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

Introduction: 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.
Methods: A comprehensive analysis was conducted on 309 consecutive patients diagnosed with either multiple myeloma or pPCL, utilizing peripheral blood smears stained with Wright–Giemsa.
Results: 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 >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 < 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.
Conclusion: 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, but Myc rearrangements and CPC positivity could serve as ultra-high-risk factors for multiple myeloma.

引言：原发性浆细胞白血病（primary plasma cell leukemia, pPCL）的定义已从循环浆细胞（circulating plasma cells, CPC）占比≥20%修订为≥5%，但循环浆细胞相关的精准预后仍存在争议。本研究旨在基于循环浆细胞的存在情况，探究多发性骨髓瘤患者的预后生物标志物。
方法：本研究对309例连续纳入的确诊为多发性骨髓瘤或原发性浆细胞白血病的患者开展综合分析，采用瑞氏-吉姆萨（Wright–Giemsa）染色的外周血涂片进行检测。
结果：研究按循环浆细胞百分比将患者分为四组：0%组（221例，占比71.5%）、1%~4%组（49例，占比15.9%）、5%~19%组（16例，占比5.2%）以及≥20%组（23例，占比7.4%）。循环浆细胞占比＞5%的患者多伴随贫血、肾功能不全及国际分期系统（International Staging System, ISS）分期偏晚期等不良临床特征。循环浆细胞阳性患者中常见的细胞遗传学异常包括1q21扩增、17p缺失及Myc基因重排。循环浆细胞≥5%患者的中位无进展生存期（progression-free survival, PFS）与总生存期（overall survival, OS）均更短，其中位无进展生存期为10.03个月，显著短于其余患者的29.47个月；中位总生存期为12.30个月，同样显著短于其余患者的64.10个月。此外，未接受自体造血干细胞移植（autologous hematopoietic stem cell transplantation, ASCT）的循环浆细胞阳性患者，以及一线治疗方案疗效未达部分缓解（partial remission, PR）的患者，其无进展生存期与总生存期均更短。本研究还发现，软组织相关髓外疾病与更差的无进展生存期相关，而Myc基因重排则与更短的总生存期相关。
结论：循环浆细胞阳性患者的生物学特征更具侵袭性，其无进展生存期与总生存期均显著缩短。循环浆细胞阳性状态、自体造血干细胞移植及总体缓解率均为独立预后因素。本研究未提出基于循环浆细胞的原发性浆细胞白血病新诊断阈值，但Myc基因重排与循环浆细胞阳性可作为多发性骨髓瘤的超高危危险因素。