[Richter's syndrome (bimorphologic malignant lymphoma)]. / Richterov syndróm (bimorfný malígny lymfóm).

Two distinct morphological types of malignant lymphoma in the same patient occur mostly due to transformation of a low grade lymphoma (CLL) into a large--cell non-Hodgkin lymphoma (high-grade lymphoma). Later reports have brough evidence of a clonal relationship between CLL and supervening NHL. The Richter's syndrome was found to be more frequent in patients with CLL displaying either multiple chromosomal aberrations or monoclonal gammapaties. In the last two decades reports have evidenced the existence of two types of the Richter's syndrome: one, the "classical" as a terminal event in a long evolving CLL, the other "variant" as the first clinical manifestation of a previously unrecognized subclinical CLL. Aggressive chemotherapy of CLL play a role in transformation of CLL to Richter's syndrome.

Oral therapy with proteolytic enzymes decreases excessive TGF-beta levels in human blood.

UNLABELLED: Therapy with oral proteolytic enzymes (OET) with combination drug products containing papain, bromelain, trypsin, and chymotrypsin has been shown to be beneficial in clinical settings such as radiotherapy-induced fibrosis, bleomycin pneumotoxicity and immunosuppression in cancer, all of which are nowadays known to be accompanied by excessive transforming growth factor-beta (TGF-beta) production. It has been demonstrated that proteolytic enzymes reduce TGF-beta levels in serum by converting the protease inhibitor alpha2 macroglobulin (alpha2M) from the "slow" form into the "fast" form, whereby the "fast" form binds and inactivates TGF-beta irreversibly. In this study we have investigated the effect of OET on the concentration of TGF-beta1 in serum of patients with rheumatoid arthritis (RA) (n = 38), osteomyelofibrosis (OMF) (n = 7) and herpes zoster (HZ) (n = 7). Seventy-eight healthy volunteers served as controls. TGF-beta1 levels in serum were assessed by enzyme-linked immunosorbent assay (ELISA). We have demonstrated that in healthy volunteers and in patients there exists a correlation between active and latent TGF-beta1 in serum (r=0.8021; P<0.0001). Treatment with OET had no significant effect on TGF-beta1 concentration in healthy volunteers or patients with a normal level of TGF-beta1. In patients with elevated TGF-beta1 concentration (> 50 ng/ml serum), OET reduced TGF-beta1 in RA (P < 0.005), in OMF (P < 0.05) and in HZ (P < 0.05). CONCLUSION: These results support the concept that OET is beneficial in diseases characterized in part by TGF-beta1 overproduction.

Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma.

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.

[Selection of donor-recipient pairs in families for allogenic bone marrow transplantation]. / Výber párov darca-príjemca v rodinách pre alogénnu transplantáciu kostnej drene.

In the years 1985-1999 452 were families investigated with the aim to find up an HLA-identical sibling for a patient suffering from a disease, the treatment of which requires bone marrow transplantation. Total number of investigated siblings (including patients) was 1334. HLA typing was done by serological methods, mixed lymphocyte culture test (MLC), and in the last three years also by DNA-typing (PCR-SSP). 188 HLA identical donor-recipient sib-pairs were found. At the same time the number shows that a potential donor could be found in 41.5% of investigated families.

[Frequency of HLA-A, HLA-B and HLA-Cw antigens in the Slovak population]. / Frekvencia antigénov HLA-A, -B, -Cw v Slovenskej populácii.

Results on HLA-A, -B and -Cw antigen frequencies in the Slovak population are presented. HLA-A, -B, -Cw antigens were determined in 654 healthy unrelated individuals. The highest frequency was observed for the antigens HLA-A2, -A1; HLA-B12, -B35, and HLA-Cw8. The least frequent antigens were HLA-A34, -A36, HLA-B58, -B67, -B70, -B77, and HLA-Cw8. The results were compared with those of the previous study and with those of Czech, Austrian and Hungarian populations. No statistically significant differences were observed. (Tab. 5, Fig. 2, Ref. 9.)

Allogeneic BMT for haematological disorders: single centre experience of University Hospital Bratislava.

Data on 65 sibling bone marrow transplantations (BMT) for various hematological disorders are reported. 51 patients had leukemia, 8 severe aplastic anemia, 4 myelodysplastic syndrome, one suffered from non-Hodgkin lymphoma and one from myeloid metaplasia. All but two patients have engrafted. Overall, 43 (66%) of 65 patients were alive 0,03-7,2 years (median not reached) as of June 23, 1997. Median time of observation was 13 months. Outcome of standard risk patients was significantly better than that of high risk patients (p=0,006). Our data confirm, that sibling BMT is an effective treatment modality with acceptable toxicity for younger patients with an early stage of serious hematological disorders.

[Density of adhesive proteins after oral administration of proteolytic enzymes in multiple myeloma]. / Sledovanie denzity adhezívnych proteínov po perorálnom podaní proteolytických enzýmov pri mnohopocetnom myelóme.

The authors present information on the presence of adhesive proteins on membranes of myeloma and precursor cells isolated from bone marrow and blood from a group of 33 patients examined by fluorescent flow cytometry. They also compare the density of integrins (CD29, CD49e, CD41, CD51 and CD61) and adhesive proteins from the group of "homing" receptors (CD44) and IgG "superfamily" (LFA-1, LFA-3, ICAM-1, N-CAM) and their changes after a single oral dose of a mixture of proteolytic enzymes (Wobe Mugos, Wobenzym, MUCOS Pharma, FRG). The authors observed a significant drop of CD29, CD54 (ICAM-1), CD58 (LFA-3) after Wobe Mugos, CD49, CD51, CD58 after Wobenzyme. The insignificant decline of density of CD44 on cells, as well as of the soluble receptor of CD44 after oral administration of proteolytic enzymes in serum, incl. the mentioned changes of integrins and other adhesive proteins, indicate the importance of enzyme preparations in the supporting treatment of malignant processes.

Myeloid activation antigen CD66/67: immunochemical and immunocytometric characterization with the Vth workshop monoclonal antibodies.

Flow cytometric and immunochemical studies performed with the CD66/67 panel antibodies from the Vth International Workshop on Leukocyte Antigens allowed to subdivide these antibodies into five groups, according to the molecular weights of polypeptides recognized by these antibodies on pooled healthy donor granulocytes. Although some monoclonal antibodies recognized either 95-110 kDa, or 160-180 kDa polypeptides, majority of the examined antibodies reacted with epitopes shared by both 95-110 kDa and 160-180 kDa polypeptides. Differential TPA-induced modulation of recognized antigens was observed with HL-60 and U-937 leukemia/lymphoma cell lines.

Prognostic value of plasma-cell immunophenotype in patients with multiple myeloma.

A review is given of the prognostic significance of immunophenotyping of blood lymphoplasmocytic cells. From a group of 250 patients followed from 1981 through 1991 a subgroup of 70 patients (followed 1986 through 1991) were phenotyped at 6-month intervals by immunofluorescence tests with monoclonal antibodies for cytoplasmic immunoglobulin, kappa-lambda index, CD71, CD10, CD20, CD38, and HLA-DR receptors. In course of a longitudinal study it was found that prognostic significance for shortened survival can be derived from the presence of circulating CD10, CD71, and CD20 positive undifferentiated cells in peripheral blood. There was a correlation between increase of CALLA positive and CD71 positive cells. Further, an increase of undifferentiated clone occurred during transition of the disease to an aggressive phase. The median survival of the total group of 250 patients treated by the VMCP/MOCCA protocol, according to statistical analysis, was 90 months, the median survival of the aggressive stage with plasmoblastic and lymphoplasmocytic cell type, respectively, was only 12 months. The significance of phenotypization in the prognostic evaluation of variant heterogenous myeloma types is stressed.

[The favorable effect of hydrolytic enzymes in the treatment of immunocytomas and plasmacytomas]. / Podporný úcinok hydrolytickych enzýmov pri liecbe imunocytómu a plazmocytómu.

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.

[Immunotyping of medullary and circulatory cells for prognostic evaluation of plasmacytoma]. / Imunotypizácia drenových a cirkulujúcich buniek pri prognostickom posúdení plazmocytómu.

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.