Background:High-risk chromosomal abnormalities (HRCAs) detected by fluorescence in situ hybridization (FISH) have a well-established adverse prognostic impact in multiple myeloma (MM). It is increasingly recognized that the coexistence of two or more HRCAs identifies a particularly poor-risk subgroup, often referred to as double- or multiple-hit MM. However, there is currently no consensus on its definition.Methods:We retrospectively analyzed a multicenter cohort of 1122 newly diagnosed MM patients from 2008 to 2019. Double-hit MM was defined as the coexistence of at least two of the following four HRCAs: t(14;16), gain(1q), del(17p), and del(1p). Based on this definition, we constructed a novel prognostic model, the HBDH (Institute of Hematology & Blood Diseases Hospital) double-hit model, and assessed its prognostic value for progression-free survival (PFS) and overall survival (OS).Results:According to the HBDH model, double-hit patients showed significantly inferior outcomes compared to non-double-hit patients, with median PFS of 20.6 vs. 53.3 months (p< 0.001) and median OS of 40.2 vs. 84.2 months (p< 0.001). The addition of del(13q), t(4;14), or t(11;14) did not improve the prognostic performance of the model. Importantly, the HBDH model was independent of the International Staging System (ISS), elevated LDH, and advanced age.Conclusions: The HBDH double-hit model identifies a subset of ultra-high-risk MM patients carrying at least two major HRCAs, providing a simple and robust framework for prognostic stratification and a potential reference for future biologically driven treatment approaches.
背景：荧光原位杂交（FISH）检测到的高危染色体异常（HRCA）在多发性骨髓瘤（MM）中具有明确的不良预后影响。越来越多的研究认识到，两种或以上HRCA共存可界定一个预后极差的亚组，通常称为双打击或多打击MM，但目前对其定义尚未达成共识。 方法：我们回顾性分析了2008年至2019年1122例新诊断MM患者的多中心队列。双打击MM定义为以下四种HRCA中至少两种共存：t(14;16)、gain(1q)、del(17p)和del(1p)。基于此定义，我们构建了一个新的预后模型——HBDH（血液病医院）双打击模型，并评估其对无进展生存期（PFS）和总生存期（OS）的预后价值。 结果：根据HBDH模型，双打击患者较非双打击患者预后显著更差，中位PFS分别为20.6个月 vs. 53.3个月（p<0.001），中位OS分别为40.2个月 vs. 84.2个月（p<0.001）。加入del(13q)、t(4;14)或t(11;14)并未提升模型的预后效能。重要的是，HBDH模型独立于国际分期系统（ISS）、LDH升高及高龄等因素。 结论：HBDH双打击模型能识别出携带至少两种主要HRCA的超高危MM患者亚群，为预后分层提供了简洁而可靠的框架，并为未来基于生物学的治疗策略提供了潜在参考依据。
Development of a Cytogenetic Double-Hit Model for Survival Prediction in Multiple Myeloma
肿瘤(癌症)患者之家