Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations
Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations
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DOI：
10.1016/j.bbmt.2019.07.007
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发表时间：
2019-11-01
影响因子：
4.3
通讯作者：
Goyal, Rakesh K.
中科院分区：
文献类型：
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作者：
Ahmed, Ibrahim A.;Farooqi, Midhat S.;Goyal, Rakesh K.
SAMD 9和SAMD 9 L基因中的种系突变分别导致MILITARY（骨髓增生异常、感染、生长受限、肾上腺发育不全、生殖器表型和肠病）（OMIM：*610456）和共济失调-全血细胞减少症（OMIM：*611170）综合征，并与7号染色体缺失、骨髓增生异常综合征（MDS）和骨髓衰竭相关。在这个回顾性系列中，我们报告了SAMD 9/SAMD 9 L突变相关血液病患者的异基因造血细胞移植（HCT）结局。12例患者接受了MDS（n = 10）、先天性无巨核细胞性血小板减少症（n = 1）和先天性角化不良（n = 1）的同种异体HCT。外显子组测序显示SAMD 9（n = 6）或SAMD 9 L（n = 6）基因中的杂合突变。4例SAMD 9患者具有MILLING综合征的特征。HCT时的中位年龄为2.8岁（范围：1.2 - 12.8岁）。9例患者的预处理为清髓性，3例患者的预处理强度降低。综合征相关的合并症（腹泻、感染、肾上腺功能不全、营养不良和电解质失衡）存在于MINUX综合征病例中。1例有家族性SAMD 9 L突变、MDS和病态肥胖的患者未能移植，死于难治性急性髓性白血病。其他11例患者实现了中性粒细胞植入。急性移植后病程并发综合征相关的合并症在心肌梗死病例。1例SAMD 9 L相关MDS患者死于弥漫性肺泡出血。其他10例患者血液学疾病消退，外周血供者嵌合体持续存在。12例患者中有10例存活，中位随访时间为3.1年（范围：0.1 - 14.7年）。需要更多的数据来完善具有显著合并症的SAMD 9/SAMD 9 L患者的移植方法，并为他们的长期随访制定指南。(C)2019年美国移植和细胞治疗学会。爱思唯尔公司出版
Germline mutations in SAMD9 and SAMD9L genes cause MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) (OMIM: *610456) and ataxia-pancytopenia (OMIM: *611170) syndromes, respectively, and are associated with chromosome 7 deletions, myelodysplastic syndrome (MDS), and bone marrow failure. In this retrospective series, we report outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with hematologic disorders associated with SAMD9/SAMD9L mutations. Twelve patients underwent allogeneic HCT for MDS (n = 10), congenital amegakaryocytic thrombocytopenia (n = 1), and dyskeratosis congenita (n = 1). Exome sequencing revealed heterozygous mutations in SAMD9 (n = 6) or SAMD9L (n = 6) genes. Four SAMD9 patients had features of MIRAGE syndrome. Median age at HCT was 2.8 years (range, 1.2 to 12.8 years). Conditioning was myeloablative in 9 cases and reduced intensity in 3 cases. Syndrome-related comorbidities (diarrhea, infections, adrenal insufficiency, malnutrition, and electrolyte imbalance) were present in MIRAGE syndrome cases. One patient with a familial SAMD9L mutation, MDS, and morbid obesity failed to engraft and died of refractory acute myeloid leukemia. The other 11 patients achieved neutrophil engraftment. Acute post-transplant course was complicated by syndrome-related comorbidities in MIRAGE cases. A patient with SAMD9L-associated MDS died of diffuse alveolar hemorrhage. The other 10 patients had resolution of hematologic disorder and sustained peripheral blood donor chimerism. Ten of 12 patients were alive with a median follow-up of 3.1 years (range, 0.1 to 14.7 years). More data are needed to refine transplant approaches in SAMD9/SAMD9L patients with significant comorbidities and to develop guidelines for their long-term follow-up. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.