What is the best approach to treating a pediatric or young adult patient with 52% monosomy?

Treatment of 52% Monosomy 7

Proceed immediately to allogeneic hematopoietic stem cell transplantation (HSCT) evaluation, as monosomy 7 is classified as an adverse-risk cytogenetic abnormality requiring transplantation as the only potentially curative therapy. 1, 2

Risk Stratification and Prognostic Significance

• Monosomy 7 is definitively classified in the adverse-risk category by both the 2017 European LeukemiaNet (ELN) guidelines for AML and the International Prognostic Scoring System (IPSS), making it one of the most critical prognostic factors determining treatment strategy. 3, 1

• The presence of monosomy 7 provides presumptive evidence of myelodysplastic syndrome (MDS) even without definitive morphologic features, with high-level evidence supporting this classification. 1

• In pediatric populations, monosomy 7 represents an adverse prognostic factor associated with significantly worse event-free survival (P<0.0001) and overall survival (P=0.0007) compared to patients without this abnormality. 3, 4

Immediate Diagnostic Workup

• Confirm the cytogenetic abnormality through conventional G-banding analysis of bone marrow aspirate with at least 20 metaphases analyzed, as this remains the gold standard for detecting monosomy 7. 1

• Perform FISH analysis for monosomy 7 if conventional cytogenetics fails or rapid results are needed, with sensitivity of 80-90%. 3, 1

• Obtain serial somatic gene panels from bone marrow specimens to identify additional leukemia-driver mutations (SETBP1, ASXL1, RUNX1, RAS pathway genes), as approximately 50% of patients with monosomy 7 acquire these mutations indicating progression risk. 2

• Complete high-resolution molecular HLA typing (classes I and II) immediately at diagnosis for transplant planning, particularly for patients under 55 years who are HSCT candidates. 1, 2

Treatment Algorithm

Primary Treatment Approach

• Allogeneic HSCT is the only potentially curative therapy for monosomy 7, with level 1A evidence supporting this recommendation from the American Society of Hematology. 1, 2

• Intensive chemotherapy alone has historically shown poor outcomes with frequent treatment resistance and early relapse, and should not be considered definitive therapy (level 1B evidence). 1, 2

Bridge to Transplant Strategy

• Chemotherapy may be used as a bridge to transplant in cases with excess blasts, but this is strictly a temporizing measure and not curative intent therapy. 2

• For pediatric patients with AML and monosomy 7, induction therapy with combination cytarabine and anthracyclines (daunorubicin) can be used while preparing for HSCT. 5

Special Population Considerations

Germline Predisposition Syndromes

• In patients with GATA2 deficiency, proceed directly to allogeneic HSCT when monosomy 7 is detected, as this represents a high-risk feature strongly associated with malignant transformation. 2

• In Fanconi Anemia patients, monosomy 7 indicates progression to MDS/AML and mandates immediate HSCT evaluation per European Society for Medical Oncology guidelines. 2

Pediatric Patients

• Monosomy 7 is a critical marker of malignant transformation in children, requiring FISH detection due to the prognostic value of this aberration (level 2B evidence). 1

• The critical region of loss in pediatric ALL appears to be on the p-arm of chromosome 7, though this distinction is less relevant for treatment decisions than the overall adverse prognosis. 4

Monitoring Protocol

• Perform serial somatic gene panels from bone marrow specimens at baseline and with each subsequent evaluation for patients with germline predisposition syndromes including Fanconi Anemia, GATA2 deficiency, and severe congenital neutropenia. 1, 2

• Monitor for acquisition of additional mutations (SETBP1, ASXL1, RUNX1, RAS pathway genes) that indicate disease progression and increased urgency for transplantation. 2

Critical Pitfalls to Avoid

• Do not rely on chemotherapy alone as definitive treatment, even if initial response appears favorable, as relapse rates are unacceptably high without HSCT. 1, 2

• Do not delay HLA typing and donor search while pursuing chemotherapy, as time to transplant directly impacts outcomes in adverse-risk cytogenetics. 1, 2

• Do not overlook germline predisposition syndromes that may have monosomy 7 as a manifestation, as these require specific transplant considerations and family counseling. 2