Shah Nirali N, Freeman Alexandra F, Su Helen, Cole Kristen, Parta Mark, Moutsopoulos Niki M, Baris Safa, Karakoc-Aydiner Elif, Hughes Thomas E, Kong Heidi H, Holland Steve M, Hickstein Dennis D
Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Biol Blood Marrow Transplant. 2017 Jun;23(6):980-990. doi: 10.1016/j.bbmt.2017.03.016. Epub 2017 Mar 10.
Dedicator-of-cytokinesis 8 (DOCK8) deficiency, a primary immunodeficiency disease, can be reversed by allogeneic hematopoietic stem cell transplantation (HSCT); however, there are few reports describing the use of alternative donor sources for HSCT in DOCK8 deficiency. We describe HSCT for patients with DOCK8 deficiency who lack a matched related or unrelated donor using bone marrow from haploidentical related donors and post-transplantation cyclophosphamide (PT/Cy) for graft-versus-host disease (GVHD) prophylaxis. Seven patients with DOCK8 deficiency (median age, 20 years; range, 7 to 25 years) received a haploidentical related donor HSCT. The conditioning regimen included 2 days of low-dose cyclophosphamide, 5 days of fludarabine, 3 days of busulfan, and 200 cGy total body irradiation. GVHD prophylaxis consisted of PT/Cy 50 mg/kg/day on days +3 and +4 and tacrolimus and mycophenolate mofetil starting at day +5. The median times to neutrophil and platelet engraftment were 15 and 19 days, respectively. All patients attained >90% donor engraftment by day +30. Four subjects developed acute GVHD (1 with maximum grade 3). No patient developed chronic GVHD. With a median follow-up time of 20.6 months (range, 9.5 to 31.7 months), 6 of 7 patients are alive and disease free. Haploidentical related donor HSCT with PT/Cy represents an effective therapeutic approach for patients with DOCK8 deficiency who lack a matched related or unrelated donor.
细胞分裂素8（DOCK8）缺陷是一种原发性免疫缺陷病，可通过异基因造血干细胞移植（HSCT）得到逆转；然而，关于在DOCK8缺陷中使用替代供体来源进行HSCT的报道很少。我们描述了对缺乏匹配的相关或无关供体的DOCK8缺陷患者进行HSCT的情况，使用来自单倍体相合相关供体的骨髓，并使用移植后环磷酰胺（PT/Cy）预防移植物抗宿主病（GVHD）。7例DOCK8缺陷患者（中位年龄20岁；范围7至25岁）接受了单倍体相合相关供体HSCT。预处理方案包括2天低剂量环磷酰胺、5天氟达拉滨、3天白消安和200 cGy全身照射。GVHD预防包括在+3和+4天给予PT/Cy 50mg/kg/天，以及从+5天开始给予他克莫司和霉酚酸酯。中性粒细胞和血小板植入的中位时间分别为15天和19天。所有患者在+30天时供体植入率均>90%。4例患者发生急性GVHD（1例最高为3级）。无患者发生慢性GVHD。中位随访时间为20.6个月（范围9.5至31.7个月），7例患者中有6例存活且无疾病。采用PT/Cy的单倍体相合相关供体HSCT是缺乏匹配的相关或无关供体的DOCK8缺陷患者的一种有效治疗方法。
