Document Type

Article

Publication Date

11-2019

Identifier

DOI: 10.1016/j.bbmt.2019.07.007; PMCID: PMC7110513

Abstract

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.

Journal Title

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

Volume

25

Issue

11

First Page

2186

Last Page

2196

MeSH Keywords

Allografts; Child, Preschool; Disease-Free Survival; Female; Genetic Diseases, Inborn; Germ-Line Mutation; Hematopoietic Stem Cell Transplantation; Humans; Infant; Intracellular Signaling Peptides and Proteins; Male; Myelodysplastic Syndromes; Retrospective Studies; Survival Rate; Syndrome; Tumor Suppressor Proteins

Keywords

Germline; Inherited bone marrow failure syndromes; MIRAGE syndrome; Monosomy 7; Myelodysplastic syndrome; SAMD9/SAMD9 mutations

Comments

This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.

Publisher's Online Access: https://doi.org/10.1016/j.bbmt.2019.07.007

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