Management and Treatment of Monosomy 7
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. 1
Risk Stratification Based on Underlying Syndrome
The management approach critically depends on the underlying germline predisposition syndrome:
SAMD9/SAMD9L Syndromes - Special Consideration
In young children (<3 years) with SAMD9/SAMD9L syndromes, close surveillance may be appropriate initially rather than immediate HSCT, as monosomy 7 can be transient with spontaneous hematological remission occurring within 14 months in some cases 2
Spontaneous resolution is accompanied by somatic genetic rescue events that eliminate the variant allele 1
However, approximately 50% of SAMD9/SAMD9L patients with monosomy 7 acquire additional leukemia-driver mutations (SETBP1, ASXL1, RUNX1, RAS pathway genes), indicating progression risk 1
Serial molecular monitoring with myeloid gene panels is mandatory during surveillance to detect acquisition of these high-risk mutations 1
HSCT should be performed immediately if additional driver mutations are detected, disease progresses to MDS with excess blasts, or severe infections occur 2
GATA2 Deficiency
Monosomy 7 in GATA2 deficiency is a high-risk feature strongly associated with malignant transformation, particularly when accompanied by somatic mutations in SETBP1, ASXL1, RUNX1, and RAS pathway genes 1
Proceed directly to allogeneic HSCT as this represents advanced disease with high progression risk 1
Fanconi Anemia (FA)
Monosomy 7 in FA, along with gain of 1q or 3q and somatic RUNX1 mutations, is associated with progression to MDS/AML 1
Allogeneic HSCT is indicated given the poor prognosis and high transformation risk 1
Other Bone Marrow Failure Syndromes
- In Shwachman-Diamond syndrome (SDS), telomere biology disorders (ThD), severe congenital neutropenia (SCN), and ERCC6L2-related syndromes, monosomy 7 indicates high-risk disease requiring HSCT evaluation 1
Chemotherapy Considerations
Intensive chemotherapy alone has historically shown poor outcomes in monosomy 7 cases, with frequent treatment resistance and early relapse (typically within 9 months) 3, 4, 5
In older studies, children with monosomy 7 MPD who received only supportive care and low-dose chemotherapy all died within 4-48 months 3
Even when remission is achieved with intensive chemotherapy, relapse is common and survival without HSCT is poor 3, 4
Chemotherapy may be used as a bridge to transplant in cases with excess blasts, but should not be considered definitive therapy 3
Molecular Monitoring Requirements
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 1
Panels should include genes associated with clonal evolution: SETBP1, ASXL1, RUNX1, RAS pathway genes, TP53, STAG2, DNMT3A 1
Standard cytogenetics should be performed serially to monitor monosomy 7 clone size 1, 2
HLA Typing
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 1
Sibling typing should be performed simultaneously when available 1
Common Pitfalls
Do not delay HSCT in most monosomy 7 cases based on the SAMD9/SAMD9L data - spontaneous resolution is specific to young children with these syndromes and does not apply to other contexts 1, 2
Even in SAMD9/SAMD9L cases, delaying HSCT poses substantial risk of severe infection and disease progression - four of seven patients in one series required HSCT at median 26 months for various complications 2
Monosomy 7 in pediatric patients requires FISH confirmation if standard cytogenetics shows insufficient metaphases 1
The presence of monosomy 7 alone without additional driver mutations in SAMD9/SAMD9L syndromes has unclear prognostic value and requires close monitoring rather than automatic HSCT 1