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Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations.
Biology of Blood and Marrow Transplantation ( IF 5.609 ) Pub Date : 2019-07-12 , DOI: 10.1016/j.bbmt.2019.07.007
Ibrahim A Ahmed 1 , Midhat S Farooqi 2 , Mark T Vander Lugt 3 , Jessica Boklan 4 , Melissa Rose 5 , Erika D Friehling 6 , Brandon Triplett 7 , Kenneth Lieuw 8 , Blachy Davila Saldana 9 , Christine M Smith 10 , Jason R Schwartz 11 , Rakesh K Goyal 1
Affiliation  

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.

中文翻译:

生殖细胞SAMD9 / SAMD9L突变患者造血细胞移植的结果。

SAMD9和SAMD9L基因中的生殖系突变分别引起MIRAGE(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,并且相关伴有7号染色体缺失,骨髓增生异常综合症(MDS)和骨髓衰竭。在这个回顾性系列中,我们报告了与SAMD9 / SAMD9L突变相关的血液系统疾病患者的异基因造血细胞移植(HCT)结果。12例患者接受了同种异体HCT的MDS治疗(n = 10),先天性巨核细胞血小板减少症(n = 1)和先天性角化不全(n = 1)。外显子组测序显示SAMD9(n = 6)或SAMD9L(n = 6)基因的杂合突变。4名SAMD9患者具有MIRAGE综合征的特征。HCT的中位年龄为2。8年(范围从1.2到12.8年)。调理清髓9例,强度降低3例。MIRAGE综合征病例中存在与综合征相关的合并症(腹泻,感染,肾上腺功能不全,营养不良和电解质紊乱)。一名家族性SAMD9L突变,MDS和病态肥胖的患者未能植入并死于难治性急性髓细胞性白血病。其他11例患者实现了中性粒细胞植入。在MIRAGE病例中,急性移植后病程并发与综合征相关的合并症。患有SAMD9L相关MDS的患者死于弥漫性肺泡出血。其他10例患者血液学疾病得到缓解,持续供血者嵌合。12名患者中有10名还活着,中位随访时间为3.1年(范围为0.1到14.7年)。
更新日期:2019-07-12
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