PEDIATRIC HYDROXYUREA STUDY GROUP

羟基脲（HU）是一种已被证明 在一个小实验组中增加胎儿血红蛋白产生， 患有镰状细胞病（SCD）的成年受试者。 因为这些研究 已经揭示了血红蛋白F反应在成人中具有最小的毒性， 一项更大规模的安慰剂对照成人疗效研究， 正在进行中 直到HU疗法对SCD的疗效在 在成人试验中，没有理由进行大规模的有效性研究， 在儿童镰状细胞病患者中进行的试验。 然而，有一个小 全国儿童和青少年的人数， 目前没有可用的治疗方案。 这些都是非典型儿童 痛苦的“危机”发生率极高， 胸部综合征或中风发作，以及无法输血 因为同种免疫。 在大多数大型儿科中心， 将考虑对此类患者进行“同情”治疗， 个人基础。 我们感到关切的是，虽然这些个别特设 协议可能被证明有利于治疗个别患者， 没有集体的知识，没有有组织的数据可以借鉴 如果需要设计一项大型前瞻性试验， 儿童的临床疗效。 在本提案中，我们组织了一个 儿科临床研究者联盟，他们同意不使用 各种特设协议来治疗他们的病人，但相反， 遵循一个共同的协议，并汇集他们的个人经验。 我们 不打算增加儿科患者的数量， 但是，我们应该让所有这些患者接受治疗， 统一的方式。 已确定入选和排除标准。 一系列标准 已编制了数据收集表格。 数据协调中心 将设在杜克大学镰状细胞中心。 给药时间表和 毒性标准基于成人经验的结果。 患者将从15 mg/kg/天开始，并以5 mg/kg的增量推进 每12周一次，遵循严格的毒性标准。 最大剂量 将为30 mg/kg/天。 患者将每两周接受一次监测。 F 细胞计数将在约翰霍普金斯医学中心集中测定 学校由医学博士乔治多佛。 一旦“最大耐受剂量”达到 患者将继续使用该剂量12个月。 我们的目标是获得以下问题的初步数据：（1） 羟基脲能有效增加胎儿血红蛋白水平吗？ 儿童，（2）是否有严重的毒性，在儿童中没有看到 在成人中，和（3）什么是对生长的影响，羟基脲治疗？ 总体策略是制定一个共同的给药方案， 排除标准和监测方案。

Hydroxyurea (HU) is an antineoplastic agent that has been shown to increase fetal hemoglobin production in a small experimental group of adult subjects with sickle cell disease (SCD). Because these studies have revealed a hemoglobin F response with minimal toxicity in adults, a larger-scale, placebo controlled study of efficacy in adults is underway. Until the efficacy of HU therapy for SCD is demonstrated in the adult trial, there is no rationale for doing a large scale efficacy trial in pediatric sickle cell patients. However, there are a small number of children and adolescents around the country for whom there is currently no treatment option available. These are atypical children with exceptionally high rates of painful "crises", severe recurrent episodes of chest syndrome, or stroke, and the inability to be transfused because of alloimmunization. In most large pediatric centers, a trial of hydroxyurea will be considered for such patients on a "compassionate" individual basis. We are concerned that although these individual ad hoc protocols may prove beneficial to treat individual patients, there will be no collective knowledge gained, no organized body of data to draw from if and when it comes time to design a large prospective trial assessing clinical efficacy in children. In this proposal, we organize a consortium of pediatric clinical investigators who will agree not to use a variety of ad hoc protocols to treat their patients, but will instead follow a common protocol and pool their individual experiences. We do not intend to increase the number of pediatric patients who would receive hydroxyurea, but rather to have all of these patients treated in a uniform manner. Entry and exclusion criteria have been defined. A series of standard data collection forms have been developed. The data coordinating center will be based at Duke-UNC Sickle Cell Center. The dosing schedule and toxicity criteria are based on the results of the adult experience. Patients will start on 15 mg/kg/day and be advanced in 5 mg/kg increments every 12 weeks, following strict toxicity criteria. The maximal dose will be 30 mg/kg/day. Patients will be monitored every two weeks. F cell counts will be determined centrally at the Johns Hopkins Medical School by George Dover, M.D. Once the "maximal tolerated dose" is achieved, patients will be continued on that dose for 12 months. Our goal is to obtain preliminary data on the following questions: (1) is hydroxyurea effective in increasing fetal hemoglobin levels in children, (2) are there serious toxicities in children that were not seen in adults, and (3) what is the impact of hydroxyurea therapy on growth? The overall strategy would be to develop a common dosing schedule, exclusion criteria, and monitoring protocol.