Reduced-Intensity Conditioning Hematopoietic Cell Transplantation Is an Effective Treatment for Patients with SLAM-Associated Protein Deficiency/X-linked Lymphoproliferative Disease Type 1
Reduced-Intensity Conditioning Hematopoietic Cell Transplantation Is an Effective Treatment for Patients with SLAM-Associated Protein Deficiency/X-linked Lymphoproliferative Disease Type 1
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DOI：
10.1016/j.bbmt.2014.06.003
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发表时间：
2014-10-01
影响因子：
4.3
通讯作者：
Filipovich, Alexandra H.
中科院分区：
文献类型：
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作者：
Marsh, Rebecca A.;Bleesing, Jack J.;Filipovich, Alexandra H.
X连锁淋巴组织增生性疾病1型（XLP 1）是一种罕见的免疫缺陷引起的突变SH 2D 1A。由于与XLP 1相关的发病率和死亡率，经常进行异基因造血细胞移植（HCT）。对这些患者使用低强度预处理（RIC）方案的经验有限。在这里，我们报告了我们8年的单中心经验。2006年至2013年期间，16例诊断为XLP 1的连续患者在接受由阿仑单抗、氟达拉滨和美法仑组成的RIC方案后接受了同种异体HCT。患者表型包括EB病毒（n = 5）或人疱疹病毒6（n = 1）后噬血细胞性淋巴组织细胞增多症（HLH）、巨噬细胞活化综合征（n = 1）、间质性肺炎和脑炎（n = 1）、B细胞淋巴瘤（n = 8）和低丙种球蛋白血症（n = 2）。一名患者无症状。16例患者中有14例接受了8/8例HLA匹配的无关或相关骨髓移植，而2例患者接受了不匹配的无关移植。急性移植物抗宿主病（GVHD）的预防包括甲基强的松龙和环孢素，除了1例患者，谁额外接受甲氨蝶呤。所有患者均恢复造血功能。无肝静脉闭塞性疾病或肺出血病例。1例患者（6%）发生急性GVHD，随后也发生慢性GVHD（6%）。5例患者（31%）出现混合嵌合体。只有1例混合嵌合体患者（6%）的供体嵌合体下降至50%以下，但在输注供体淋巴细胞和CD 34（+）选择性干细胞加强后恢复至完全供体嵌合体。感染并发症频繁，特别是病毒再激活。Kaplan-Meier分析估计的一年生存率为80%，长期生存率估计为71%。有或无HLH病史的患者生存率相似（分别为86%和75%，P = 0.70）。HCT后未发生淋巴瘤或HLH。RIC HCT联合阿仑单抗、氟达拉滨和美法仑是XLP 1患者的有效治疗，无论既往疾病表现如何（包括HLH），均提供良好的生存率。2014年美国血液和骨髓移植协会。
X-linked lymphoproliferative disease type 1 (XLP1) is a rare immune deficiency caused by mutations in SH2D1A. Allogeneic hematopoietic cell transplantation (HCT) is often performed because of the morbidity and mortality associated with XLP1. There is limited experience using reduced-intensity conditioning (RIC) regimens for these patients. Here we report our 8-year single-center experience. Sixteen consecutive patients diagnosed with XLP1 underwent allogeneic HCT between 2006 and 2013 after a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan. Patient phenotypes included hemophagocytic lymphohistiocytosis (HLH) after Epstein-Barr virus (n = 5) or human herpesvirus 6 (n = 1), macrophage activation syndrome (n = 1), interstitial pneumonitis and encephalitis (n = 1), B cell lymphoma (n = 8), and hypogammaglobulinemia (n = 2). One patient was asymptomatic. Fourteen of 16 patients received 8/8 HLA-matched unrelated or related bone marrow grafts, whereas 2 patients received mismatched unrelated grafts. Acute graft-versus-host disease (GVHD) prophylaxis consisted of methylprednisolone and cyclosporine in all but 1 patient, who additionally received methotrexate. All patients had hematopoietic recovery. There were no cases of hepatic veno-occlusive disease or pulmonary hemorrhage. One patient (6%) developed acute GVHD and later also developed chronic GVHD (6%). Five patients (31%) developed mixed chimerism. Only 1 patient with mixed chimerism (6%) experienced a decline of donor chimerism to less than 50% but returned to full donor chimerism after infusion of donor lymphocytes and a CD34(+) selected stem cell boost. Infectious complications were frequent, particularly viral reactivation. One-year survival estimated by Kaplan-Meier analysis was 80%, with long-term survival estimated at 71%. Survival was similar for patients with or without a history of HLH (86% versus 75%, respectively, P = .70). There were no occurrences of lymphoma or HLH after HCT. RIC HCT with alemtuzumab, fludarabine, and melphalan is an effective treatment for patients with XLP1, offering good survival rates regardless of prior disease manifestations, including HLH. 2014 American Society for Blood and Marrow Transplantation.