How should a patient with monosomy 7 in myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) be evaluated and managed?

Monosomy 7 in MDS/AML: Evaluation and Management

Monosomy 7 is a high-risk cytogenetic abnormality requiring immediate evaluation for allogeneic hematopoietic stem cell transplantation (HSCT), which is the only potentially curative therapy and should be pursued in all eligible patients. 1, 2, 3

Immediate Diagnostic Workup

Cytogenetic and Molecular Characterization:

• Perform conventional cytogenetic analysis (G-banding) examining at least 20 metaphases to confirm monosomy 7 and identify whether it is isolated or part of a complex karyotype (≥3 abnormalities), as complex karyotypes confer the worst prognosis with median survival of only 13 months 1, 2, 3
• Add FISH analysis for chromosome 7 when conventional karyotyping is inconclusive or rapid results are needed, with sensitivity of 80-90% 2
• Order molecular testing for high-risk somatic mutations (SETBP1, ASXL1, RUNX1, RAS pathway genes), as approximately 50% of monosomy 7 patients acquire these mutations which accelerate progression to acute leukemia 4, 1, 3

Bone Marrow Assessment:

• Perform bone marrow examination with blast enumeration, multilineage dysplasia assessment, and immunophenotyping to refine prognosis and guide treatment 3
• Blast percentage is critical: <5% indicates lower-risk MDS, 5-9% indicates higher-risk disease, and 10-19% indicates progressively worse outcomes 3

Germline Predisposition Screening:

• Evaluate for germline predisposition syndromes, particularly GATA2 deficiency (MonoMAC syndrome, Emberger syndrome), as monosomy 7 with somatic ASXL1 mutations is often present at transformation in these patients 4
• Consider testing for RUNX1, ETV6, FANC genes, DDX41, and other familial syndromes based on clinical phenotype (thrombocytopenia, immunodeficiency, physical findings, family history) 4

Prognostic Stratification

Survival Without Treatment:

• High-risk MDS with monosomy 7: median overall survival 21 months 1, 3
• Very high-risk MDS with monosomy 7: median overall survival 13 months 1, 3
• Median time to AML transformation: 1.6 years for high-risk, 0.8 years for very high-risk 1, 3

Impact of Cytogenetic Complexity:

• Isolated monosomy 7 in MDS has superior survival compared to monosomy 7 with additional cytogenetic abnormalities (3-year survival 56% vs 24%) 5
• In AML, the reverse is true: isolated monosomy 7 has worse outcomes than monosomy 7 with other abnormalities (3-year survival 13% vs 44%) 5

Treatment Algorithm

For Patients Age <55 Years Without Severe Comorbidities:

• Immediately initiate HLA typing of patient and first-degree relatives, with simultaneous unrelated donor search 2, 3
• Proceed directly to myeloablative allogeneic HSCT from a fully HLA-matched sibling donor during first complete remission for patients with high-risk cytogenetics including monosomy 7 1
• HSCT dramatically improves outcomes: median survival 40 months for high-risk patients and 31 months for very high-risk patients, representing a 2-3 fold improvement over no treatment 1

Bridging Therapy While Awaiting Transplant:

• Hypomethylating agents (azacitidine) can extend median survival to 25 months for high-risk patients and 15 months for very high-risk patients 3
• Intensive chemotherapy alone shows poor outcomes with frequent treatment resistance and early relapse, and should not be considered definitive therapy 2

Pediatric Considerations:

• Monosomy 7 is classified as adverse-risk in pediatric AML and must be distinguished from del(7q), which has comparatively better outcomes 1
• Allogeneic HSCT is particularly effective in children: 69% event-free survival at 2 years, especially for AML in complete remission and MDS 6
• Median age at presentation is 2.8 years, lowest in juvenile myelomonocytic leukemia (JMML) at 1.1 year 5

Critical Pitfalls to Avoid

Diagnostic Errors:

• Do not rely solely on FISH or conventional cytogenetics alone—these are complementary technologies that can give discordant results 7
• The presence of monosomy 7 provides presumptive evidence of MDS even in the absence of definitive morphologic dysplasia 2
• Monosomy 7 with del(5q) removes patients from the favorable-risk del(5q) MDS category, reclassifying them as adverse prognosis 1

Treatment Delays:

• Do not delay transplant evaluation—bone marrow failure manifesting as severe cytopenias with life-threatening infections, bleeding, and transfusion-dependent anemia is a common cause of death 1
• Progression to acute leukemia occurs in the majority of MDS cases with blast counts rising inexorably 1
• Patients transplanted with active leukemia have significantly worse outcomes; four of five deaths in one series occurred in this group 6

Special Population Management

Germline Predisposition Syndromes:

• Patients with GATA2 deficiency, Fanconi anemia, or SAMD9/SAMD9L mutations who develop monosomy 7 have particularly aggressive disease with rapid progression to AML if untreated 1
• Serial somatic gene panels from bone marrow specimens at baseline and with each subsequent evaluation are recommended 2
• Allogeneic HSCT is strongly recommended for these patients (level of evidence 1A) 2

Stable Disease Monitoring:

• More than half of patients with refractory anemia (RA) or refractory anemia with excess blasts (RAEB) can have stable disease for several years 5
• Three-year survival is 82% in RA, 63% in RAEB, but only 8% in RAEB in transformation 5
• Patients with RA, RAEB, or JMML treated with BMT without prior chemotherapy had 3-year survival of 73% 5