Which cytogenetic abnormality in multiple myeloma is associated with the most favorable prognosis?

Explanation

## Cytogenetic Abnormalities and Prognosis in Multiple Myeloma **Key Point:** t(11;14) involving CCND1 (cyclin D1) and IGH is considered a standard-risk or favorable-risk cytogenetic abnormality, associated with the most favorable prognosis among recurrent translocations in myeloma. ### Cytogenetic Risk Stratification | Abnormality | Mechanism | Prognosis | Frequency | |-------------|-----------|-----------|----------| | **t(11;14)(CCND1;IGH)** | Cyclin D1 overexpression | **Favorable/Standard risk** | 15–20% | | **t(6;14)(CCND3;IGH)** | Cyclin D3 overexpression | Favorable/Standard risk | 5% | | t(4;14)(FGFR3;IGH) | FGFR3/MMSET activation | High risk | 15–20% | | Deletion 13q | Loss of RB1 pathway | High risk (if sole abnormality) | 50% | | Deletion 17p (TP53) | Loss of p53 tumor suppressor | **Very high risk** | 10% | | Gain 1q | Increased gene dosage | High risk | 30% | **High-Yield:** The International Myeloma Working Group (IMWG) classifies cytogenetics into three risk categories: - **Standard risk:** t(3;14), t(11;14), t(6;14), hyperdiploidy, non-hyperdiploid without high-risk features - **High risk:** t(4;14), t(14;16), deletion 17p - **Very high risk:** Deletion 17p (especially biallelic), t(4;14) + deletion 17p **Clinical Pearl:** Patients with t(11;14) myeloma often have indolent disease and may not require immediate treatment (smoldering myeloma). Conversely, deletion 17p is the single most adverse prognostic factor and mandates aggressive therapy. **Mnemonic:** **CCND1 = Calm** — t(11;14) is the calmest, most indolent translocation; **17p = Severe** — deletion 17p is the most severe.