Pediatric Stem Cell Transplantation Program and Laboratory for Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.
Unité d'Immuno-hematologie et Rhumatologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Université de Paris, Paris, France; Institut Imagine, INSERM UMR1163, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Paris, France.
J Allergy Clin Immunol. 2022 May;149(5):1744-1754.e8. doi: 10.1016/j.jaci.2021.10.017. Epub 2021 Oct 27.
Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome.
We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome.
HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed.
Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P < .001). The 2-year event-free survival (EFS) was similar in matched and mismatched unrelated donor and less favorable in mismatched related donor (MMRD) HSCT (P < .001). Genetic subgroups did not differ in 2-year OS (P = .1) and EFS (P = .073). In multivariate analysis, pretransplantation infections and use of MMRDs were associated with less favorable OS and EFS. With a median follow-up of 6.2 years (range, 2.0-11.8 years), 73 of 152 patients in the IR cohort were alive and well without Ig dependency. IL-2 receptor gamma chain/Janus kinase 3/IL-7 receptor-deficient SCID, myeloablative conditioning, matched donor HSCT, and naive CD4 T lymphocytes >0.5 × 10/μL at +1 year were identified as independent predictors of favorable clinical and immunologic outcome.
Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.
造血干细胞移植（HSCT）是严重联合免疫缺陷（SCID）患者的一种根治性治疗方法，SCID 是一组单基因免疫疾病，否则会导致致命后果。
我们对特定于基因型的 HSCT 结果进行了全面的多中心分析，包括对免疫重建（IR）和对临床结果的预测价值进行详细分析。
我们对 2006 年至 2014 年在 SCETIDE 注册中心接受移植并经基因确认的 338 例 SCID 患者的 HSCT 结果进行了研究。在 152 例具有代表性的亚组患者中，分析了 IR 和长期临床结果的数据。
与匹配的家族和无关供体相比，2 年 OS 相似，优于不匹配供体 HSCT（P<0.001）。匹配和不匹配无关供体的 2 年无事件生存率（EFS）相似，而不匹配相关供体（MMRD）HSCT 的 EFS 较差（P<.001）。2 年 OS（P=0.1）和 EFS（P=0.073）在遗传亚组之间没有差异。多变量分析表明，移植前感染和使用 MMRD 与较差的 OS 和 EFS 相关。在中位随访 6.2 年（范围 2.0-11.8 年）后，IR 队列中 152 例患者中有 73 例存活且无需依赖 Ig。IL-2 受体γ链/Janus 激酶 3/IL-7 受体缺陷 SCID、清髓性预处理、匹配供体 HSCT 和 +1 年时幼稚 CD4 T 淋巴细胞>0.5×10/μL 被确定为临床和免疫结果良好的独立预测因素。
SCID 患者 HSCT 的最新进展导致所有基因型和供体类型的 OS 和 EFS 均得到改善。为了获得良好的长期结果，治疗策略应旨在实现最佳幼稚 CD4 T 淋巴细胞再生。
