Biomedical subjects

J Bacovský

Publications and source records attributed to J Bacovský.

At least 19 recordsLinked to original sources

PubMed2006

[Comparison of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma].

PURPOSE OF STUDY: The study focuses on evaluation of differences in serum levels of selected biological indicators in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM), primarily from the viewpoint of potential asset to clinical practice. PATIENTS AND METHODOLOGY: The analyse set of 96 patients consisted of 30 individuals with MGUS and 66 patients with MM examined in the context of the disease diagnosis before therapy commencement. Serum levels of the assessed parameters were examined with the help of radio-enzymatic method (thymidinkinase), radioimmunoanalysis (beta2-micro-globulin, ICTP, PINP), enzymoimmunoessay method (sIL-6R, sVCAM-1, sICAM-1, sOPG and sRANKL) and the technique of quantitative sandwich enzymatic immunoessay (sHGF, sVEGF, bFGF, syndecan-1/CD138 and sFas). Statistical examination was performed by Pearson and Fischer test, chi2-test, or nonparametric U-test pursuant to Mann-Whitney (p < 0.05). RESULTS: Statistically significant differences were found between MGUS and MM in the case of serum level comparisons of sIL-6R (p = 0.02), ICTP (p = 0.001), sHGF (p = 0.001) and syndecan-1/sCD138 (p = 0.001), while no statistically significant differences were present in the case of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas. During the analysis of frequency of occurrence of abnormal values in the MM and MGUS groups, significant differences were found not only in the case of standard parameters, such as beta2-microglobulin, thymidinkinase, creatinin and albumin, but also in the case of sIL-6R, ICTP, sHGF and syndecan-1, but not in comparisons of the levels of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas. Attempts at examination of serum levels of sRANKL and soluble form of bFGF failed as too low values were measured. CONCLUSION: The analysis of behaviour of the 10 parameters, mostly intimately related to biological properties of clonal plasmatic cells or to changes of microclimate of bone marrow, effectively contributed to distinction between MGUS and MM only in the case of serum levels of sIL-6R, ICTP, sHGF and syndecan-l (sCD138), i.e. indicators with demonstrable relevance for MM prognosis assessment.

Adult↗

PubMed2004

Second autologous transplantation for multiple myeloma patients relapsing after the first autograft -- a pilot study for the evaluation of experimental maintenance therapies. Report of the prospective non-randomized pilot study of the Czech Myeloma Group.

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.

Adult↗

PubMed2002

[Quality of life and tolerance of maintenance therapy in patients with multiple myeloma].

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.

Antineoplastic Agents↗

PubMed2002

[Therapeutic results and changes in prognosis in patients with multiple myeloma in central and northern Moravia over the past 40 years].

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.

Adult↗

PubMed2001

[Autologous transplantation of peripheral hematopoietic cells and subsequent maintenance therapy with interferon alpha or interferon alpha and dexamethasone in patients with multiple myeloma--results from the 4W randomized clinical trial of the Czech Myeloma Group].

In the clinical 4W study patients with newly diagnosed multiple myeloma are included where the state of the disease calls for treatment, while high dose chemotherapy is not contraindicated. Treatment according to protocol 4W comprises induction chemotherapy VAD, mobilization of haematopoietic cells (cyclophosphamide 5 g/m2). This is followed by autologous transplantation (as a conditioning regime melfalan 200 mg/m2 is administered). The patients are randomized into two groups, the first one is given interferon alpha as maintenance treatment, in the second group alternates cyclically interferon alpha and dexamethasone treatment. So far between 1996 and Aug. 31 2000 in the 4W clinical study 167 patients were included. 113 patients after transplantation were evaluated incl. 13 (12%) who achieved complete remission of the disease (absence of paraprotein, negative immunofixation), 63 patients (56%) with remission of the disease (decline of paraprotein, by more than 75%). Another 24 patients (21%) achieved partial remission (decline of paraprotein by more than 50% but less than 75%). The peritransplantation mortality is 2.67%. So far there is no significant difference between the two groups on maintenance treatment as regards the mean period before a relapse of the disease (p = 0.567). The median of the mean survival was not reached so far. The authors describe the results of the internal analysis of data incl. statistical processing.

Adolescent↗

PubMed2001

[Magnetic resonance in examination of the spine in patients with multiple myeloma].

Multiple myeloma (MM) is a malignant disease of the haematopoietic system characterized by the formation of osteolytic foci of the skeleton with predilection of the thoracolumbar portion of the spine. The submitted investigation evaluates the importance of examination of the spine by magnetic resonance (MR), as compared with results of conventional radiology (CR). The analyzed group of 75 patients with multiple myeloma was assembled in the course of the previous four years. All patients were examined by conventional radiology and magnetic resonance and the assembled results were mutually compared. On examination by MR a pathological finding was recorded in 68/75 (91%) patients, when using CR in 41/75 (55%) patients. Compression of the vertebral bodies was assessed by means of magnetic resonance in 42/75 (56%) patients, when using CR in 37/75 (49%) patients. Secondary stenosis of the spinal canal was detected by MR in 23/75 (30%), extramedullary spread of myelomatous masses was found in 15/75 (20%) patients whereby radiographic examination was negative in these patients. Osteolytic foci in the area of the spine were recorded in 62/75 (83%) patients examined by MR, while by using CR only in 3/75 (4%). From the presented results ensues that nuclear magnetic resonance is for evaluation of spinal lesions in MM much more sensitive than conventional radiography, mainly due to the possibility of direct visualization of soft tissue tumourous masses and evaluation of their relationship to the spinal canal. The contribution of MR examination is invaluable in particular in patients with obscure back pain and a negative finding on radiographic examination of the skeleton where X-ray examination does not explain adequately the patient's complaints, as well as in patients with suspected compression of the spinal cord. In some liminal situations it contributes to more accurate assessment of the clinical stage and thus to selection of adequate treatment.

Adult↗

PubMed2000

[Relation of serum levels of the soluble cytoadhesion molecules sVCAM-1 and sICAM-1 to selected factors in the cytokine network in multiple myeloma].

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.

Cytokines↗

PubMed1999

Single photon bone densitometry in multiple myeloma.

The study was performed in 45 patients with multiple myeloma. There was found significant correlation between diminished bone mineral density of forearm and duration of the disease. No correlation between bone mineral density and biochemical markers of osteolysis (pyridinoline and deoxypyridinoline in urine) and serum levels of cytokines was found.

Absorptiometry, Photon↗

PubMed1999

[Relation of the soluble cytoadhesion molecules VCAM-1 and ICAM-1 to selected clinical and laboratory indicators in multiple myeloma].

Hitherto conducted studies concerned with the problem of cytoadhesive molecules (CAM) dealt only in a very limited way with the problem of multiple myeloma (MM). The subject of the submitted paper was evaluation of the relationship of soluble forms of "vascular cell adhesive molecule-1" (sVCAM-1) and "intercellular cell adhesion molecule-1" (sICAM-1) in serum from the peripheral bloodstream (PBS) and serum from a bone marrow aspirate (BMA) with selected clinical and laboratory indicators of MM (beta 2-microglobulin, thymidine kinase, immunochemical type of MM, S-creatinine, S-monoclonal immunoglobulin, S-albumin, Hb, percentage ratio of plasmocytes in bone marrow, age, performance status, stage and substage of MM and activity of disease) and proliferation characteristics of myeloma plasmocytes. The authors analyzed two groups of patients with MM, a group of 64 examined in different stages of MM and a group of 39 examined when the diagnosis of MM was established (median age 63 and 64 years, male/female ratio 1.6 and 1.3:1). The sVCAM-1 and sICAM-1 levels were examined by the ELISA method. Elevated values of sVCAM-1 in PBS were recorded in both groups in 87.5% and 87% patients, medians of sVCAM-1 exceeded the upper range of normal values (714 ng/ml) almost twice (1180 and 1295 ng/ml) whereby median values in BMA (1347 and 1546 ng/ml) were always somewhat higher than in PBS. Elevated sICAM-1 values in PBS were found in 35 and 33% patients, median levels of sICAM-1 in PBS and in BMA did not exceed the upper normal range (691 ng/ml) and did not differ substantially (518 vs. 476 and 518 vs. 500 ng/ml). Correlation analysis (Pearson's correlation coefficient and Mann-Whitney's test, p0.05) revealed in both groups a significant relationship of both CAM assessed in PBS and BMA (sVCAM-1 p-0.0000 and p-0.012, sICAM-1 p-0.0000 and p-0.0011). No relationship was found between sVCAM-1 and s-ICAM-1 levels assessed in PBS and BMA with proliferation indexes of myeloma plasmocytes, i.e. values of the propidium-iodide index PI/CD38 and PI/B-B4 (CD138). In the whole group of 64 patients a relationship was found between sVCAM-1 in PBS and values of S-creatinine (p - 0.004), Hb (p - 0.033), S-albumin (p - 0.035), S-beta 2-microglobulin (S-B2M) (p - 0.0000) and S-thymidine kinase (S-TK)(p-0.0000), when evaluating BMA, a relationship with B2M (p -0.011). In the group of 39 patients examined when the diagnosis of MM was made a relationship was found of sVCAM-1 in PBS to S-B2M) (p - 0.0000), S-TK (p-0.0000) and to S-creatinine (p -0.005), in BMA there was only a relationship with B2M (p - 0.020). In the whole group of 64 patients there was no relationship between s-ICAM levels in PBS with any of the examined indicators, when evaluating BMA only a relationship with B2M (p - 0.038) and TK (p - 0.022). In the group of 39 patients examined during the diagnosis of MM a relationship was found of sICAM-1 only with B2M in BMA (p - 0.013). In the total group of 64 a relationship was found between sVCAM-1 in PBS with the patient's age (p - 0.032) and the substage of MM(p-0.024), in the group of 39 patients a relationship between sVCAM on PBS and the substage of MM (p -0.031). On analysis of sICAM-1 a relationship was found between levels in BMA only with the patient's age (p -0.015). From the investigation ensued that despite evidence of a number of correlations between sVCAM and sICAM-1 levels and clinical and laboratory indicators of MM no relationship was found which could be applied under conditions of clinical practice. Assessment of levels of different indicators in serum of bone marrow aspirate did not reveal any advantages over examination in peripheral blood serum.

Adult↗

PubMed1999

[Importance of determining the propidium-iodide index of plasmacytes in multiple myeloma. I. Relation to selected laboratory indicators of the disease].

In a group of 85 patients with multiple myeloma (MM) incl. 50 patients examined at the time when the diagnosis was established the relationship of the values of the propidium-iodide index (PI index) of myeloma plasmocytes of the patients were examined by flow cytometry using the double staining method, and selected laboratory parameters of the disease were analyzed. It was revealed that the values of the PI index examined with the aid of different "identification" monoclonal antibodies did not differ significantly. The median and average value of the PI index was in the whole group for PI/CD38 2.3 and 2.3%, for PI "UHKT" 1.8 and 1.8% and for PI/B-B4(CD138) 2.2 and 2.4%. In the group of patients examined at the time when the diagnosis of MM was established before chemotherapy the median and average value of the PI/CD38 index was 2.0 and 2.2%, PI/"UHKT" was 1.5 and 1.6%, PI/B-B4 (CD138) 2.6 and 2.5%. In the two analyzed groups no statistically significant correlations of PI/CD38,/"UHKT" and B-B4(CD138) index were found with the number of granulocytes, thrombocytes, immunochemical type and the value of the serum M-component, and levels of S-beta 2 microglobulin, S-urea, S-creatinine, S-calcium, and S-lactic dehydrogenase. A significant positive correlation was found in both groups with the level of S-thymidine kinase, in the whole group of indexes PI/CD38 and PI/B-B4(CD138) with the severity of anaemia, index PI/CD38 correlated with S-albumin and index PI/B-B4(CD138) with the percentage ratio of plasmocytes in bone marrow. It was revealed that examination of the propidium-iodide index is a suitable and prompt method for evaluation of proliferative properties of the myeloma population.

Adult↗

PubMed1999

[Importance of determining the propidium-iodide index of plasmacytes in multiple myeloma. II. Relation to disease extent and activity].

The authors evaluated in a group of 50 patients with multiple myeloma (MM), examined when the diagnosis was established before onset of treatment, and in a group of 85 patients examined in different stages of MM the relationship of proliferative characteristics of myeloma plasmocytes assessed by means of the propidium-iodide index PI/CD38, PI/"UHKT" and PI/B-B4(CD138) with the progression, "performance status" and the activity of the disease. With the exception of a different value of the PI/CD38 index between stages 1 and 3 evaluated according to Durie-Salmon, in the whole group of patients no relationship was found with the progress of the disease. When evaluating the whole group the authors observed a difference between sub-stages A and B (i.e. between patients without and with a serious impairment of renal function) when using indexes PI/CD38 and PI/B-B4(CD138). Only in the whole group of 85 patients the authors found a significant relationship of all proliferation indexes (PI/CD38PI/"UHKT" and PI/B-B4) with the "performance status" according to ECOG score to or > or = 3 vs. < 3. In both groups there was a very close statistically significant relationship without the activity of the disease whichever of the three proliferation indexes was used. It was revealed that patients with the active but stable form of the disease have different PI/CD38 and PI/B-B4(CD138) indexes within the framework of the same stage of MM (stages 1 + 2 vs. 3). From the investigation ensues that examination of the PI proliferation index, in particular PI/B-B4(CD138) or possibly PI/CD38 using multiparametric flow cytometry is a valuable method extending hitherto used examination procedures in MM, and that it replaces adequately former autoradiographic and microscopic immunofluorescent techniques.

Adult↗

PubMed1998

[Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group].

We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals.

Adolescent↗

PubMed1996

[Soluble interleukin-6 receptors in the serum in multiple myeloma].

BACKGROUND: Infrequent studies, having been published so far, have brought few, partly contradictory, results on the importance of soluble receptor of Interleukin-6 (sIL-6R) in serum in patients with multiple myeloma (MM). The aim of the study was to find out, if there are applicable relations between the levels of sIL-6R and the values of selected clinical and biochemical indices and the levels of some cytokines in serum. METHODS AND RESULTS: The authors analyzed a cohort of 50 patients suffering from MM (age median 64 years, range 34-83 years, ratio of men versus women 1.2:1.0). The soluble IL-6R and other cytokines were examined by ELISA assay, clinical stages of the disease were evaluated according to Durie-Salmon and Bataille. Increased values of sIL-6R (> 90 ng/ml) were in 28 (56%) of patients, median value was 87.4 (range 28.3-220 ng/l). Correlation analysis (Pearson test, p < 0.05) proved a statistically significant relation between the levels of sIL-6R and the values of beta 2-microglobulin (S-B2M) and thymidine kinase (S-TK) in serum. There was no relation to the erythrocyte sedimentation velocity, haemoglobin levels, calcium, urea, creatinine, lactate dehydrogenase, albumin, monoclonal immunoglobulin, C-reactive protein, ferritin, IL-1, IL-2, sIL-2R, IL-6, TNF-alfa, and the occurrence of myeloma plasmocytes in bone marrow. No differences were found between the patients with normal values of S-B2M (< 3 ng/ml) and plasmocytes in bone marrow (< 5%) in comparison with the groups of patients with increased values (3-6, > 6 ng/ml and > 20%, respectively). There was no statistically significant relation of the levels of sIL-6R to clinical stages of MM (1-3) and the degree of activity of the disease. CONCLUSIONS: Increased values of sIL-6R, detected in more than a half of the cohort, were, with the exception of S-B2M, S-TK and massive infiltration of bone marrow by myeloma plasmocytes, in no applicable relation to selected biochemical indices, to the level of some cytokines and to the degree of advancement and activity of the disease.

Adult↗

PubMed1996

[The bromodeoxyuridine index in multiple myeloma. I. Relation with selected laboratory indicators of the disease].

In a group of 70 patients with multiple myeloma (MM), formed by 25 patients examined while establishing the diagnosis and 45 patients examined in different stages of the disease, the authors evaluated the relationship of the bromodeoxyuridine "labelling index" (BrdUrd-LI) of myeloma plasma cells assessed by the method of double immunofluorescence (using antibody BU-1) and selected laboratory indicators of the disease. In the whole group the median and mean values of BrdUrd-LI of myeloma plasma cells were 2.0 (0.6-4.4%) and 2.1 +/- 0.9%, in the group of 25 patients examined during diagnosis it was 1.8 (0.6-4.1%) and 1.9 +/- 0.9%, in the group of 45 patients examined during different stages of MM it was 2.4 (0.6-4.4%) and 2.4 +/- 0.8%. Neither in the whole group nor in the sub-groups any statistically significant correlations were found between BrdUrd-LI values and the degree of anaemia, values of S-creatinine, S-MIG, S-albumin, S-B2M, S-ferritin, S-thymidine kinase, S-IL-6, S-IL-2, S-kIL-2R, the percentage ratio of myeloma plasma cells in bone marrow and the synthetic index of myeloma plasma cells paraprotein.

Adult↗

PubMed1996

[Determination of the bromodeoxyuridine index in multiple myeloma. II. Relation to level of advancement and disease activity].

In a group of 70 subjects with multiple myeloma (MM) formed by 25 patients examined before establishment of the diagnosis and 45 patients evaluated in different developmental stages of the disease, the authors evaluated the relationship between the value of the bromodeoxyuridine "labelling index" (BrdUrd-LI) and the clinical activity, stage and course of the disease. The authors revealed statistically significantly higher values of BrdUrd-LI in the group of patients in the "active" phase of the disease than in the "stable-plateau" phase of the disease. This applies also to findings within different clinical stages of the disease. The authors did not reveal any relationship of BrdUrd-LI values and the stage of progress of the disease evaluated by means of staging systems according to Durie-Salmon, the British Medical Research Council and Bataille. Patients in the "stationary-plateau" phase with a longer than five-year duration of the disease (61-211 months) had all low BrdUrd-LI values (median 1.4%), while subjects in the "late-preterminal" stage of MM with possible extramedullary spread and leukaemization of the process had in all instances higher values (3.2%). Evidence was provided that examination of the proliferating characteristics of myeloma plasmocytes by means of BrdUrd-LI contributes to a better evaluation of the severity, development and prognosis of the disease.

Bromodeoxyuridine↗

PubMed1995

[Serum interleukin-6 in multiple myeloma: I. Relation to selected laboratory indicators of disease].

In a group of 111 patients with multiple myeloma (MM) comprising a group of 34 patients examined when the diagnosis was established and a group of 77 patients evaluated in different stages of the disease, the author examined the relationship between the interleukin-6 serum level (IL-6), assessed by the method of enzyme immunoanalysis and selected laboratory indicators of the disease. Elevated IL-6 values were recorded in 38% of the patients. In neither of the groups significant relations were found between IL-6 and calcium, urea, creatinine levels, the amount and type of monoclonal immunoglobulin, lacticode dehydrogenase, beta 2-microglobulin, ferritin, IL-2 and its soluble receptor in serum and the incidence of myeloma plasmocytes in bone marrow. In the second (but not in the first) group a significant relationship was recorded between IL-6 levels and the red cell sedimentation rate, the Hb value, the CRP level and serum albumin and the value of thymidinekinase in serum of patients with a value beyond the normal range. From the investigation ensues that examination of IL-6 serum levels in MM contributes so far mainly to improvement of the diagnosis and expedient classification of this disease in clinical practice.

Adult↗

PubMed1995

[Serum interleukin-6 in multiple myeloma. II. Relation to activity and stage of disease].

In a group of 111 subjects with multiple myeloma (MM) comprising a group of 34 patients examined when the diagnosis was established and a group of 77 patients examined in different stages of development of MM the authors evaluated the relationship between interleukin-6 (IL-6) serum levels and the clinical activity and the stage of the disease. In both groups a significant relationship was found between IL-6 and the clinical activity of MM; "stable" and "active" stages of the disease differed by the frequency of elevated values and the level of IL-6. In both groups the authors recorded rising levels and a rising rate of subjects with elevated IL-6 levels with advancing stages of the disease. When staging systems were used according to Durie-Salmon, the British Medical Research Council and according to Bataille the highest IL-6 values were recorded in the third stage of the disease, these values being significantly higher than in stages 1 and 2. In the group assembled at the time of assessment of the diagnosis of MM the described differences did not reach (with the exception of the evaluation according to Bataille) statistical significance. The classification of patients in stages 1-3 into sub-groups with regard to the activity of the disease ("stable" and "active") was associated with significantly different IL-6 levels. The investigation revealed that examination of IL-6 levels contributes at present rather to the understanding of the pathogenesis and biology of MM than to practical evaluation of the severity, activity and stage of the disease.

Biomarkers, Tumor↗

PubMed1994

[Clinical importance of the paraprotein index in multiple myeloma].

In a group of 54 patients with multiple myeloma, hitherto not treated by chemotherapy, the paraprotein index was assessed. It was revealed that this simple and readily available indicator is related to the degree of anaemia, the serum beta-2-microglobulin value, the degree of bone marrow infiltration by myeloma plasmocytes and the survival period. The authors found no relation to age, albumin, urea, creatinine, serum calcium values and degree of skeletal affection. It was revealed that values of the paraprotein index declined with the advancing disease evaluated according to Durie-Salmon's system. It may be said that the paraprotein index can be considered in patients with multiple myeloma an indicator which contributes to more profound knowledge of individual biological characteristics of the myeloma population and the prognosis of the disease.

Female↗