严重联合免疫缺陷(SCID)是原发性免疫缺陷患者小儿造血细胞移植(HCT)的最常见适应症之一。历史上,在出生后第一年内出现机会性感染的婴儿中诊断出SCID。在美国大部分地区进行SCID的新生儿筛查(NBS),现在,大多数患有SCID的婴儿在出生后的前3.5个月内得到诊断和治疗;然而,在世界其他地方,缺乏NBS意味着大多数SCID婴儿仍存在感染.目前接受移植的SCID患者在移植后3年的平均生存率>70%。尽管这可能因多种因素而有很大差异,包括移植时的年龄和感染状况,使用的供体来源类型,移植前的移植物操作,移植物抗宿主病预防,使用的调理类型(如果有),和潜在的SCID基因型。在至少一项SCID患者的研究中,移植后8.7年(范围为26年)的长期生存率为77%.尽管大多数SCID患者会在没有任何预处理疗法的情况下移植T细胞,根据基因型,捐助者来源,HLA匹配,和循环母体细胞的存在,其中相当大的百分比将无法实现完全的免疫重建。没有条件,T细胞重建通常发生,虽然并不总是完全,而B细胞移植没有,留下一些分子类型的SCID患者具有内在缺陷的B细胞,在大多数情况下,依赖于定期输注免疫球蛋白。正因为如此,许多中心已经使用烷化剂进行调理,包括白消安或美法仑,这些烷化剂可以打开骨髓壁ches,以尝试实现B细胞重建。因此,我们必须了解这些药物在该患者人群中的潜在晚期效应.还有与SCID的HCT相关的非免疫学风险似乎取决于患者的基因型。在这份报告中,我们评估了已发表的关于晚期效应的数据,并试图总结与条件和替代供体来源相关的已知风险.这些数据,虽然信息丰富,这也清楚地表明,就HCT后的结果而言,SCID人群还有很多需要学习的东西。本文将总结当前的发现,并建议在被认为是高度优先的领域进行进一步的研究。关于建议的长期后续行动方法的具体准则,包括实验室和临床监测,将在随后的论文中发表。
Severe combined immunodeficiency (SCID) is 1 of the most common indications for pediatric hematopoietic cell transplantation (HCT) in patients with primary immunodeficiency. Historically, SCID was diagnosed in infants who presented with opportunistic infections within the first year of life. With newborn screening (NBS) for SCID in most of the United States, the majority of infants with SCID are now diagnosed and treated in the first 3.5 months of life; however, in the rest of the world, the lack of NBS means that most infants with SCID still present with infections. The average survival for SCID patients who have undergone transplantation currently is >70% at 3 years after transplantation, although this can vary significantly based on multiple factors, including age and infection status at the time of transplantation, type of donor source utilized, manipulation of graft before transplantation, graft-versus-host disease prophylaxis, type of conditioning (if any) utilized, and underlying genotype of SCID. In at least 1 study of SCID patients who received no conditioning, long-term survival was 77% at 8.7 years (range out to 26 years) after transplantation. Although a majority of patients with SCID will engraft T cells without any conditioning therapy, depending on genotype, donor source, HLA match, and presence of circulating maternal cells, a sizable percentage of these will fail to achieve full immune reconstitution. Without conditioning, T cell reconstitution typically occurs, although not always fully, whereas B cell engraftment does not, leaving some molecular types of SCID patients with intrinsically defective B cells, in most cases, dependent on regular infusions of immunoglobulin. Because of this, many centers have used conditioning with alkylating agents including busulfan or melphalan known to open marrow niches in attempts to achieve B cell reconstitution. Thus, it is imperative that we understand the potential late effects of these agents in this patient population. There are also nonimmunologic risks associated with HCT for SCID that appear to be dependent upon the genotype of the patient. In this report, we have evaluated the published data on late effects and attempted to summarize the known risks associated with conditioning and alternative donor sources. These data, while informative, are also a clear demonstration that there is still much to be learned from the SCID population in terms of their post-HCT outcomes. This paper will summarize current findings and recommend further research in areas considered high priority. Specific
guidelines regarding a recommended approach to long-term follow-up, including laboratory and clinical monitoring, will be forthcoming in a subsequent paper.