What are the treatment options for a patient with Monosomy 7 (a chromosomal abnormality) associated with hematological disorders, such as myelodysplastic syndromes or acute myeloid leukemia?

Monosomy 7: Treatment Approach

Allogeneic hematopoietic stem cell transplantation (HSCT) is the definitive treatment for monosomy 7 and should be pursued urgently, as this high-risk cytogenetic abnormality is associated with poor response to chemotherapy alone, high relapse rates, and dismal outcomes without transplantation. 1

Immediate Risk Stratification

Monosomy 7 represents a high-risk cytogenetic abnormality across all myeloid malignancies and requires immediate evaluation for HSCT candidacy 1. The prognosis varies by disease context:

• MDS with monosomy 7 alone: 3-year survival of 56% with appropriate treatment 2
• AML with monosomy 7 alone: 3-year survival of only 13%, significantly worse than AML with other cytogenetic abnormalities (44%) 2
• Median overall survival: 32 months for monosomy 7 versus 50 months for normal chromosome 7 3

Essential Baseline Workup

HLA Typing and Donor Search

Perform high-resolution molecular HLA typing (classes I and II) immediately at diagnosis for all patients aged <55 years who are HSCT candidates 1. Initiate unrelated donor search simultaneously if no matched sibling is available.

Molecular Monitoring

Serial somatic gene panels from bone marrow must be performed at baseline and with each subsequent evaluation, particularly screening for high-risk mutations including SETBP1, ASXL1, RUNX1, and RAS pathway genes 1. Approximately 50% of patients with monosomy 7 acquire additional leukemia-driver mutations indicating progression risk 1.

Cytogenetic Analysis

Analyze ≥20 metaphases to identify additional chromosomal abnormalities 4. Monosomy 7 as the sole abnormality occurs in 75% of MDS cases but only 32% of AML cases 2. Complex karyotypes with monosomy 7 carry particularly poor prognosis 5.

Treatment Algorithm by Disease Context

MDS with Monosomy 7

For refractory anemia (RA) or RAEB without excess blasts:

• Proceed directly to allogeneic HSCT without prior chemotherapy 2
• Patients with RA, RAEB, or JMML treated with BMT without prior chemotherapy achieved 3-year survival of 73% 2
• Stable disease for several years was documented in more than half of patients with RA or RAEB, but ultimate progression is inevitable without transplant 2

For RAEB in transformation (RAEB-T) with 10-19% blasts:

• Consider bridging chemotherapy to reduce blast burden before HSCT 1
• 3-year survival for RAEB-T is only 8%, emphasizing urgency of transplant 2

AML with Monosomy 7

Induction chemotherapy as bridge to transplant:

• Standard "7+3" induction: cytarabine 100-200 mg/m² continuous infusion for 7 days plus daunorubicin 60-90 mg/m² or idarubicin 12 mg/m² on days 1-3 4
• Intensive chemotherapy alone shows poor outcomes with frequent treatment resistance and early relapse 1
• All AML patients with monosomy 7 who achieved remission with chemotherapy relapsed within 9 months without transplant 6

Proceed to myeloablative allogeneic HSCT in first complete remission:

• Do not delay for consolidation chemotherapy cycles 4
• Monosomy 7 defines high-risk AML requiring transplant in CR1 4

Germline Predisposition Syndromes

GATA2 deficiency, Fanconi Anemia, or SAMD9/SAMD9L mutations:

• Proceed directly to allogeneic HSCT when monosomy 7 is detected 1
• These patients have particularly high risk of malignant transformation 1
• Predisposing conditions were found in 20% of pediatric monosomy 7 cases 2

Critical Pitfalls to Avoid

Do not pursue chemotherapy alone as definitive therapy: Historical data demonstrates dismal outcomes with chemotherapy-only approaches, with 3-year survival of 13% in AML and inevitable progression in MDS 2. Children with chronic myeloproliferative disease who received supportive care and low-dose chemotherapy alone all died, surviving between 4 months and 4 years 6.

Do not delay transplant for multiple consolidation cycles: Early BMT offers the best chance of survival 6. One child with myeloproliferative disease who underwent successful BMT survived 7.5 years after presentation, while those treated with chemotherapy alone died within 4 years 6.

Distinguish monosomy 7 from del(7q): While both are adverse, complete monosomy 7 carries worse prognosis than del(7q), with lower complete remission rates (47.6% vs 70%) and higher death rates (62% vs 40%) 3. Median overall survival is 32 months for monosomy 7 versus 43 months for del(7q) 3.

Monitor for clonal evolution in Ph-negative cells: In CML patients treated with tyrosine kinase inhibitors, monosomy 7 or del(7q) in Ph-negative cells indicates risk of myelodysplasia and acute leukemia, justifying long-term follow-up bone marrow biopsies 7.

Morphologic Features Suggesting Monosomy 7

Dyserythropoiesis was present in 100% of MDS cases and 38% of AML cases with chromosome 7 abnormalities 5. Dysmyelopoiesis occurred in 66% of MDS and 40% of AML cases 5. Eosinophilia was seen in 56% of MDS and 21% of AML cases with monosomy 7 5. These morphologic features should prompt cytogenetic analysis even when blast percentage is low 5.