Scudla V, Bacovský J, Indrák K, Kod'ousková V, Vytrasová M, Faber E, Papajík T, Vavrdová V, Adam Z, Hájek R, Farbiaková V, Srovnalík K, Novosadová L, Vránová M, Micaníková M, Sumná E, Kuca B, Slezar J, Heincová V, Gumulec J, Zivná J, Schlemmer P, Lautnerová E, Lasota Z, Kubecková M, Krajsová I, Růzicka M, Cíhal K, Martínek A, Cernosek B, Doubravský J, Papajík J, Prodĕlal P
III. interní klinika Lékarské fakulty UP a FN, Olomouc.
Vnitr Lek. 2002 Aug;48(8):707-17.
The objective of the investigation is evaluation of therapeutic results and the development of the prognosis of patients with multiple myeloma (MM) as a result of consecutive changes of therapeutic procedures in patients of central and northern Moravia in the course of the last 40 years.
The analyzed group of 562 patients with MM was concentrated at the Ist and IIIrd Medical Clinic of the Faculty Hospital Olomouc in 1959 - 2000, median age 63 (28-91) male/female ratio 1.1: 1.0. From analysis of Kaplan-Meier survival curves and the results of statistical analysis (log rank test p = 0.0000) ensued that during the evaulated period a very substantial change of prognosis occurred with improvement of theraupeutic results and a significant prolongation of survival in general. The first " turning point" was the introduction of chemotheraphy with alkylating substances with Prednisone (1963-1975), leading as compared with the period of symptomatic treatment alone (1959-1063) to a significant prolongation of the media value of general survival (M) from 8 to 19 months (p = 0.0031) and 3-year survival from 4 to 23 % patients, whereby 10-year survival was only 0 % and 1 %. The second "turning point" was the period from 1976 - 1980 with introduction of systematic chemotherapy using conventional doses of polychemotherapeutic (CP) regimes with better opportunities of supporting treatment (M = 40 months, p = 0.0000; 3-year and 10-year survival 55% and 5.5% patients). The therapeutic results acheived during the subsequent 15 years were however an unsatisfactory advance. During the interval between 1976-1995 in a group of 295 patients divided into 5-year sub-periods remission was acheived (R = < 25 % of the baseline value of M-protein) in 10-24 % patients, an inadequate response (NR) = persistence in > 50 % M-protein) in 55-28 %, prolongation of the median of total survival in 232 of the accessble patients for 44 months and long-term survival of 5 - 10 years after establisment of the diagnosis increased from 25 to 36 % and from 5.5 to 16.5 % patients. The third "turning point" was 1996 characterized by the introduction of high-dosage chemotheraphy with transplantation of autologuos peripheral haematopoietic cells ("HD" therapy with ASCT) leading ina group of so far only 33, assessable patients under 65 years to acheived remission in 71 %, to decline of NR in 10 % only and 5 -year suvival so far in 91 % patients ( p = 0.0037). Improvement of therapeutic results and prognosis of the disease as compared with 1976 - 1995 occurred in the whole group of patients also in 1996 - 2000 (CP and "HD"-therapy with ASCT) characterized by remission in 36 %, NR IN 33 % and 5 -year survival in 57 % (p = 0.030). It was reveled that the application of "HD" theraphy with ASCT led in 1995-2000 to the acheivement of more favorable therapeutic results (R - 71 % NR - 10 %. 5-year survival after the interval which elapsed so far 91 %), as compared with 2 similar groups of subjects under 65 years meeting the criteria of "HD" theraphy with ASCT, but treated only by conventional polychemotheraphy (1991 - 1995 and 1996 - 2000: R - 24 and 32 %, NR - 42 and 23 %, 5-year survival 46 and 68 % of the patients). In the group of 148 patients from the period of 1991-2000 the patients had as regards remission (R) more favourable results as compared with patients with NR concerning the prognosis [M 63 vs.22 months, 5-year and 10-year survival 53 vs. 17 % and 17 vs. 0 % of patients (p = 0.0000)].
From the submitted analysis ensured that during the period form 1959 - 2000 in patients with mutiple myeloma in central and northern Moravia as a result of the application of modern methods of chemotheraphy and supporting treatment a significant improvements of results of conventional treatment occurred with a more than 5 fold prolongation of so far assessable median values of survival (8 - 44 months) and long-term 10-year survival of almost one sixth of the patients. The real asset of "HD" theraphy with transplantation of ASCT will be revealed by analyses made after a longer time interval.
本研究旨在评估过去40年中摩拉维亚中部和北部地区患者因治疗方案的连续变化而导致的多发性骨髓瘤（MM）患者的治疗效果及预后发展情况。
分析的562例MM患者集中于1959 - 2000年奥洛穆茨大学医院第一和第三内科诊所，中位年龄63岁（28 - 91岁），男女比例为1.1:1.0。通过对Kaplan-Meier生存曲线的分析和统计分析结果（对数秩检验p = 0.0000）可知，在评估期内，随着治疗效果的改善和总体生存期的显著延长，预后发生了非常显著的变化。第一个“转折点”是引入烷化剂与泼尼松联合化疗（1963 - 1975年），与仅进行对症治疗的时期（1959 - 1963年）相比，总体生存期的中位值（M）从8个月显著延长至19个月（p = 0.0031），3年生存率从4%提高到23%的患者，而10年生存率仅为0%和1%。第二个“转折点”是1976 - 1980年期间，引入使用常规剂量多药化疗（CP）方案的系统化疗，并有更好的支持治疗机会（M = 40个月，p = 0.0000；3年和10年生存率分别为55%和5.5%的患者）。然而，在随后的15年中取得的治疗效果进展并不理想。在1976 - 1995年期间，将295例患者分为5年亚组，10 - 24%的患者实现缓解（R = M蛋白基线值的< 25%），55 - 28%的患者反应不足（NR = M蛋白持续> 50%），在可评估的232例患者中，总生存期的中位数延长至44个月，诊断确立后5 - 10年的长期生存率从25%提高到36%，从5.5%提高到16.5%的患者。第三个“转折点”是1996年，其特点是引入高剂量化疗并进行自体外周造血细胞移植（“HD”疗法联合ASCT），在一组截至目前仅33例、年龄在65岁以下的可评估患者中，71%实现缓解，仅10%的患者NR下降，目前91%的患者5年生存率（p = 0.0037）。与1976 - 1995年相比，1996 - 2000年整个患者组的治疗效果和疾病预后也有所改善（CP和“HD”疗法联合ASCT），缓解率为36%，NR为33%，5年生存率为57%（p = 0.030）。结果显示，与2组符合“HD”疗法联合ASCT标准但仅接受传统多药化疗的65岁以下类似受试者组（1991 - 1995年和1996 - 2000年：缓解率分别为24%和32%，NR分别为42%和23%，5年生存率分别为46%和68%的患者）相比，1995 - 2000年应用“HD”疗法联合ASCT取得了更有利的治疗效果（缓解率 - 71%，NR - 10%，到目前为止经过的间隔期后的5年生存率91%）。在1991 - 2000年的148例患者组中，与NR患者相比，缓解（R）患者在预后方面取得了更有利的结果[M分别为63个月和22个月，5年和10年生存率分别为53%和17%以及17%和0%的患者（p = 0.0000）]。
从提交的分析可知，在1959 - 2000年期间，由于应用现代化疗方法和支持治疗，摩拉维亚中部和北部地区的多发性骨髓瘤患者的传统治疗效果有了显著改善，可评估的生存中位数延长了5倍多（从8个月延长至44个月），近六分之一的患者实现了10年长期生存。“HD”疗法联合ASCT的真正优势将在更长时间间隔后的分析中显现出来。
