DOI: 10.1016/j.bbmt.2019.07.007; PMCID: PMC7110513
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.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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
Germline; Inherited bone marrow failure syndromes; MIRAGE syndrome; Monosomy 7; Myelodysplastic syndrome; SAMD9/SAMD9 mutations
Ahmed, I. A., Farooqi, M. S., Vander Lugt, M. T., Boklan, J., Rose, M., Friehling, E. D., Triplett, B., Lieuw, K., Saldana, B., Smith, C. M., Schwartz, J. R., Goyal, R. K. Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 25, 2186-2196 (2019).