International prognostic index (IPI)--a critical comparison with five multiple myeloma staging systems in the group of 270 patients treated by conventional chemotherapy.

In the group of 270 patients with multiple myeloma (MM) treated during 1991-2004 by conventional chemotherapy, the prognostic value and practical utility of IPI (International Prognostic Index) was assessed and compared with five other actual staging systems. Prognostic significance was assessed using the curves of overall survival (OS) according to Kaplan-Meier and log rank test (p<0.05). Good practical utility and prognostic significance of Durie-Salmon (D-S) system was confirmed (p<0.001). Good overall prognostic significance was observed in simple staging systems based on the measurement of beta2-microglobulin and albumin serum levels according to Bataille (p<0.001), SWOG (South West Oncology Group, p<0.001) and IPI (p<0.001). Regardless of a short 5-year duration of the study, the scoring system according to San Miguel enclosing apart from other parameters also propidium iodide proliferation index (PC-PI) of myeloma plasmocytes seems to be promising with very different characteristics of curves of overall survival (p<0.001). Very good prognostic value and easy practical utility were examined in Olomouc staging system (OSS) based on the measurement of beta2-microglobulin and thymidinekinase serum levels (p<0.001). With regard to detection of patients of stage 1, i. e. "low risk", not requiring an immediate initiation of conventional chemotherapy ("wait and see" approach), the most suitable was the system according to D-S, SWOG and IPI (median OS 77, 76 and 77 months). To select a cohort of "high risk" patients, i.e. stage 3, with very unfavourable disease prognosis, the most advantageous was the system OSS and San Miguel (median OS was 5 and 6 months) and/or SWOG system selecting patients of stage 4, i.e. "worst prognosis", with median OS 8 months. It was found that IPI did not meet expectations for effective identification of "high risk" patients (median OS of stage 3 was 20 months) nor for the distinction of different prognosis of patients during initial 25 months of MM course at stage 2 vs. 3. The study indicates that under conditions of common clinical practice and conventional chemotherapy, the staging system according to D-S is still useful, while practical application of SWOG and IPI as simpler alternative to the assessment of clinical stage should be verified by further comparative studies. In harmony with the progress in cytogenetics and molecular biology as well as a prospective requirement of individual target therapy, a future suitable stratification system should be based on parameters of internal biological properties of myeloma tissue and microenvironment of bone marrow, allowing in addition a continuous evaluation of the disease course and the effect of therapy.

[Therapeutic results and changes in prognosis in patients with multiple myeloma in central and northern Moravia over the past 40 years]. / Výsledky lécby a zmena prognózy nemocných s mnohocetným myelomem v období predchozích 40 let v oblasti strední a severní Moravy--rozbor souboru 562 nemocných.

OBJECTIVE: 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. METHODS AND RESULTS: 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)]. CONCLUSION: 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.

[Relation of serum levels of the soluble cytoadhesion molecules sVCAM-1 and sICAM-1 to selected factors in the cytokine network in multiple myeloma]. / Vztah hladin solubilních cytoadhezivních molekul sVCAM-1 a sICAM-1 v séru k vybraným pusobkum cytokinové síte u mnohocetného myelomu.

BACKGROUND: Contemporary, not very frequent studies have brought only few and often inconsistent findings about the significance of cytoadhesive molecules (CAM) type "vascular cell adhesion molecule-1" (VCAM-1) and "intercellular cell adhesion molecule-1" (ICAM-1) at multiple myeloma (MM). The aim of the study was to interpret relations among levels of soluble forms of VCAM-1 and ICAM-1 in serum of the peripheral blood (SPB) and in serum of the aspirated bone marrow (SABM) to concentrations of selected elements of the cytokine network (IL-2, sIL-2R, IL-6, sIL-6R, and TNF-alpha) during different phases of MM disease and to recognise whether there are some specific relations of these factor in both tissue fluids. METHODS AND RESULTS: Two groups of patients with MM were analysed: the group of 64 patients examined in different phases of MM disease and group of 39 patients examined when the disease was diagnosed (age median was 63 and 64 years, male to female relation was 1.6 and 1.3 to 1.0). CAM, cytokine and their soluble receptor levels were estimated using ELISA method. Increased levels of sVCAM-1 in APB were found in 87.5 and 87% of patients; in both groups sVCAM-1 medians almost twice exceeded the upper limits of normality (1180 and 1295 ng/ml). Levels in SABM were always higher (1347 and 1546 ng/ml) than that in SPB. Higher values of sICAM-1 in SPB had 35 and 33% of patients; sICAM-1 medians in SPB and in SABM did not exceed in either group the upper limits of normality (691 ng/ml) and they did not differ significantly (519 vs 476 and 518 vs 500 ng/ml). Statistical analysis (Pearson's correlation quotient, p < 0.05) has shown in both groups significant relation among sVCAM-1 in SPB and SABM levels (p-0.0001 and p-0.0012) and sICAM-1 level (p-0.0002 and p-0.0011) in both types of tissues fluids. In the larger group the statistically significant relation of sVCAM-1 in SPK to sIL-2R (0.0001), sIL-6R (0.0001), TNF-alpha (0.0003), and sICAM-1 (0.042) was found as well as to IL-2 (0.034, sIL-6R (0.044), and sICAM-1 (0.007) in SABM. In the group of 39 patients examined when the MM disease was diagnosed, relation of sVCAM-1 in SPB to levels of sIL-6R (0.0002) and TNF-alpha (0.0001), and in SABM only to sIL-2R (0.009). Evaluation of sICAM-1 revealed relation only to levels of sVCAM-1 both in SPK (0.042) and in SABM (0.007) in the larger group of patients. CONCLUSIONS: The described concentration changes of soluble CAM in serum of the peripheral blood and in serum of the aspirated bone marrow as well as identified relations to levels of various elements of the cytokine network indicate that CAM and especially sVCAM-1, together with elements of the cytokine network play a role in the complicated MM pathology. Particular activity of serum soluble forms sVCAM-1 and sICAM-1 in the pathogenesis of myeloma has not been clarified. It shows that analysis of soluble cytoadhesive molecules sVCAM-1 and sICAM-1 and selected elements of the cytokine network (IL-2, sIL-2R, IL-6, sIL-6R and TNF-alpha) in serum of the aspirated bone marrow has no advantage to analysis of the peripheral blood serum.