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Myelomatous bone disease affects about 90% patients with multiple myeloma and solitary myeloma as well. In initial stage it is manifested as osteopenia with osteoporosis or osteolytic foci, pathologic fractures followed by neurologic complications. Ethiopathogenitically a role is played by cytokine interactions with local chemokines produced by myeloma cells and activated stromal and hemopoietic cells (osteoblasts, monocytes, macrophages) resp. From the TNF-alpha family glycoprotein complexes are liberated (RANK-L), which support activation and proliferation or are inhibitory (osteoprotegerins). Similarly in the family TGF-beta several izotypes of antiinflammatory cytokines are known (the most important is TGF-beta 1 and the morphogenetic protein-2), which have a fibrotizing effect in bones, because the produced osteoid is insufficiently mineralized. The effect is a pathologic remodelation of the skeleton. In the diagnosis of multiple myeloma the immunological knowledge is used in the initial diagnosis (immunophenotypization, follow up of TNF-alpha, TGF-beta 1, IL-1, IL-6 etc). Important are also biochemistry values of increased osteoresorption (changes of calcium, parathormone, excretion of collagen fission products, osteocalcin, the bone alkaline phosphatase). In the following part the authors inform about favourable results of long-term treatment with bisphosphonates (Bonefos, Ibandronate) in combination with anti-tumor chemotherapy in 364 patients. During a 15 years observation period median survival of 94 months with a 35% probability of 10 year survival was achieved with a significant decrease of bone complications in 58% compared to 14% in the placebo group.

Purpose: To evaluate the impact of an additive therapy with an oral enzyme (OE) preparation given for more than 6 months additionally to standard combination chemotherapy (vincristine/melphalan/cyclophosphamide/prednisone (VMCP)- or methylprednisolone/ vincristine/CCNU/cyclophosphamide/melphalan (MOCCA)-regimen) in the primary treatment of patients with multiple myeloma stages I-III., Methods: A cohort of 265 patients with multiple myeloma stages I-III was consecutively treated at our institution in two parallel groups (control group (n = 99): chemotherapy +/-OE for less than 6 months; OE-group (n = 166): chemotherapy + OE for more than 6 months). The median follow-up time in the stages I, II, and III for the OE-group was 61, 37, and 46.5 months, respectively; for the control group the respective values were 33, 51.5, and 31.5 months. The primary endpoint of the study was disease-specific survival. Secondary endpoints were response to therapy, duration of first response and side effects. The chosen method for evaluation was the technique of a retrolective cohort analysis with a concurrent control group. Survival analysis was performed by the Kaplan-Meier method and multivariate analysis was done with the Cox proportional hazards model., Results: Significantly higher overall response rates and longer duration of remissions were observed in the OE-group. Primary responders showed a longer mean survival time than non-responders. Additive therapy with OE given for more than 6 months decreased the hazard of death for patients at all stages of disease by approximately 60%. Observation time was not long enough to estimate the median survival for patients at stages I and II; for stage III patients it was 47 months in the control group versus 83 months for the patients treated with OE (P = 0.0014) which means a 3-year gain of survival time. Significant prognostic factors for survival, in the Cox regression analysis, were stage of disease and therapy with OE. The OE-therapy was generally well tolerated (3.6% of patients with mild to moderate gastrointestinal symptoms)., Conclusion: OEs represent a promising new additive therapy in multiple myeloma which will be further evaluated in a randomized phase III trial in the USA.

The problem of osteoporosis is world-wide in people above 50 years of age. As this period is also a risk period for the development of multiple myeloma or other malignant processes, comprehensive differential diagnosis of malignant and benign osteoporosis is essential. By retrospective analysis of a 12-year group of 270 patients treated by chemotherapy on account of multiple myeloma the authors selected a group of 151 patients treated in addition to chemotherapy and immunomodulating drugs (mixture of proteolytic enzymes-Wobe Mugos) for 2-3 years, also with biphosphonates. At the time ofdiagnosis osteoporosis was in 24.5% patients the only finding on bones. When biphosphonates (Bonefos, Ibandronate) and chemotherapy were administered during a three-year observation period the bone process was stable in 61.59%, osseous changes disappeared in 11.26% and progression of osteolysis was recorded in 27.15%. The objective of the work was to emphasize the importance of a correct diagnosis of osseous changes which can progress even in clinically asymptomatic myelomas.

Background: The most frequent complications of oral administration of medicinal iron are gastrointestinal complaints the incidence of which correlates with the iron content of the preparation. The objective of the present work was to compare the effectiveness and tolerance of two ferrous sulphate preparations, Aktiferrin capsules and Tardyferon dragées which differ as to the elemental iron content., Methods and Results: To two groups of patients with sideropenic anaemia selected at random (39 women and 1 men, age 14-61 years, median 28 years) Aktiferrin or Tardyferon was administered. Administration of the preparations which have a more than double different elemental iron content had a comparable effect on the investigated haematological parameters. In the group treated with Akiferrin no GIT intolerance was observed, in the group with Tardyferon it was observed in four patients., Conclusions: Aktiferrin has a comparable therapeutic effect although it contains 2.5 times less elemental iron, as compared with Tardyferon.

The authors present the results of 23-year protocol studies of survival with multiple myeloma, focused on problems of perspective long-term survival. Of 535 diagnosed patients between 1970 and 1990 the authors checked regularly and treated 475. In addition to 60 latent forms where treatment was administered only when clinical symptoms developed or after progression of laboratory signs, to all patients treatment was administered according to protocols (monotherapy-cyclophosphamide prednisone in 1970-1975 only to 30 patients, the remainder had combined treatment--COPP, VMCP, MOCCA); in the third stage of the disease MOCCA treatment is better. The median of survival of patients after VMCP treatment (in stage II) MOCCA (in stage III) is more than 90 months, 15% survive for more than 10 years. The authors emphasize the importance of combined intensive treatment of patients for the prognosis of survival. Long-term experience revealed that patients achieve an objective response in 85%, while the risk of leukaemic and cancerogenic complications is low (1.1%). The therapeutic effect and survival period are favourably affected by immunomodulation treatment (Interferon, proteolytic enzymes, thymus factor).

At present attention is focused on research of biomodulating influences on tumorous processes, in particular inhibition of metastatic spread of tumors. In the aetiopathogenesis an important part is played by immune complexes, interaction of cytokines. The authors tested the supporting effect of hydrolytic enzymes in plasmocytoma and immunocytoma. The enzymes were administered along with cytostatic preparations according to the MOCCA pattern. They recorded a more rapid onset and longer persistence of remissions, a marked decline of total proteins, paraproteins, beta-2-microglobulin. Complications associated with paraprotein (hyperviscosity syndrome, nephrotic syndrome, peripheral angiopathy) improved. A combination of chemotherapy and enzymatic treatment proved effective and suitable, in particular for patients with interferon intolerance.

The authors discuss the prognostic impact of immunophenotyping of circulating lymphoplasmatic cells in the peripheral blood stream in patients with generalized plasmocytoma. From a group of 250 patients followed up from 1981 to 1991 they selected a sub-group of 70 patients where they evaluated in 1986-1991 after six-month intervals the phenotype of medullary and circulating cells. They used the method of immunofluorescent detection of the presence of cytoplasmic Ig, the kappa-lambda index and phenotyping of antigens CD 9, CD 10, CD 20, CD 38, HLA-DR by monoclonal antibodies. In a longitudinal investigation of the survival period they revealed that the finding of circulating cells with signs of non-differentiation (presence of antigen CD 10 detected by antibody CALLA, presence of antigens B 1 (CD 20), CD 9 on circulating lymphocytes) has a prognostic meaning suggesting shorter survival. There was a direct correlation between the increase of CALLA positive cells and CD 9 positive cells. The authors found also that release of the clonus with signs of immaturity was present when the disease developed into the aggressive stage. While the group of 250 patients had according to statistical analyses, when treated according to protocol VMCP/MOCCA, a median survival of 90 months, the median survival of the aggressive stage (with the plasmoblast and lymphoplasmocytic type resp.) was only 12 months. The authors emphasize the prognostic importance of immunological typing of heterogeneous plasmocytoma populations.

In respect to literary data, we tried to evaluate some qualitative and quantitative indices for prognosis of chronic lymphocytic leukemia (CLL). In the group of 117 patients we evaluated prognostic parameter proposed by Jaksic and Vitale, which takes into consideration so-called total tumour mass (TTM). In the group of patients investigated we did not succeed in confirmation of prognostic value of TTM scoring as determined at the time of CLL diagnosis. However, investigation of doubling time of total tumour mass (DT TTM) appeared to be more important. To determine reliable prognostic criteria for CLL, however, complex cooperative study on the greater group of patients is necessary.