancies in the same patient is very rare. We describe a patient with Down syndrome who developed ALL 6 years after being diagnosed with AML. We performed a literature review and Children's Oncology Group query and discovered eight published cases and five cases of ALL following AML in pediatric patients with Down syndrome, as well as six cases of ALL following AML in non‐Down syndrome patients. There was a similar cumulative incidence of ALL after treatment for AML in the Down syndrome and non‐Down syndrome populations. Overall survival in patients with Down syndrome who developed ALL after treatment for AML was comparable to overall survival for patients with Down syndrome with de novo ALL with an average follow‐up of 7 years after ALL diagnosis. Clinical data collected were used to discuss whether this phenomenon represents a secondary leukemia, second primary cancer, or mixed‐lineage leukemia.     

ras基因与儿童急性髓细胞性白血病关系研究

目的探讨ras基因在儿童急性髓细胞性白血病（AML）中的表达及其与治疗和预后的相关性。方法用逆转录聚合酶链反应（RT—PCR）半定量方法检测ras基因家族（K—ras,N—ras,H—ras）的表达水平,结合细胞形态学、流式细胞仪免疫分型检测、染色体R带显带核型分析,对36例初诊AML及部分病例进行跟踪。同期采集30例特发性急性血小板减少性紫癜（ITP）患儿骨髓标本作为对照。结果实验组与对照组相比。N-ras、K—ras的平均表达水平明显升高,差异有统计学意义,其中N—ras更具显著意义。AML患儿中ras基因突变多见于M2、M4及M5型。对2例M2患儿进行跟踪检测（1例为不同时期包括初诊和缓解期及复发前的测定,另1例为长期无病生存）,ras基因水平异常活化可见于复发前,也可见于长期缓解患儿。结论初诊儿童AMLras基因表达水平异常增高。ras检测可作为判断儿童AML疗效、预后及随访指标之一。     

Acute lymphoblastic leukemia in patients with Down syndrome with a previous history of acute myeloid leukemia

Patients with Down syndrome (DS) are predisposed to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in early and later childhood, respectively, but rarely experience both. We herein discuss four patients with DS with ALL and a history of AML who were treated with various chemotherapies, one of whom later received a bone marrow transplantation. Three patients survived and remain in remission. One patient died of fulminant hepatitis during therapy. No common cytogenetic abnormalities in AML and ALL besides constitutional +21 were identified, indicating that the two leukemia types were independent events. However, the underlying pathomechanism of these conditions awaits clarification.     

Bilateral internal carotid artery occlusions in a pediatric patient with refractory acute myeloid leukemia

Thromboembolism is a well‐known complication of cancer including acute myeloid leukemia (AML) especially in patients with high myeloblast counts. However, spontaneous vaso‐occlusion in the main arteries is very rare especially in patients with low blast counts and no pre existing vasculopathy. We report the case of a 3‐year‐old male with refractory AML who developed spontaneous bilateral internal carotid artery occlusion with diffuse cerebral infarcts. Strokes are rarely secondary to spontaneous carotid artery thrombosis and few cases have been reported in the literature. Pediatr Blood Cancer 2010;54:770–772. © 2010 Wiley‐Liss, Inc.     

儿童急性髓系白血病中miR-196b表达及预后意义

目的通过检测miR-196b在初诊急性髓系白血病(AML)患儿中的表达,评估miR-196b在儿童AML中的临床意义。方法从标本库中抽取52例初诊AML患儿骨髓,利用q RT-PCR方法检测miR-196b表达水平(结果以2-ΔΔCt表示),并与同期30例非白血病患儿标本对照。结果单核系组(M4、M5)的miR-196b表达水平高于非单核系组(M1、M2、M3、M6、M7)和对照组,而非单核系组低于对照组,差异均有统计学意义(P0.01)。miR-196b表达水平在t(15;17)组最低,11q23(MLL)组最高,差异有统计学意义(P0.01)。使用NCCN2013预后分组标准,预后良好组miR-196b表达低于预后不良组,差异有统计学意义(P0.01)。首疗程缓解组miR-196b表达明显低于首疗程未缓解组,差异有统计学意义(P0.05)。WBC≥100×109/L组miR-196b表达水平高于WBC100×109/L组,差异有统计学意义(P0.01)。miR-196b表达水平与初诊时血小板计数呈显著正相关(r=0.302,P=0.030)。结论 miR-196b表达水平在初诊AML预后不良组明显增高,高水平的miR-196b与低缓解率和较差的预后相关。miR-196b有望成为AML患儿治疗新靶点。     

白血病患儿中性粒细胞缺乏合并草绿色链球菌脓毒症临床分析

目的 了解儿童白血病中性粒细胞缺乏合并草绿色链球菌脓毒症的危险因素及临床特征.方法 回顾分析111例白血病中性粒细胞缺乏合并脓毒症患儿的临床资料.结果 111例患儿共发生136例次脓毒症,检测到138株菌株,其中25株为草绿色链球菌.25例次草绿色链球菌脓毒症中,男12例次、女13例次,脓毒症发生时中位年龄98(66～...