Management of Monosomy 7 in Hematopoietic Disorders

Risk Stratification and Treatment Approach

Monosomy 7 requires immediate evaluation for hematopoietic stem cell transplantation (HSCT) in most cases, as it represents a high-risk cytogenetic abnormality associated with progression to MDS/AML and poor response to chemotherapy alone, according to the American Society of Hematology 1, 2
In patients with GATA2 deficiency, monosomy 7 is a high-risk feature strongly associated with malignant transformation, particularly when accompanied by somatic mutations in SETBP1, ASXL1, RUNX1, and RAS pathway genes, and proceeding directly to allogeneic HSCT is recommended by the National Comprehensive Cancer Network 1, 2, 4
In Fanconi Anemia (FA), monosomy 7, along with gain of 1q or 3q and somatic RUNX1 mutations, is associated with progression to MDS/AML, and allogeneic HSCT is indicated by the European Society for Medical Oncology 1, 2, 4, 5
Approximately 50% of SAMD9/SAMD9L patients with monosomy 7 acquire additional leukemia-driver mutations (SETBP1, ASXL1, RUNX1, RAS pathway genes), indicating progression risk, as reported by the American College of Medical Genetics and Genomics 2, 4, 5

Serial somatic gene panels must be performed from bone marrow specimens at baseline and with each subsequent evaluation for syndromes including FA, ThD, GATA2 deficiency, SDS, SCN, and germline SAMD9/SAMD9L, ERCC6L2, and RUNX1 pathogenic variants, as recommended by the College of American Pathologists 1, 4, 6
HLA typing (high-resolution molecular typing of classes I and II) should be performed at diagnosis for patients aged <55 years who are candidates for allogeneic HSCT, according to the European Society for Blood and Marrow Transplantation 7

Intensive chemotherapy alone has historically shown poor outcomes in monosomy 7 cases, with frequent treatment resistance and early relapse, and chemotherapy may be used as a bridge to transplant in cases with excess blasts, but should not be considered definitive therapy, as stated by the American Society of Clinical Oncology 1, 2, 4