What is the expected outcome for a patient with Monosomy 7 (a chromosomal abnormality) if left untreated?

Expected Outcome of Untreated Monosomy 7

Without treatment, monosomy 7 carries a dismal prognosis with median overall survival of 13-32 months depending on disease context, with inevitable progression to acute myeloid leukemia or death from bone marrow failure. 1, 2

Natural History by Disease Context

Myelodysplastic Syndrome (MDS) with Monosomy 7

• Median overall survival ranges from 13-21 months for untreated high-risk and very high-risk patients according to IPSS-R stratification 1
• Median time to AML evolution is 0.8-1.6 years, with very high-risk patients progressing in 0.8 years and high-risk patients in 1.6 years 1
• Patients with monosomy 7 as a sole abnormality have slightly better outcomes (median OS 32 months) compared to those with complex karyotypes (median OS 13 months) 2

Acute Myeloid Leukemia (AML) with Monosomy 7

• Complete monosomy 7 in AML has particularly poor outcomes with median overall survival of approximately 32 months when untreated, though most patients die much sooner from disease complications 2
• AML with monosomy 7 demonstrates frequent treatment resistance and early relapse even when chemotherapy is attempted 3
• Patients with monosomy 7 alone in AML have worse outcomes (3-year survival 13%) compared to other cytogenetic abnormalities (3-year survival 44%) 4

Chronic Myeloproliferative Disease (MPD) in Children

• All children with monosomy 7 MPD who received only supportive care died within 4 months to 4 years, with death occurring from bone marrow failure, evolution to AML, or progression to myelofibrosis 5
• The disease demonstrates particularly aggressive behavior in pediatric populations with inevitable fatal outcomes without transplantation 5

Mechanisms of Disease Progression

Clonal Evolution and Molecular Progression

• Approximately 50% of patients acquire additional leukemia-driver mutations including SETBP1, ASXL1, RUNX1, and RAS pathway genes, which accelerate progression to acute leukemia 6, 3
• The presence of complex karyotypes (≥3 abnormalities) alongside monosomy 7 confers the worst prognosis with median survival of only 13 months 1

Clinical Manifestations Leading to Death

• Bone marrow failure manifesting as severe cytopenias with life-threatening infections, bleeding, and transfusion-dependent anemia 7, 5
• Progression to acute leukemia occurs in the majority of MDS cases, with blast counts rising inexorably 1, 4
• Myelofibrosis can develop in chronic myeloproliferative variants, leading to complete marrow failure 5

Comparative Outcomes: Untreated vs. Treated

Impact of Treatment on Survival

• While untreated high-risk patients have median survival of 21 months, azacitidine treatment extends this to 25 months 1
• Allogeneic HSCT dramatically improves outcomes to 40 months median survival for high-risk patients and 31 months for very high-risk patients, representing a 2-3 fold improvement over no treatment 1
• In pediatric MPD with monosomy 7, intensive chemotherapy and BMT achieved long-term survival in select cases (up to 7.5 years), while all supportive care patients died within 4 years 5

Special Population Considerations

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 6, 3
• These patients demonstrate high rates of acquiring additional somatic mutations that accelerate malignant transformation 3

Age-Related Differences

• Pediatric patients with monosomy 7 demonstrate variable outcomes by morphologic diagnosis: 3-year survival of 82% in refractory anemia, 45% in JMML, 34% in AML, and only 8% in RAEB-T when treated conservatively 4
• The median age at presentation is 2.8 years, with JMML presenting earliest at 1.1 years 4

Clinical Trajectory Without Intervention

The untreated course follows a predictable pattern: initial cytopenias worsen progressively, transfusion requirements escalate, infectious complications become life-threatening, and either bone marrow failure or transformation to acute leukemia proves fatal within 1-3 years for most patients 1, 5, 2. The aggressive biology of monosomy 7, characterized by NAMPT haploinsufficiency and accumulation of additional mutations, makes spontaneous remission essentially impossible 8.