What does a bone‑marrow chromosome analysis showing trisomy 1 and a derivative chromosome 1;18 in two of five metaphases (with the same abnormalities previously) indicate about disease status, and what are the recommended treatment and follow‑up for this likely relapsed myeloid malignancy?

Bone Marrow Chromosome Analysis: Trisomy 1 and der(1;18) – Disease Status and Management

Disease Status Interpretation

This bone marrow analysis showing persistent trisomy 1 and der(1;18) in 2 of 5 metaphases, identical to previous findings, indicates persistent or relapsed myeloid malignancy requiring immediate clinical correlation and aggressive management consideration. 1

Cytogenetic Significance

• Chromosome 1 abnormalities are among the most frequent chromosomal alterations in myeloid malignancies, particularly involving gains/amplifications of 1q21 and deletions of 1p 1
• The presence of the same abnormalities in sequential samples confirms clonal persistence rather than random events, as clonal abnormalities require at least two metaphases with the same structural change 1
• Gains/amplification of 1q21 increase the risk of disease progression, with higher incidence in relapsed compared to newly diagnosed patients 1
• Chromosome 1 abnormalities are most frequent in BCR-ABL-negative myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, but also occur in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) 2

Clinical Context Assessment

The report notes only 2 of 5 cells analyzed showed abnormalities, with 3 normal cells present. However, the detection of the same clone in previous specimens confirms this is not a technical artifact but represents persistent disease 3, 4. The presence of one non-clonal del(13)(q12q22) may represent an emerging clone, cultural artifact, or random event requiring monitoring 3.

Recommended Diagnostic Workup

Immediate Laboratory Studies

• Complete blood count with differential to assess cytopenias, monocyte count, white blood cell count, and presence of circulating blasts or immature cells 5, 6
• Peripheral blood smear review for monocytosis, dysplastic features, and circulating blasts 5
• Bone marrow aspirate and biopsy assessment for cellularity, blast percentage (using 500-cell differential count), and dysplasia in ≥10% of cells in one or more myeloid lineages 6, 1

Molecular and Cytogenetic Studies

• Comprehensive myeloid mutation panel including SF3B1, TET2, ASXL1, SRSF2, TP53, RUNX1, DNMT3A, IDH1/2, and NRAS/KRAS 5, 1
• JAK2 V617F, CALR, and MPL mutation testing to exclude BCR-ABL-negative myeloproliferative neoplasms 5, 6
• FISH analysis for del(5q), monosomy 7/del(7q), del(17p13), trisomy 8, and del(20q) to identify additional high-risk abnormalities 1
• TP53 mutation analysis is particularly critical as it confers poor prognosis and may influence early transplant consideration 5, 1

Flow Cytometry

• Flow cytometry immunophenotyping to detect abnormalities in erythroid, immature myeloid, maturing granulocytes, and monocyte compartments 5, 6

Risk Stratification

Once complete diagnostic workup is obtained:

• Apply IPSS-R scoring system if MDS is diagnosed 5, 1
• Use disease-specific scoring for MPN if myeloproliferative features predominate 5
• Consider CMML-specific prognostic scores if MDS/MPN overlap features are present 5
• Chromosome 1 abnormalities, particularly 1q gains, are associated with higher risk and should influence risk stratification 1, 2

Treatment Recommendations

For Confirmed Relapsed Disease

• Allogeneic stem cell transplantation should be considered early in appropriate candidates, particularly if TP53 mutations or other high-risk features are identified 5
• Complex karyotypes (≥3 independent abnormalities) are associated with poor prognosis and terminal disease phase, warranting aggressive intervention 7, 8

Common Pitfalls to Avoid

• Do not dismiss the finding because only 2 of 5 cells showed abnormalities – the persistence from previous samples confirms clonality 3, 4
• Do not delay molecular testing – comprehensive mutation panels provide both diagnostic clarification and critical prognostic information 5, 1
• Do not ignore the non-clonal del(13)(q12q22) – document this finding for future comparison as it may represent an emerging clone 3
• Ensure adequate metaphase analysis (20-25 metaphases) in follow-up studies to avoid missing smaller clonal populations 1

Follow-Up Strategy

• Serial cytogenetic monitoring every 3-6 months to detect karyotypic evolution, as changes in karyotype are associated with disease progression and transformation 7, 8
• Monitor for development of complex karyotype (≥3 abnormalities), which is strongly associated with leukemic transformation 8, 7
• Assess for clinical deterioration including worsening cytopenias, increasing blast count, or new symptoms 4, 6