Cuellar-Rodriguez Jennifer, Freeman Alexandra F, Grossman Jennifer, Su Helen, Parta Mark, Murdock Heardley, Shah Nirali, Bollard Catherine, Kong Heidi H, Moutsopoulos Niki, Stone Kelly, Gea-Banacloche Juan, Holland Steven M, Hickstein Dennis D
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Division of Hematology and Hematologic Malignancies, Alberta Health Services, Calgary, Alberta, Canada.
Biol Blood Marrow Transplant. 2015 Jun;21(6):1037-45. doi: 10.1016/j.bbmt.2015.01.022. Epub 2015 Jan 27.
We performed allogeneic hematopoietic stem cell transplantation in 6 patients with mutations in the dedicator-of-cytokinesis-8 (DOCK8) gene using a myeloablative conditioning regimen consisting of busulfan 3.2 mg/kg/day i.v. for 4 days and fludarabine 40 mg/m(2)/day for 4 days. Three patients received allografts from matched related donors and 3 patients from matched unrelated donors. Two patients received peripheral blood stem cells and 4 patients bone marrow hematopoietic stem cells. Tacrolimus and short-course methotrexate on days 1, 3, 6, and 11 were used for graft-versus-host-disease (GVHD) prophylaxis. All 6 patients are alive at a median follow-up of 22.5 months (range, 14 to 35). All patients achieved rapid and high levels of donor engraftment and complete reversal of the clinical and immunologic phenotype. Adverse events consisted of acute skin GVHD in 2 patients and post-transplant pulmonary infiltrates in a patient with extensive bronchiectasis pretransplant. Thus, a uniform myeloablative conditioning regimen followed by allogeneic hematopoietic stem cell transplantation in DOCK8 deficiency results in reconstitution of immunologic function and reversal of the clinical phenotype with a low incidence of regimen-related toxicity.
我们对6例细胞分裂素特异性鸟嘌呤核苷酸交换因子8（DOCK8）基因发生突变的患者进行了异基因造血干细胞移植，采用的清髓预处理方案为：白消安3.2 mg/kg/天，静脉注射，共4天；氟达拉滨40 mg/m²/天，共4天。3例患者接受了来自匹配的相关供者的移植物，3例患者接受了来自匹配的无关供者的移植物。2例患者接受了外周血干细胞，4例患者接受了骨髓造血干细胞。在第1、3、6和11天使用他克莫司和短疗程甲氨蝶呤预防移植物抗宿主病（GVHD）。6例患者均存活，中位随访时间为22.5个月（范围14至35个月）。所有患者均实现了快速且高水平的供者植入，临床和免疫表型完全逆转。不良事件包括2例患者发生急性皮肤GVHD，1例移植前有广泛支气管扩张的患者出现移植后肺部浸润。因此，在DOCK8缺陷患者中，采用统一的清髓预处理方案后进行异基因造血干细胞移植可重建免疫功能，逆转临床表型，且方案相关毒性发生率较低。
