Prognostic Implications of Circulating Plasma Cell Percentage in Multiple Myeloma and Primary Plasma Cell Leukemia Defined by New Criteria

Abstract

<b><i>Introduction:</i></b> The definition of primary plasma cell leukemia (pPCL) has been revised from ≥20% to ≥5% circulating plasma cells (CPC). However, the precise prognosis associated with CPC remains controversial. This study aimed to investigate prognostic biomarkers for myeloma patients based on CPC presence. <b><i>Methods:</i></b> A comprehensive analysis was conducted on 309 consecutive patients diagnosed with either multiple myeloma or pPCL, utilizing peripheral blood smears stained with Wright-Giemsa. <b><i>Results:</i></b> Patients were grouped by CPC percentage: 0% (221, 71.5%), 1–4% (49, 15.9%), 5–19% (16, 5.2%), ≥20% (23, 7.4%). CPC &gt;5% correlated with unfavorable characteristics, including anemia, renal dysfunction, and advanced International Staging System. Common cytogenetic abnormalities such as 1q21 amplification, 17p deletion, and Myc rearrangement were prevalent among CPC-positive patients. Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with CPC ≥5% (29.47 vs. 10.03 months; 64.10 vs. 12.30 months). Additionally, PFS and OS were shorter in CPC-positive patients without autologous hematopoietic stem cell transplantation (ASCT) and those with response &lt; partial remission to the first-line regimen. Furthermore, an association emerged between soft tissue-related extramedullary disease and inferior PFS, while Myc rearrangement correlated with abbreviated OS. <b><i>Conclusion:</i></b> Biological characteristics displayed greater aggressiveness in patients with positive CPC, leading to significantly shorter PFS and OS. The presence of CPC, ASCT, and overall response rate were independent prognostic factors. While no new threshold for pPCL with CPCs is proposed, Myc rearrangements and CPC positivity could serve as ultra-high-risk factors for multiple myeloma.