INTRODUCTION: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition with a risk of malignant conversion. PATIENTS AND METHODS: With the aim to estimate the cumulative risk MGUS progression to hematologic malignancies, we analyzed a nationwide population-based cohort of 1887 MGUS patients from the Czech Registry of Monoclonal Gammopathies (RMG) between 2007 and 2013. RESULTS: During the follow-up period (median 4 years; range 0.6-34.8), progression to hematologic malignancies was observed in 8.6% (162 of 1887) of patients. Factors associated with progression were as follows: M-protein concentration ≥1.5 g/dL, pathological sFLC (<0.26 or >1.65) ratio, bone marrow plasma cells (BMPCs) in cytology >5%, immunoparesis, age ≥69 years, and the level of serum hemoglobin at baseline <12.0 g/dL. Combining these factors, we propose a new risk model (CMG model). The risk of progression at 10 years was 1.6%, 16.9%, 22.9%, 39.4%, and 52.3%, respectively, if 0 (reference group), one, two, three, or four to five risk factors are present (P<.001) with HR 63 times higher compared to the reference MGUS group. CONCLUSION: The new CMG model was established with an advantage for better identification of MGUS patients at low risk.

• Klíčová slova
• monoclonal gammopathy, multiple myeloma, progression, risk factors,
• MeSH
• biologické markery MeSH
• hodnocení rizik MeSH
• hybridizace in situ fluorescenční MeSH
• Kaplanův-Meierův odhad MeSH
• kostní dřeň patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální gamapatie nejasného významu diagnóza   epidemiologie   metabolismus   MeSH
• myelomové proteiny metabolismus   MeSH
• nádorová transformace buněk MeSH
• plazmatické buňky metabolismus   patologie   MeSH
• progrese nemoci MeSH
• proporcionální rizikové modely MeSH
• registrace MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• surveillance populace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• biologické markery MeSH
• multiple myeloma M-proteins MeSH Prohlížeč
• myelomové proteiny MeSH

OBJECTIVE: Subcutaneous (SC) application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM) patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM) patients treated using either intravenous (IV) or subcutaneous (SC) route of administration. PATIENTS AND METHODS: During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly - 63% or twice weekly - 27%) in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration. RESULTS: The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥ 3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN). PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥ 2 was present in 20% vs 18% and PN grade ≥ 3 was present in 6% vs 4%. CONCLUSIONS: We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.

• MeSH
• bortezomib škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• incidence MeSH
• indukce remise MeSH
• injekce intravenózní MeSH
• injekce subkutánní MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   MeSH
• nemoci periferního nervového systému epidemiologie   etiologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bortezomib MeSH

The prognostic impact of chromosomal abnormalities was evaluated by fluorescence in situ hybridization with cytoplasmic immunoglobulin light chain staining (cIg-FISH) and by classical metaphase cytogenetics in a cohort of 207 patients with newly diagnosed multiple myeloma who were treated with high-dose therapy followed by autologous stem cell transplantation in the CMG2002 clinical trial. The incidence of chromosomal abnormalities detected by FISH was as follows: 52.7% for del(13)(q14), 6.5% for del(17)(p13), 18.6% for t(11;14)(q13;q32), 22.8% for t(4;14)(p16;q32) and 45.7% for gain(1)(q21). Metaphase cytogenetic analysis revealed a complex karyotype in 19.1% and hyperdiploidy in 21.7% of patients. The overall response rate was not influenced by the presence of any studied chromosomal abnormality. Patients with a complex karyotype, those with translocation t(4;14) and those with gain of the 1q21 locus had a shorter time to progression (TTP) and overall survival (OS). Other genomic changes such as translocation t(11;14) and del(13q) had less impact on TTP and OS. In multivariate analysis, complex karyotype, translocation t(4;14) and β(2)-microglobulin level > 2.5 mg/L were independent prognostic factors associated with poor overall survival. Their unfavorable prognostic impact was even more pronounced if they were present in combination. Patients with t(4;14) present together with a complex karyotype had the worst prognosis, with a median OS of only 13.2 months, whereas patients with a normal karyotype or karyotype with ≤ 2 chromosomal changes had the best outcome, with 3-year OS of 85.9%. In conclusion, complex karyotype, gain of 1q21 region and translocation t(4;14) are major prognostic factors associated with reduced survival of patients with newly diagnosed multiple myeloma treated with autologous stem cell transplantation.

• MeSH
• autologní transplantace MeSH
• chromozomální aberace MeSH
• cytogenetické vyšetření MeSH
• dospělí MeSH
• incidence MeSH
• karyotypizace * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 14 * MeSH
• lidské chromozomy, pár 4 * MeSH
• míra přežití MeSH
• mnohočetný myelom diagnóza   genetika   mortalita   terapie   MeSH
• prognóza MeSH
• senioři MeSH
• translokace genetická * MeSH
• transplantace hematopoetických kmenových buněk MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

BACKGROUNDS: Patients with multiple myeloma have a high risk of venous thromboembolism (VTE), especially during the induction chemotherapy. The aim of our observational study was to determine the impact of prophylaxis with low molecular weight heparin (LMWH) on the incidence of thromboembolic complications. PATIENTS AND METHODS: We analyzed the incidence of thromboembolic events in 258 patients treated with induction chemotherapy containing vincristin, doxorubicin or idarubicin, and dexamethasone, followed by stimulation chemotherapy with cyclophosphamide and G-CSF, and high-dose chemotherapy with melphalan. Two groups of these patients were compared based on the practice of thromboprophylaxis. Patients in the first group (Control, n = 140) were either not treated or treated with a short duration of anticoagulation therapy while the patients in the second group (Prophylactic, n = 118) underwent standard prophylaxis with LMWH throughout the entire period of induction chemotherapy. A total of 102 patients were selected for a close monitoring of the prophylactic effect of different LMWH doses and to be compared to patients without treatment. RESULTS: Standard prophylaxis with LMWH significantly (p < 0.007) lowered a risk of VTE when compared to patients without such prophylaxis (3.4% versus 12.9%, respectively). Furthermore, analysis of the subgroup of 102 patients revealed that higher LMWH doses (> 70 IU/kg per day) achieved full prophylaxis in 28 patients while lower doses were less effective leading to DVT in 3 (7.7%) out of 39 patients. In contrast, VTE was diagnosed in 5 (14.3%) out of 35 patients without any LMWH prophylaxis. CONCLUSION: Prophylaxis with LMWH leads to a significant reduction of the risk of thromboembolic complications during the induction chemotherapy in patients suffering from MM. The prophylactic effect of LMWH is dose-dependent.

• MeSH
• antitumorózní látky škodlivé účinky   terapeutické užití   MeSH
• heparin nízkomolekulární terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom komplikace   farmakoterapie   MeSH
• rizikové faktory MeSH
• žilní trombóza etiologie   prevence a kontrola   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• heparin nízkomolekulární MeSH

The study aimed at evaluating the relation of 7 parameters associated with the internal biological properties of myeloma cells and the bone marrow microenvironment to multiple myeloma (MM) stages, distinguishing its initial/asymptomatic phase from monoclonal gammopathy of undetermined significance (MGUS) and assessing their relation to myeloma prognosis. In the studied group comprising 286 individuals (89 MGUS and 179 MM patients), statistically significant differences (Mann-Whitney test) between MGUS and MM at the time of diagnosis were found in the serum levels of HGF (hepatocyte growth factor), VEGF (vascular endothelial growth factor), ICTP (intercellular - carboxy-terminal telopeptide of type I collagen), PINP (procollagen type I N-terminal propeptide), OPG (osteoprotegerin) and syndecan-1/CD138, but not in Fas. Multivariate analysis (logistic regression) revealed an unsatisfactory potential of all the 7 studied indicators to discriminate between MGUS and MM. A deeper analysis showed statistically significant differences between MGUS and the initial/asymptomatic phase of MM (stage 1 according to the International Staging System) only in the cases of syndecan-1 (p=0.001) and Fas (p=0.008). The assessment of initial values of HGF, VEGF, ICTP, PINP, OPG, syndecan-1 and Fas showed a statistically significant relation (log rank test) to the overall survival (OS) in a group of 132 patients treated with conventional chemotherapy only in the cases of syndecan-1 (p=0.0002) and Fas (p=0.018), but in none of the investigated parameters in a group of 74 patients treated with HDT/ASCT (high-dose therapy/autologous stem cell transplantation). The analysis showed that, despite significant differences in serum levels of 6 of the 7 studied parameters found between MGUS and MM, none of the markers may be included in the spectrum of indicators used to distinguish the two conditions. Despite the positive relation, especially of syndecan-1 and, to a lesser extent, of Fas to the OS in patients treated with conventional chemotherapy, these prognostic factors are not applicable to HDT/ASCT.

• MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• ELISA MeSH
• hepatocytární růstový faktor krev   MeSH
• kolagen typu I MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom krev   diagnóza   MeSH
• monoklonální gamapatie nejasného významu krev   diagnóza   MeSH
• nádorové biomarkery krev   MeSH
• osteoprotegerin krev   MeSH
• peptidové fragmenty krev   MeSH
• peptidy MeSH
• prognóza MeSH
• prokolagen krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• syndekan-1 krev   MeSH
• vaskulární endoteliální růstový faktor A krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• hepatocytární růstový faktor MeSH
• HGF protein, human MeSH Prohlížeč
• kolagen typu I MeSH
• nádorové biomarkery MeSH
• osteoprotegerin MeSH
• peptidové fragmenty MeSH
• peptidy MeSH
• procollagen Type I N-terminal peptide MeSH Prohlížeč
• prokolagen MeSH
• SDC1 protein, human MeSH Prohlížeč
• syndekan-1 MeSH
• TNFRSF11B protein, human MeSH Prohlížeč
• vaskulární endoteliální růstový faktor A MeSH
• VEGFA protein, human MeSH Prohlížeč

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (AT) is accepted as first-line therapy for patients with multiple myeloma (MM), with very good tolerance and low mortality (2-3%). STUDY DESIGN: We tested repeated transplantation with different experimental maintenance therapies in patients with MM relapsing/progressing after first AT. Results were compared using intra-individual analyses, therefore inter-individual differences are excluded (T2 model). PATIENTS AND METHODS: Between January 1997 and January 2003, 32 patients with relapsing/progressing MM after first AT were included in the pilot study, median follow-up was 75.2 months. They received the following experimental therapies: IL-2-activated PBSC (10 pts), pamidronate (4 pts), thalidomide (15 pts), consolidation chemotherapy CED (3 pts). RESULTS: Sensitivity to C-VAD reinduction chemotherapy (4 cycles) was 50%, response to the second AT compared to the first was better in 7, the same in 16 and worse in 9 patients. Toxicity of the first and second transplantation was similar and usually did not exceed grade II (SWOG). Transplant-related mortality was 3% (1/32). Event-free survival after second AT (EFS II) is known in 22 patients; 7 have achieved prolongation of EFS II versus EFS I. In the whole group median EFS I was 15.7 months, median EFS II was 12.9 months, median overall survival (OS) was 79.1 months; 20/32 patients were alive at the time of analysis. CONCLUSIONS: Repeated AT is a feasible and successful strategy in treatment of relapsing MM; response to second AT and toxicity were acceptable and similar to the first AT in our assessment.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   epidemiologie   chirurgie   MeSH
• mnohočetný myelom farmakoterapie   epidemiologie   chirurgie   MeSH
• pilotní projekty MeSH
• přežití po terapii bez příznaků nemoci MeSH
• rejekce štěpu farmakoterapie   epidemiologie   chirurgie   MeSH
• senioři MeSH
• studie proveditelnosti MeSH
• terapie neúspěšná MeSH
• transplantace kmenových buněk metody   statistika a číselné údaje   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• antitumorózní látky MeSH

INTRODUCTION: The aim of this study was the retrospective assessment of therapy results and the changing prognosis of multiple myeloma (MM) patients from the Middle and North Moravia region of the Czech Republic during the last 40 years. PATIENTS AND METHODS: The analyzed group of 562 patients was gathered in the years 1959-2000, mean age 63 (28-91) years, M/F ratio 1.1 : 1.0. Overall survival (OS) curves were plotted according to the method of Kaplan and Meier and compared using the log rank test (P<0.05). RESULTS: During the long assessed period, a significant change in prognosis and therapy response was achieved (P=0.0000). The 'first turning point' (1963-1975) characterized by unsystematic melphalan and prednisone therapy (MP), led to significant improvement of OS (8-19 months, P=0.0031) in comparison with the period of plain symptomatic therapy (1959-1963) and the increase in 3-year survival rate from 4 to 23% of patients. The 'second turning point' (1976-1980), characterized by introduction of the systematic conventional polychemotherapy (VMP, VMCP, VBAP, VCAP) and complex supportive treatment, was associated with subsequent improvement of therapeutic response (OS 40 months, P=0.0000; 3- or 10-year survival was seen in 55 and 5.5% of patients). Nevertheless, the results of the next 20 years (regimens VB(C)MCP, VAD, Cy-VAD and CIDEX) are a little disappointing with insignificant progress. In the whole group of 295 patients from the years 1976 to 1995, divided into 5-year periods, remission (R< or =25% of the initial M-protein level) was achieved in 10-24% of cases, the OS median was 32-44 months, and 5 (respectively 10)-year survival improved from 25 to 36% and from 5.5 to 16.5% of patients. The 'third turning point' represented years 1996-2000 marked with the introduction of high dose (HD)-therapy with ASCT support leading in a group of 31 patients (< or =65 years) to remission in 71%, to complete remission in 32% and to significant improvement of OS (P=0.0037) and 5-year survival in 91% of the patients. The improvement of therapy results in this 'third turning point' was demonstrated in comparison with the 1976-1995 group with conventional therapy with a group of patients from 1996 to 2000 (both conventional and HD therapy with ASCT), characterized by 36% of remissions and 5-year survival of 57% of the patients (P=0.030). HD therapy with ASCT achieved in the years 1996-2000 had better therapy results (R-71%, 5-year survival 91%) than that achieved in two comparable groups of patients (1991-1995 and 1996-2000), fulfilling all criteria of HD therapy with ASCT but treated with conventional therapy only (R - 24 and 32%, 5-year survival 46 and 68% of the patients). CONCLUSION: The retrospective analysis showed that the meaningful change in overall prognosis of MM patients achieved in Moravia is in accord with worldwide trends in the course of 1959-2000 years, which was achieved due to the gradual application of the modern innovated systems of complex therapy.

• MeSH
• analýza přežití MeSH
• autologní transplantace MeSH
• dospělí MeSH
• indukce remise MeSH
• kombinovaná terapie mortalita   statistika a číselné údaje   trendy   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom mortalita   terapie   MeSH
• prognóza MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Questionnaires on the quality of life and tolerance of different parts of maintenance treatment were sent to a total of 83 patients with multiple myeloma. All patients were for more than one year on maintenance treatment which involved either interferon alpha monotherapy (I), 3 million u. three times per week till signs of relapse developed or sequence administration of interferon alpha and dexamethazone 40 mg on day 1 to 4, 10 to 13 and 20 to 23 and then after a four-week interval again interferon alpha, again till progression of the disease occurred. The patients evaluated the presence or absence of different undesirable effects of treatment during the first two weeks of treatment and throughout the year and listed their intensity into four categories defined in the questionnaire. The quality of life was evaluated by means of a basic module of the questionnaire of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30). The results of the questionnaire are to a certain extent surprising as from the patients' answers ensues that this maintenance treatment is associated with more numerous undesirable effects than the physicians realized when in contact with the patient. In this summary we can list only the most frequent effects (deterioration of eyesight, impaired sleep, depressions, irritability and unrest, chill, pain in muscles and joints, general weakness and dyspnoea). From the questionnaires on the quality of life ensues a markedly poorer quality of life of these patients as compared with the healthy population. There are however no basic differences between individual groups. The questionnaires were handed only to patients who had maintenance treatment for more than one year and thus patients were eliminated where maintenance treatment was discontinued because of undesirable effects. To give a general idea of the tolerance of the above maintenance treatment the authors mention that to the date of Aug. 31, 2001 113 patients were randomized into one of the branches of maintenance treatment. Maintenance treatment had to be discontinued in 6% patients (in two instances on account of severe hypothyroidism, in one case on account of hallucinations, in three instances on account of severe mental depression caused by this treatment). Reduction of interferon doses in 20% patients usually because of cytopenia but also on account of psychic problem. To the question what length of prolongation of life compensates the undesirable effects of maintenance treatment the following replies were obtained from patients receiving ID, possibly I: 3 months--47.6 and 38.3%, 6 months--4.3 and 10.6%, 9 months--0 and 4.3%, 12 months--47.6 and 46.8% of the addressed patients. In reply to the question whether the patients would prefer, assuming equal effectiveness, a maintenance monotherapy with interferon alpha or dexamethazone more patients preferred interferon to dexamethasone. For practice ensues from this article informing on undesirable effects of maintenance treatment and the effect of maintenance treatment on the quality of life: 1. the necessity of thorough knowledge of physicians of all possible undesirable effects as only a doctor knowing possible undesirable effects of treatment can recognize them, 2. regular monitoring not only of the activity of the basic disease, but also undesirable effects of maintenance treatment and the influence of treatment on the patients' quality of life, 3. the necessity to assess the quality of life in clinical trials as an important parameter for deciding on the way of treatment.

• MeSH
• antitumorózní látky škodlivé účinky   terapeutické užití   MeSH
• dexamethason škodlivé účinky   terapeutické užití   MeSH
• interferon alfa-2 MeSH
• interferon alfa škodlivé účinky   terapeutické užití   MeSH
• kvalita života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom farmakoterapie   chirurgie   MeSH
• průzkumy a dotazníky MeSH
• rekombinantní proteiny MeSH
• transplantace hematopoetických kmenových buněk MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antitumorózní látky MeSH
• dexamethason MeSH
• interferon alfa-2 MeSH
• interferon alfa MeSH
• rekombinantní proteiny MeSH