A 66-year-old woman with newly diagnosed multiple myeloma has t(4;14) chromosomal translocation, del(17p), and plasma cell percentage of 60% on bone marrow biopsy. She is not a transplant candidate. According to the R-ISS (Revised International Staging System) staging for myeloma, which combination of factors places her in Stage III (worst prognosis)?
- A β2-microglobulin ≥5.5 mg/L AND high-risk cytogenetics [del(17p), t(4;14), t(14;16)] AND high LDH ✓
- B Serum creatinine >2 mg/dL AND anemia (Hb <8.5 g/dL) AND bone lesions
- C Serum albumin <3.5 g/dL AND β2-microglobulin >3.5 mg/L
- D Plasma cell >60% AND free light chain ratio >100
Correct answer: A. β2-microglobulin ≥5.5 mg/L AND high-risk cytogenetics [del(17p), t(4;14), t(14;16)] AND high LDH
Explanation
The R-ISS (Revised International Staging System, 2015) for multiple myeloma incorporates ISS stage, cytogenetic risk, and serum LDH. R-ISS Stage III = ISS Stage III (β2M ≥5.5 mg/L) PLUS either high-risk cytogenetics [del(17p), t(4;14), or t(14;16)] OR elevated LDH (>upper limit of normal). This patient with del(17p) and t(4;14) has high-risk cytogenetics. Options B and C describe Durie-Salmon and ISS criteria respectively. Option D refers to CRAB criteria/smoldering myeloma thresholds. R-ISS Stage III has a 5-year OS of ~40% versus ~82% for Stage I.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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