[Show abstract][Hide abstract] ABSTRACT: We analyzed 1156 multiple myeloma (MM) patients treated with thalidomide. The overall response rate was 63.6%, with complete remission in 13.4%. Combined regimens had better outcomes than thalidomide plus dexamethasone or single agent thalidomide. Thalidomide was not able to overcome adverse cytogenetics. Superior results were seen in patients undergoing subsequent autologous stem cell transplantation. The rate of adverse events was low. Thalidomide has a strong potential to improve response and survival measures in patients with standard risk MM. Combined regimens should be used, with lower doses of thalidomide. High risk myelomas should be treated individually.
[Show abstract][Hide abstract] ABSTRACT: Autologous stem cell transplantation (ASCT) became standard of care for patients with multiple myeloma (MM) under the age of 65 years. We routinely perform ASCT for newly diagnosed MM since 1996 in our department.
We retrospectively analyzed all 285 transplants in 185 patients done for MM from January 1996 till December 2010. We analyzed overall survival (OS) and progression-free survival (PFS) regarding conditioning, stage, complete or very good partial remission (CR, VGPR) achievement, renal impairment, single vs. double transplant.
Estimated 10-years survival of the whole set of patients is 39% (median survival 95 months). Patients with renal impairment show same OS as those without (p = 0.22). Patients show similar overall survival and event free survival regardless of type of transplant. We observed better outcome in terms of overall survival in patients treated with new drugs (p = 0.0014). Reaching CR or VGPR was not translated into better OS (p = 0.30) and EFS (p = 0.10). Also stage of the disease and whether single or double transplant was used did not make any significant difference in the outcome.
Stem cell transplantation greatly improved outcome of patients with MM. Poor outcome of allogeneic transplantation in our group of patients is related to high transplant related mortality (20% vs. 0%) and unexpected high relapse rate. There is a trend towards better survival, when new drugs are incorporated at any time in the course of the disease. This fact supports hypothesis that use of these drugs with ASCT should translate into better long-term outcome.
Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové 01/2013; 56(1):9-13.
[Show abstract][Hide abstract] ABSTRACT: Venous thromboembolism (VTE), with the subsequent risk of pulmonary embolism, is a common adverse effect of thalidomide treatment in patients with multiple myeloma (MM). In our retrospective study, we analyzed candidate single-nucleotide polymorphisms (SNP), CINP (rs7011), CETP (rs289747), ALDH1A1 (rs610529), CDKN1A (rs3829963), GAN (rs2608555), vascular endothelial growth factor (rs699947), and ALDH1A1 (rs168351), previously identified in a large association study based on the hypothesis-driven candidate gene approach nominated by the International Myeloma Foundation "Bank On A Cure" (3404 SNPs). In that study, the researchers built a classification tree that enables prediction of individual risk of VTE in patients with MM.
Genotypes of these SNPs were determined in an independent cohort of 111 patients with MM through TaqMan real-time polymerase chain reaction (PCR) allelic discrimination and were used for prediction of individual VTE risk.
The results of this study did not confirm the ability of this classification tree to predict VTE risk in patients with MM from the Czech Republic; of these patients, 21 (19%) developed high-grade VTE. However, in patients with VTE, we found higher frequency of the AC genotype in the CDKN1A gene (42.9% vs. 16.7%; odds ratio 3.64) in comparison with the CC genotype (P = .015). SNPs of other genes as well as age and sex of the patients had no statistically significant influence on the risk of VTE.
Further studies are needed to confirm the initial analysis that provided predictive information of genetic variations in patients with myeloma that may influence risk of VTE.
[Show abstract][Hide abstract] ABSTRACT: Only a few cases of pneumocystis pneumonia (PCP) in Cushing's syndrome have been published in the literature so far. In the majority of these patients, the pneumonia occurred after reduction of the hypercortisolism with medicamentous treatment. We report two cases of PCP during conservative treatment of hypercortisolism. We describe clinical, imaging and laboratory findings in two patients and review published cases of pneumocystits pneumonia in Cushing's syndrome. A 60-year-old woman and 20-year-old man with Cushing's syndrome due to ectopic ACTH syndrome were treated at our department. Both developed pneumocystis pneumonia early after treatment with ketoconazole and ethomidate bromide had been introduced and the levels of cortisol rapidly decreased. PCP prophylaxis in patients with high cortisolemia should be started before treatment of hypercortisolism in current practice. Gradual lowering of plasma cortisol should also reduce the risk of infection by Pneumocystis jiroveci.
Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové 01/2011; 54(3):127-30.
[Show abstract][Hide abstract] ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is a precancerosis comprising two different kinds of cancer: lymphoid/lymphoplasmocytoid MGUS and plasma cell MGUS that represents about 85% of all MGUS cases. This type of MGUS has low but persistent tendency to transform to malignant disease, mainly multiple myeloma (MM), with frequency of about 1% per year. Using known risk stratification models based on clinical parameters, it is possible to identify patients' groups with average rates of progression as low as 0.26% and as high as 12% per year. However, due to the lack of clear genetic and/or phenotypic markers distinguishing MGUS from MM, we are not able to predict if and when MGUS will progress to MM in individual patients. There are partially overlapping molecular pathogenic events shared by MGUS and MM. Better understanding of pathogenesis of MGUS and MM using molecular-genetic approaches will help disclose the mechanisms of myeloma genesis; it can be also useful for identification of novel molecular targets. The ultimate goal for the near future is to develop better markers for definition of high-risk MGUS patients who will be candidates for early treatment intervention.
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 01/2011; 24 Suppl:S14-7.
[Show abstract][Hide abstract] ABSTRACT: Immunoglobulin D (IgD) multiple myeloma (MM) is a rare plasma cell disorder constituting less than 2% of all MM cases. Survival of patients with IgD MM is generally shorter than that of patients with other types of monoclonal (M-) protein. We have retrospectively analyzed patients with IgD MM participating in clinical trials of the Czech Myeloma Group. Twenty-six IgD MM patients treated between 1996 and 2006 were identified, 14 (54%) men and 12 (46%) women. The median age was 61 years (range: 37-79 years). Ten of 26 patients (39%) were treated with first-line high-dose chemotherapy (HDCT) using melphalan 200 mg/m(2) followed by autologous stem cell transplantation (ASCT). Thirteen of 26 patients (50%) received conventional chemotherapy (CHT), mostly melphalan and prednisone or a vincristine/doxorubicin/dexamethasone (VAD) regimen. Treatment responses were evaluable for 23 of 26 (89%) patients. All HDCT patients had treatment responses, including seven patients (70%) with complete responses and three patients (30%) with partial responses. The median progression-free survival was 18 months for HDCT patients and 20 months for CHT patients. The median overall survival (OS) for all patients was 34 months. The median OS for the HDCT group has not yet been reached (70% of the patients are still alive). In contrast, the median OS for CHT patients was only 16 months. The difference in OS between the two groups was statistically significant (P=0.005). In conclusion, the overall response rate for patients with IgD MM aged 65 years or less treated with HDCT and ASCT is similar to that seen in other MM types.
Bone Marrow Transplantation 02/2008; 41(1):51-4. · 3.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS) is the most common type of monoclonal gammopathies. Genetic changes, various cytokines and bone marrow angiogenesis play an important role in the pathogenesis. As far as the malignant transformation of MGUS is concerned, size and type of the serum M-protein, serum kappa and lambda free light chain ratio and number of plasma cells in peripheral blood seem to play a predictive role. A new possible risk-stratification model predicting progression of MGUS to multiple myeloma or other related disorders was presented in 2006. The model takes three parametres in consideration, type and initial size of the serum M-protein and serum kappa and lambda ratio. Patients are divided into four risk groups with different risk of progression, from 5% at 20 years in low risk group to 58% in high risk group. The interval from MGUS diagnosis to the evolution of multiple myeloma or other related malignancies ranges from 1 to 30 years. Nevertheless, the risk of progression persists even after more than 30 years after MGUS diagnosis.
Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti 02/2008; 21(4):160-4.
[Show abstract][Hide abstract] ABSTRACT: Thalidomide is an immunomodulatory drug used in the treatment of relapsed or refractory multiple myeloma (MM). The optimal dosing regimen of thalidomide is not known.
We retrospectively analysed the overall response rate and response duration of 53 patients with relapsed MM who received thalidomide in a median dose of 100 mg daily. The aim of the study was to compare the response rates of thalidomide given as the second-line treatment to those of thalidomide given as the third-line therapy.
Of 33 patients receiving thalidomide as second line, 13 (39%) had overall treatment response. Of 20 patients treated with thalidomide monotherapy as the third-line treatment, there were three treatment responses (15%) (P = 0.039). The median duration of treatment response in the second-line thalidomide group (12 months, range 6-60 months) was twice as long as that in the third-line thalidomide group (6 months, range 3-57 months), although the difference was not statistically significant, probably due to low number of patients. Only 6% of patients (3/53) had to stop the treatment because of toxicity.
Monotherapy with low-dose thalidomide results in treatment responses in approximately 30% of patients with advanced MM. The response rate appears to be higher if thalidomide treatment is started after the first relapse or progression in comparison with the second relapse or progression. Treatment toxicity is acceptable even with prolonged exposure to the drug.
European Journal Of Haematology 11/2007; 79(4):305-9. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thalidomide is one of the drugs which are newly used in the therapy of multiple myeloma. Its immunomodulating action and a number of additional effects have been proven in the treatment of advanced and refractory stage of the disease. However, the best dosing scheme has not yet been discovered and is the subject of research in a number of clinical studies today.
On a retrospective basis, we evaluated results for 59 patients with multiple myeloma who were treated with thalidomide in our facility (median dose of 100 mg), in monotherapy or in combination with corticosteroids, between 2000 and 2005. The objective was to determine the percentage of responses to treatment in patients at different stages of the disease. Response to treatment was evaluated in accordance with EBMT standards.
Thalidomide was used as 2nd line therapy (1st relapse or primarily resistant disease) in 59% of cases (35 patients), and as 3rd line therapy (2nd relapse) in 37 % of cases (22 patients). 2 patients were receiving thalidomide as 4th line therapy. None of the patients had taken thalidomide as part of previous treatment. The response rate at 1st relapse (CR - complete remission, PR - partial remission, MR - minimum response) was 60% (21 patients), of which CR was recorded in 2 patients (6%), PR was recorded in 12 patients (35%) and MR in 6 patients (17%). The response rate at 2nd relapse was 45% (10 patients), of which CR was recorded in 3 patients (14%), PR in 1 patient (5%) and MR in 5 patients (23%). Even though we did not record any statistically significant difference in the response of the evaluated group of patients to the treatment with thalidomide at 1st and 2nd relapse, a higher percentage or progression during treatment (32% vs. 14%) was observed in patients at 2nd relapse. 2 patients treated with thalidomide at 3rd relapse did not have a satisfactory response to the treatment (progression or short stabilisation of the disease with subsequent progression). Only 3 patients (5%) of the evaluated group had to discontinue the treatment due to severe adverse events (neuropathy, allergic reaction, leukopenia). The follow up time for Thalidomide therapy ranged between 3 and 62 months for both groups (with a median of 10 months) and spanned from 3 to 60 months at 1st relapse (median of 12 months) and from 3 to 57 months at 2nd relapse (median of 6 months). No statistically significant differences were observed between the 1st and 2nd relapse groups of patients in terms of response rates or length of effect.
Thalidomide is highly efficient in the treatment of multiple myeloma. The results of study document effectiveness of thalidomide regardless of the disease stage. Comparison of study data with the results of other studies shows that the effectiveness of lower doses we used is comparable with that of higher doses. The fact that lower doses of thalidomide reduce the incidence of adverse events is a clear advantage.
[Show abstract][Hide abstract] ABSTRACT: Switching of the paraprotein isotype or transient presence of oligoclonal bands detectable by serum immunofixation electrophoresis has been reported following not only transplantations, but also after intensive chemotherapy for leukemia. Retrospective analysis of 72 transplanted myeloma patients was carried out to determine the frequency and clinical significance of the appearance of abnormal proteins bands (APB) distinct from the original paraprotein. APB presence was observed in 31 patients (43%) already after the first autotransplant, the median interval from transplant was 2 months (range, 1 to 6 months). The most frequent occurrence of APB was observed after allogeneic transplantation. In the group of patients with APB presence more patients achieved complete remission (32.2% versus 17.1%), statistically significant differences were also established when we compared the percentage of surviving patients and overall survival, to the present date, among both groups of patients (p=0.03). All relapsed patients with previous isotype class switching had disease characterized by the same type of paraprotein as that detected at diagnosis. The development of APB is likely related to the recovery of impaired immunoglobulin production after transplantation. We confirmed favourable prognostic significance of this finding in transplanted myeloma patients.
[Show abstract][Hide abstract] ABSTRACT: Registr monoklonálních gamapatií (RMG) představuje spolu s programem CRAB zamě-řeným na zlepšení časné diagnostiky nemoc-ných s mnohočetným myelomem dva hlavní současné projekty České myelomové skupiny (CMG). Oficiálně byl představen u příležitosti každoročního setkání CMG ve Velkých Bílovicích v dubnu 2007. Důvodem pro jeho vytvoření byla snaha o zahájení prospektivního monitoringu dat nemocných s monoklonálními gamapatie-mi z regionu střední a východní Evropy s cílem sledování jejich incidence, využívání a efektu jednotlivých léčebných modalit včetně výskytu nežádoucích příhod a toxicity v podmínkách běžné klinické praxe. Předpokladem je spolu-práce významných center zabývajících se danou tématikou v regionu centrální a východní Evropy tak, aby mohlo být dosaženo kritického množ-ství hodnocených parametrů. Aktuální stav databáze a počty nemocných v jednotlivých skupinách spolu s přehledem jednotlivých spolupracujících center shrnuje obrázek 1. Od 1. 5. 2007 do současné doby zadává data do registru již celkem 17 center spolupracujících v rámci CMG, dnes se již opravdu jedná o mezinárodní databázi, pro-tože kromě 15 center z České republiky jsou aktivní i 2 hlavní centra Slovenské republiky a plánuje se možnost případného připojení dalších center Slovenské republiky, ale event. i Polska a Maďarska po vyřešení smluvních vztahů s CMG. K datu 4. 4. 2011 bylo již v RMG registrováno celkem 3 254 nemocných s mono-klonálními gamapatiemi, z toho bylo 1895 ne-mocných s mnohočetným myelomem a 1359 nemocných s MGUS. Vstup do databáze je umístěn na webových stránkách CMG – České myelomové skupiny (www.myeloma.cz) pod ikonou Registr RMG. Po její volbě se otevře základní stránka registru, která je zobrazena na obrázku 2. Ta umožňuje 1 II. interní klinika – OKH, LF UK a FN Hradec Králové 2 Institut biostatistiky a analýz, MU Brno 3 Interní hematoonkologická klinika FN Brno 4 Česká myelomová skupina Registr monoklonálních gamapatií představuje spolu s programem CRAB dva hlavní současné projekty České myelomové skupiny. Důvo-dem pro jeho vytvoření byla snaha o zahájení prospektivního sledování dat nemocných s monoklonálními gamapatiemi z regionu střední a východní Evropy s cílem sledování jejich incidence, využívání a efektu jednotlivých léčebných modalit včetně výskytu nežádoucích příhod a toxicity. Jde o ambiciózní projekt i ve světovém měřítku, který by měl do budoucna vést k dalšímu zlepšení péče o nemocné. Klíčová slova: monoklonální gamapatie, registr, mnohočetný myelom, diagnostika, léčba.