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Abstract：
BACKGROUND: P47phox (neutrophil cytosolic factor-1) deficiency is the most common cause of autosomal recessive chronic granulomatous disease (CGD) and is considered to be associated with a milder clinical phenotype. Allogeneic hematopoietic cell transplantation (HCT) for p47phox CGD is not well-described.
OBJECTIVE: We sought to study HCT for p47phox CGD in North America.
METHODS: Thirty patients with p47phox CGD who received allogeneic HCT at Primary Immune Deficiency Treatment Consortium centers since 1995 were included.
RESULTS: Residual oxidative activity was present in 66.7% of patients. In the year before HCT, there were 0.38 CGD-related infections per person-years. Inflammatory diseases, predominantly of the lungs and bowel, occurred in 36.7% of the patients. The median age at HCT was 9.1 years (range 1.5-23.6 years). Most HCTs (90%) were performed after using reduced intensity/toxicity conditioning. HCT sources were HLA-matched (40%) and -mismatched (10%) related donors or HLA-matched (36.7%) and -mismatched (13.3%) unrelated donors. CGD-related infections after HCT decreased significantly to 0.06 per person-years (P = .038). The frequency of inflammatory bowel disease and the use of steroids also decreased. The cumulative incidence of graft failure and second HCT was 17.9%. The 2-year overall and event-free survival were 92.3% and 82.1%, respectively, while at 5 years they were 85.7% and 77.0%, respectively. In the surviving patients evaluated, ≥95% donor myeloid chimerism at 1 and 2 years after HCT was 93.8% and 87.5%, respectively.
CONCLUSIONS: Patients with p47phox CGD suffer from a significant disease burden that can be effectively alleviated by HCT. Similar to other forms of CGD, HCT should be considered for patients with p47phox CGD.
OBJECTIVE: We sought to study HCT for p47phox CGD in North America.
METHODS: Thirty patients with p47phox CGD who received allogeneic HCT at Primary Immune Deficiency Treatment Consortium centers since 1995 were included.
RESULTS: Residual oxidative activity was present in 66.7% of patients. In the year before HCT, there were 0.38 CGD-related infections per person-years. Inflammatory diseases, predominantly of the lungs and bowel, occurred in 36.7% of the patients. The median age at HCT was 9.1 years (range 1.5-23.6 years). Most HCTs (90%) were performed after using reduced intensity/toxicity conditioning. HCT sources were HLA-matched (40%) and -mismatched (10%) related donors or HLA-matched (36.7%) and -mismatched (13.3%) unrelated donors. CGD-related infections after HCT decreased significantly to 0.06 per person-years (P = .038). The frequency of inflammatory bowel disease and the use of steroids also decreased. The cumulative incidence of graft failure and second HCT was 17.9%. The 2-year overall and event-free survival were 92.3% and 82.1%, respectively, while at 5 years they were 85.7% and 77.0%, respectively. In the surviving patients evaluated, ≥95% donor myeloid chimerism at 1 and 2 years after HCT was 93.8% and 87.5%, respectively.
CONCLUSIONS: Patients with p47phox CGD suffer from a significant disease burden that can be effectively alleviated by HCT. Similar to other forms of CGD, HCT should be considered for patients with p47phox CGD.
摘要：
背景：P47phox缺乏症是常染色体隐性慢性肉芽肿病（CGD）的最常见原因，被认为与较温和的临床表型有关。p47phoxCGD的异基因造血细胞移植（HCT）尚未得到很好的描述。
目的：研究北美p47phoxCGD的HCT。
方法：纳入了自1995年以来在初级免疫缺陷治疗联盟（PIDTC）中心接受同种异体HCT治疗的30例p47phoxCGD患者。
结果：66.7%的患者存在残余氧化活性。在HCT的前一年，有0.38个CGD相关感染/人年.炎症性疾病,主要是肺部和肠道，发生在36.7％的患者中。HCT的中位年龄为9.1岁（范围1.5-23.6岁）。大多数HCTs(90%)在使用降低的强度/毒性调节后进行。HCT来源是HLA匹配（40％）和不匹配（10％）相关的供体，或HLA匹配（36.7％）和不匹配（13.3％）的无关供体。HCT后CGD相关感染显着降低至0.06/人年（p=0.038）。炎症性肠病的频率和类固醇的使用也减少。移植物失败和第二次HCT的累积发生率为17.9％。2年总生存率和无事件生存率分别为92.3%和82.1%，分别,而在5年时，他们分别是85.7%和77.0%，分别。在评估的幸存患者中，>95%供者骨髓嵌合在1年和2年后HCT分别为93.8%和87.5%，分别。
结论：p47phoxCGD患者具有显著的疾病负担，可以通过HCT有效缓解。类似于其他形式的CGD，对于p47phoxCGD患者应考虑HCT。
目的：研究北美p47phoxCGD的HCT。
方法：纳入了自1995年以来在初级免疫缺陷治疗联盟（PIDTC）中心接受同种异体HCT治疗的30例p47phoxCGD患者。
结果：66.7%的患者存在残余氧化活性。在HCT的前一年，有0.38个CGD相关感染/人年.炎症性疾病,主要是肺部和肠道，发生在36.7％的患者中。HCT的中位年龄为9.1岁（范围1.5-23.6岁）。大多数HCTs(90%)在使用降低的强度/毒性调节后进行。HCT来源是HLA匹配（40％）和不匹配（10％）相关的供体，或HLA匹配（36.7％）和不匹配（13.3％）的无关供体。HCT后CGD相关感染显着降低至0.06/人年（p=0.038）。炎症性肠病的频率和类固醇的使用也减少。移植物失败和第二次HCT的累积发生率为17.9％。2年总生存率和无事件生存率分别为92.3%和82.1%，分别,而在5年时，他们分别是85.7%和77.0%，分别。在评估的幸存患者中，>95%供者骨髓嵌合在1年和2年后HCT分别为93.8%和87.5%，分别。
结论：p47phoxCGD患者具有显著的疾病负担，可以通过HCT有效缓解。类似于其他形式的CGD，对于p47phoxCGD患者应考虑HCT。
