LONG-TERM FOLLOW-UP OF CHILDREN WITH ACUTE LEUKEMIA WHO UNDERWENT SCT

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。儿童干细胞移植与许多长期并发症相关，包括内分泌异常、神经认知困难、学习成绩差、骨质疏松症和心肺异常。很少有大规模的研究评估这些晚期效应在白血病治疗儿童中的发生率，特别是对三岁以下白血病移植儿童的长期并发症知之甚少。我们研究的主要目的是更好地确定SCT在婴儿期和幼儿期的长期并发症。考虑到明尼苏达大学已经进行了大量的儿童干细胞移植手术，特别是白血病儿童，以及该队列的随访时间（目前超过20年），我们有独特的能力在明尼苏达大学进行这样的研究。到目前为止，还没有一项研究以前瞻性、随机的方式系统地评估SCT幸存者。该方法将消除(1)根据可获得的保险覆盖范围来选择受试者以支付长期随访的费用，(2)患者家庭的经济资源返回该机构进行持续随访，(3)以及有后期影响的患者优先参与的潜在选择偏差。这将是一项针对ALL或AML儿童的队列研究，这些儿童在不到10岁时在明尼苏达大学接受了SCT，并且存活了至少一年。潜在的受试者将包括明尼苏达大学SCT数据库中现有的(1)All或AML患者的总数，这些患者(2)在移植时<10年，(3)在SCT后存活bb0或= 1年，目前处于缓解期。研究人员将与受试者联系，向其解释研究内容并邀请其参与。所有参与的费用，包括旅行和住宿将由研究承担，因此参与者的时间将是他们参与的唯一“成本”。这项研究将在明尼苏达大学的普通临床研究中心进行。受试者将接受全面的神经心理学和神经内分泌/代谢评估。GCRC将提供检查空间、护理和实验室绘图支持以及DEXA扫描。体格检查时，由护理人员和医生测量身高、体重、Tanner分期（青春期发育）和体重/身高。实验室评估将包括内分泌功能的测量，包括甲状腺功能（T4和TSH）和性腺功能[FSH， LH]，骨代谢（吸收/形成）的代谢参数，包括钙、镁、磷、骨钙素、骨特异性碱性磷酸酶、尿n -端肽，以及其他代谢参数，包括脂质谱、空腹胰岛素和葡萄糖，肾功能的标准测量(BUN/肌酐，UA)和肝功能检查。所有受试者将接受DEXA扫描以评估骨密度，以及骨龄x线（女性>9岁及以下，男性>10岁及以下）。在完成体格检查和血液检查后，所有受试者将由同一名儿科神经心理学家进行适合年龄的神经心理学评估。本研究中使用的神经心理测试的所有组成部分都是标准化的，特定于年龄的（并且在不同年龄之间具有可比性），并将评估广泛的神经认知和功能领域。父母（或目前年龄超过10岁的患者）将被要求完成一份调查问卷，评估任何移植相关的医学晚期效应的发生和生活质量的评估（City of Hope BMT QOL, SF-36，或儿童健康问卷，取决于受试者的年龄）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Stem cell transplantation in childhood has been associated with many long-term complications in cluding endocrine abnormalities, neurocognitive difficulties, poor school performance, osteoporosis, and cardiopulmonary abnormalities. Few large-scale studies have evaluated the incidence of these late effects in children treated for leukemia, and specifically very little is known about the long-term complications in children transplanted for leukemia at less than three years of age. The primary objective of our research will be to better define the long-term complications of SCT in infancy and very young childhood. We are uniquely able to perform such a study here at the University of Minnesota given the large number of pediatric stem cell transplants that have been performed at this institution, particularly for children wih leukemia, and the length of follow-up that is available on this cohort (now over 20 year). To date, there has not been a study that has systematically evaluated SCT survivors in a prospective, randomized fashion. This method will eliminate the bias of (1) subject selection based upon the availability of insurance coverage to cover the costs of long-term follow-up, (2) financial resources of a patient of family to return to this institution for ongoing follow-up, (3) and the potential selection bias of preferential participation by patients that have experienced late effects. This will be a cohort study of children with ALL or AML who a SCT at the University of Minesota when they were less than ten years of age, and have survived at least one year. Potential subjects will include the total existing number of subjects in the University of Minnesota SCT database with (1) All or AML who were (2) <10 years at the time of transplant and (3) have survived > or = 1 year post-SCT currently in remission. Subjects will be contacted by the investigators to explain the study and offer participation. All costs of participation, including travel and lodging will be borne by the study so that participant time will be the only "cost" of their participation. The study will take place in the General Clinical Research Center at the University of Minnesota. Subjects will undergo full neuropsychological and neuroendocrine/metabolic evaluation. The GCRC would provide exam space, nursing and lab draw support, and DEXA scanning. Measurement of height, weight, Tanner Staging (pubertal development) and body weight/height will be obtained at the time of the physical examination by nursing staff physicians. Laboratory assessment will in clude measures of endocrinologica functions including thyroid function (T4 and TSH) and gonadal function [FSH, LH, Metabolic parameters of bone metabolism (resorption/formation) including calcium, magnesium, phosphorus, osteocalcin, bone specific alkaline phosphatase, urinary N-telopeptide, and additional metabolic parameters including lipid profile, fasting insulin and glucose, standard measures of renal function (BUN/creatinine, UA) and liver function tests would be performed. All subjects will undergo DEXA scanning for evaluation of bone mineral density, as well as bone age x-rays (for females>9 and <19, males >10 and <18). After completion of physical exam and blood work, all subjects will undergo an age appropriate neuropsychological evaluation administeres by the same pediatric neuropsychologist. All components of this neuropsychological testing to be utilized for this study are standardized, age specific (and comparable across different ages) and will assess a wide range of neurocognitive and functional domains. Parents (or patients if presently older than 10 years of age) will be asked to complete a questionnaire that will assess the occurrence of any transplant related medical late effects and an assessment of quality of life (City of Hope BMT QOL, SF-36, or Child Health Questionnaire, depending on subject age).