RDSafe: A Multi-Institutional Study of HSC Donor Safety and Quality Life

描述（由申请人提供）：2006年，北美有8,000多名成人和儿童捐献骨髓（BM）或外周血干细胞（PBSC）用于造血干细胞（HSC）移植。这些捐赠中的大多数来自接受者的亲属（5000/年），由照顾该接受者的移植中心提供便利。其余的捐赠来自不相关的匿名成年志愿者，由国家骨髓捐赠者计划（NMDP）协调和仔细管理。在过去的二十年里，通过NMDP进行的高质量研究已经产生了大量与无关HSC捐赠相关的医学和心理毒性数据。相反，关于相关供体（RD）的医疗和心理安全性的前瞻性、可量化和易于比较的数据要么已经过时，要么缺乏，特别是在儿科和老年供体（> 60岁）的潜在弱势人群中。我们提出的研究（称为RDSafe，相关供体安全性研究）通过使用NMDP开发的复杂和全面的数据工具比较相关HSC供体与无关供体（UD）的医学和心理毒性，填补了这一关键数据空白。将使用常见（改良CTC标准）和不常见事件的标准量表报告急性毒性。将使用经过充分验证的标准化健康相关生活质量（HRQoL）工具（成人SF-36和儿童PedsQL-4.0）评估供体，并与年龄匹配的正常人和相关与无关供体进行比较。本研究由国际血液和骨髓移植研究中心（CIBMTR）供体健康与安全工作委员会成员开发：本提案的PI是该委员会的现任联合主席。NMDP的供体安全性经验和数据工具将与CIBMTR的血液和骨髓移植临床研究资源（RCI-BMT）提供的统计专业知识相结合。本研究旨在增加儿科和老年RD的累积，以收集足够的数据来提供这些人群的特定毒性风险特征。来自儿童肿瘤组的40家CIBMTR移植中心和80多家儿科移植中心已承诺招募RD。该队列将与在70多个NMDP供体中心收集的同时入组的UD队列进行比较。在其他重要贡献中，从RDSafe研究中收集的信息将1）定义RD与UD的医学和心理结局差异，并将其与年龄匹配的正常人进行比较，2）将RD人群划分为低风险和高风险类别，识别供体的弱势人群，3）描述所有年龄段RD中BM与PBSC捐献的风险差异，（4）确定RD知情同意的标准;（5）确定捐赠者是否存在因捐赠而受到严重伤害的医疗或心理风险。公共卫生相关性：有关骨髓或外周血干细胞供体安全性的现有研究提供的信息不足以理解医疗和心理风险，特别是在儿童和60岁以上的成年人中。这项研究将仔细测量所有年龄段的相关捐赠者的罕见和常见的医疗和心理副作用，并将结果与无关捐赠者进行比较，以确定相关捐赠者是否有增加的伤害风险。

DESCRIPTION (provided by applicant): In 2006 more than 8,000 adults and children in North America donated either bone marrow (BM) or peripheral blood stem cells (PBSC) for hematopoietic stem cell (HSC) transplantation. Most of these donations came from relatives of the recipient (5000/yr), facilitated by transplant centers caring for that recipient. The remaining donations came from anonymous unrelated adult volunteers, coordinated and carefully regulated by the National Marrow Donor Program (NMDP). Over the past two decades, high quality studies run through the NMDP have resulted in a wealth of data regarding medical and psychological toxicities associated with unrelated HSC donation. Conversely, prospective, quantifiable, and readily comparable data regarding the medical and psychological safety of related donors (RDs) is either outdated or lacking, especially in the potentially vulnerable populations of pediatric and older donors (>60yrs). Our proposed study (called RDSafe, related donor safety study) fills this critical data gap by comparing medical and psychological toxicities of related HSC donors with unrelated donors (UDs) using sophisticated and comprehensive data tools developed by the NMDP. Acute toxicities will be reported using standard scales for common (Modified CTC criteria) and uncommon events. Well-validated, standardized health related quality of life (HRQoL) instruments (SF-36 for adults and PedsQL" 4.0 for children) will be used to assess donors and comparisons will be made with age- matched normals and related versus unrelated donors. The study has been developed by members of the Donor Health and Safety Working Committee of the Center for International Blood and Marrow Transplant Research (CIBMTR): the PI of this proposal is a current Co-Chair of this committee. The donor safety experience and data tools of the NMDP will be combined with statistical expertise provided by the Resource for Clinical Investigations in Blood and Marrow Transplant (RCI-BMT) of the CIBMTR. The study has been designed to enhance accrual of pediatric and older RDs, in order to gather sufficient data to provide toxicity risk profiles specific to these groups. Forty CIBMTR transplant centers and over 80 pediatric transplant centers from the Children's Oncology Group have committed to enroll RDs. This cohort will be compared to a concurrently enrolled cohort of UDs collected at over 70 NMDP donor centers. Among other significant contributions, the information gathered from the RDSafe study will 1) define differences in the medical and psychological outcomes of RDs vs. UDs and compare them with age-matched normals, 2) segment the RD population into categories of lower and higher risk, identifying vulnerable populations of donors, 3) describe differences in risk of BM vs. PBSC donation in RD of all ages, 4) define standards for informed consent of RD, and 5) identify donors who are at medical or psychological risk to be significantly harmed by donation. PUBLIC HEALTH RELEVANCE: Available studies of related bone marrow or peripheral blood stem cell donor safety provide inadequate information to understand the medical and psychological risks, especially in children and adults above age sixty. This study will take careful measurements of both rare and common medical and psychological side- effects in related donors of all ages and compare the outcomes to unrelated donors to find out if related donors are at increased risk for harm.