Hose Dirk, Seckinger Anja, Jauch Anna, Rème Thierry, Moreaux Jérôme, Bertsch Uta, Neben Kai, Klein Bernard, Goldschmidt Hartmut
Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany.
Srp Arh Celok Lek. 2011 Dec;139 Suppl 2:84-9. doi: 10.2298/sarh11s2084h.
Multiple myeloma patients' survival under treatment varies from a few months to more than 15 years. Clinical prognostic factors, especially beta2-microglobulin (B2M) and the international staging system (ISS), allow risk assessment to a certain extent, but do not identify patients at very high risk. As malignant plasma cells are characterized by a variety of chromosomal aberrations and changes in gene expression, a molecular characterization ofCD138-purified myeloma cells by interphase fluorescence in situ hybridization (iFISH) and gene expression profiling (GEP) can be used for improved risk assessment, iFISH allows a risk stratification with presence of a translocation t(4;14) and/or deletion of 17p13 being the best documented adverse prognostic factors. A deletion of 13q14 is no longer considered to define adverse risk. Patients harbouring a t(4;14) seems to benefit from a bortezomib- or lenalidomide containing regimen, whereas patients with deletion 17p13 seem only to benefit from a high dose therapy approach using long term bortezomib (in induction and maintenance) and autologous tandem-transplantation as used in the GMMG-HD4 trial, or the total therapy 3 concept. Gene expression profiling allows the assessment of high risk scores (IFM, UAMS), remaining prognostic despite treatment with novel agents, and prognostic surrogates of biological factors (e.g. proliferation) and (prognostic) target gene expression (e.g. Aurora-kinase A). Thus, assessment of B2M and ISS-stage, iFISH, and GEP is considered extended routine diagnostics in therapy requiring multiple myeloma patients for risk assessment and, even now, to a certain extent selection of treatment.
多发性骨髓瘤患者在治疗期间的生存期从几个月到超过15年不等。临床预后因素，尤其是β2-微球蛋白（B2M）和国际分期系统（ISS），在一定程度上能够进行风险评估，但无法识别极高风险的患者。由于恶性浆细胞具有多种染色体畸变和基因表达变化的特征，通过间期荧光原位杂交（iFISH）和基因表达谱分析（GEP）对CD138纯化的骨髓瘤细胞进行分子特征分析可用于改进风险评估。iFISH可根据是否存在t(4;14)易位和/或17p13缺失进行风险分层，这是记录最充分的不良预后因素。13q14缺失不再被视为定义不良风险。携带t(4;14)的患者似乎从含硼替佐米或来那度胺的方案中获益，而17p13缺失的患者似乎仅从使用长期硼替佐米（诱导和维持治疗）和自体串联移植的高剂量治疗方法中获益，如GMMG-HD4试验或总治疗3方案中所采用的。基因表达谱分析可评估高风险评分（IFM、UAMS），即使在使用新型药物治疗后仍具有预后价值，还可评估生物因素（如增殖）和（预后）靶基因表达（如极光激酶A）的预后替代指标。因此，对B2M和ISS分期、iFISH以及GEP的评估被认为是治疗多发性骨髓瘤患者进行风险评估的扩展常规诊断方法，甚至在一定程度上可用于治疗选择。
