Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with B-cell chronic lymphocytic leukemia in the Polish population.

Abnormal expression of the costimulatory molecules cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28, and inducible co-stimulator (ICOS) leads to disturbances of immune response and an increased risk of cancer. An extended study was undertaken to evaluate the association among the polymorphisms CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CD28c.17+3T>C, and ICOSc.1554+4GT(8_15) and susceptibility to B-cell chronic lymphocytic leukemia (B-CLL) in the Polish population. The study revealed increased frequency of the CTLA-4g.319C>T [T] allele and the CTLA-4g.319C>T [T] phenotype in B-CLL patients compared with healthy controls (p = 0.003, odds ratio [OR] = 1.73; and p = 0.009, OR = 1.74, respectively). The presence of the CD28c.17+3T>C [C] allele and the CD28c.17+3T>C [C] phenotype increased the OR of B-CLL to 1.59 (p = 0.007) and 1.74 (p = 0.007), respectively. Either CTLA-4g.319C>T or CD28c.17+3T>C was associated with time to Rai stage progression. The distributions of the alleles and genotypes of the ICOS gene significantly differed between patients and controls (p = 0.0009 and p = 0.006, respectively). Individuals possessing short alleles were 2.02 times more prone to B-CLL than others (p = 0.001), whereas carriers of long alleles were protected from B-CLL (p = 0.02, OR = 0.62). The haplotype association study and multivariate analysis confirmed the association of CTLA-4g.319C>T and ICOSc.1554+4GT(8_15) gene polymorphisms with B-CLL. The polymorphic sites CTLA-4c.49A>G and CTLA-4g.*642AT(8_33) did not correlate with B-CLL. Our results are the first in the literature to report that gene polymorphism of the costimulatory molecules CTLA-4, CD28, and ICOS contributes to susceptibility to B-CLL.

[Coincidence of multiple myeloma and renal clear cell adenocarcinoma]. / Wspólistnienie szpiczaka plazmocytowego i raka jasnokomórkowego nerki.

There are only casuistic reports about the coincidence of renal carcinoma and lymphoproliferative diseases. We report a case of 59-year old patient who simultaneously developed renal clear cell carcinoma and IgG kappa multiple myeloma. After nephrectomy the progression of multiple myeloma was observed. The renal failure occurred and, as a consequence, the introduction of full doses of chemotherapy for multiple myeloma was unable.

[Serum soluble tumor necrosis factor alpha receptor (s-TNF-alpha R) and acute phase proteins as factors of a disease activity (and also as prognostic factors?) in patients with malignant lymphomas]. / Rozpuszczalny receptor dla czynnika martwicy nowotworów alfa(sTNF-alfaR) i bialka ostrej fazy jako mierniki aktywnosci choroby (czy takze--wskazniki prognostyczne?) u pacjentów z chloniakami zlosliwymi.

It was found that in neoplastic disorders levels of sTNF-alpha R and acute phase proteins are elevated and correlate with disease activity and poor prognosis. The aim of the study was to determine levels of sTNF-alpha R and acute phase proteins in patients with lymphoma at presentation and after treatment and compare with healthy individuals. Serum concentration of sTNF-alpha R was estimated by ELISA method, fibrinogen and haptoglobin by nephelometric method in 46 lymphoma patients and in 14 healthy individuals. Mean sTNF-alpha R concentration in lymphoma group was statistically significantly higher than in healthy individuals (p = 0.00057) and in patients with complete remission (CR) (p = 0.024). Mean concentration of fibrinogen and haptoglobin was significantly statistically higher at presentation of lymphoma than in CR (p = 0.0001, p = 0.0001). We found the correlation between the mean concentration of sTNF-alpha R, fibrinogen and haptoglobin at presentation of lymphoma. There was no difference in the survival time in patients with higher concentration of sTNF-alpha R. Our data indicate the important role of the elevated concentration of sTNF-alpha R, fibrinogen and haptoglobin as factors of disease activity in lymphoma patients but they do not correlate with disease's prognosis.

[Observation of D-dimer levels in serum of patients with acute leukemia]. / Obserwacja stezenia D-dimerów w surowicy u pacjentów chorych na ostre bialaczki.

The blood coagulation and fibrinolysis disorders are common complications observed in patients with acute leukemias, particularly in acute myelogenous leukemia. These abnormalities are mediated by thromboplastic substances released from the blast cells and the alteration of hemostatic properties of vascular endothelium. The plasma concentration of D-dimer (cross-linked fibrin degradation products), measured by enzyme immunoassay, using monoclonal antibodies, serves as a specific marker of the coagulation activation and fibrinolysis system. In our study, the plasma concentration of D-dimer was investigated in 142 patients with acute leukemia during clinical course--at the time of initial diagnosis, complete remission, relapse or in cases resistant to chemotherapy. It has been revealed that, at the time of initial diagnosis, the plasma level of D-dimer was elevated in most patients, irrespective of the type of acute leukemia. However, the initially elevated plasma concentration of D-dimer was significantly lower when complete remission had been achieved. Furthermore, in the majority of cases of relapse or resistance to chemotherapy, a further increase of plasma concentration of D-dimer is commonly observed.

Disseminated nocardiosis as a complication of Evans' syndrome.

Nocardiosis is an opportunistic infection caused by gram-positive, weakly acid-fast filamentous aerobic organisms. Three species cause infection in man: N. asteroides, N. brasiliensis, and N. caviae, the first one being the most common. With increased use of immunosuppressive therapy for various autoimmune diseases, opportunistic infection by Nocardia has increasingly been reported. N. asteroides infections manifest in various ways; the lungs, skin, and brain are the organs most frequently involved. We describe a patient with Evans' syndrome, a disease requiring long-term immunosuppression, who acquired systemic nocardiosis. The infection was primarily pulmonary, misdiagnosed as tuberculosis, with subsequent hematogenous dissemination to the skin and central nervous system. The diagnosis of cerebral involvement was difficult to prove, as the patient presented with stroke-like episodes. After a positive blood culture was obtained, antibiotic therapy was introduced. The patient's condition deteriorated and the brain with infiltration of the meninges, lungs, skin, and kidneys. Nocardia is an important but often overlooked opportunistic infectious agent in immunocompromised hosts, causing diagnostic and therapeutic problems. As the mortality of cerebral nocardiosis is greater than 80%, early diagnosis and appropriate therapy are crucial.

[Diagnostic difficulties in Gaucher disease: report of two cases]. / Trudnosci w rozpoznawaniu choroby Gauchera: opis dwóch przypadków.

Diagnostic difficulties of Gaucher disease, a disorder resulted from a deficient activity of glucocerebrosidase is reported. Gaucher disease was described in the 16 year old male, 5 years after manifestation of the very first symptoms (fracture and osteomyelitis). At the age of 14, the cirrhosis due to viral hepatitis accompanied with splenomegaly was diagnosed. This findings was not associated with the earlier osseous disorders. Histopathologic examination of the removed spleen facilitate the diagnosis. The second case refers to 20 year old female. Clinical symptoms and additional test pointed to malignant neoplasm of thyroid, the reproductive organs or cancer of indistinguishable primary focus with metastases in the liver. Trepanobiopsy of bone marrow had made an accurate diagnosis possible, while determination of beta-glucosidase activity in peripheral white blood cells, chitotriosidase activity, and molecular investigations of gene specific to beta-glucocerebrosidase proved it.

[Evaluation of phenazone oxidation and sulfadimidine acetylation in patients with hematologic neoplasms]. / Ocena procesów utleniania fenazonu i acetylacji sulfadimidyny u chorych na nowotwory krwi.

The aim of our study was to estimate of phenazone oxidation and sulfadimidine acetylation in patients with Hodgkins disease, non Hodgkins lymphoma and acute leukemia. We observed increase in liver microsomal enzyme activity and predominance of the rapid acetylator phenotype in these pathological states. It should be taken into account when dosing drugs which are metabolized as markers of the liver metabolic efficiency like phenazone and sulphadimidine. One can also expect these patients to have a genetic predisposition to the development of cancer disease.

[Preliminary results of conservative combination radiotherapy and chemotherapy in early stages of Hodgkin's disease]. / Wstepne wyniki oszczednej, kombinowanej radioterapii i chemioterapii wczesnych stadiów choroby Hodgkina.

20 patients in early stages (I-IIB) Hodgkin's disease were treated with smaller than commonly used doses of cytostatics and radiation. Men were given EBVD-CVPP-EBVD (epirubicin, bleomycin, vinblastine, DTIC, cyclophosphamide, vinblastine, procarbazine, prednisone) and women: CVPP-EBVD-CVPP. Radiotherapy was limited to involved and adjacent fields. In all patients complete remission was achieved lasting now 9 to 107 months (mean 55 months). Two patients relapsed. No undesirable early side effects were observed. Further observations will show if such therapeutic option in non-advanced Hodgkin's disease is sufficient.

[Circulating immune complexes as markers of Hodgkin's disease activity]. / Krazace kompleksy immunologiczne jako wyznaczniki aktywnosci ziarnicy zlosliwej.

Immune complexes may appear in autoimmune, lympho- and meyloproliferative diseases and in solid tumors. Literature data are presented on immune complexes in Hodgkin disease taking into account their prognostic importance in the course of the disease.

[Diagnostic difficulties with a tumor in deep tissues of the buttock]. / Trudnosci diagnostyczne guza glebokich tkanek posladka.

Diagnostic difficulties in a case of a large tumor localized in the deep tissue of buttock in a 29-year old woman is described. The patient was very severely ill presenting with neurological symptoms and immobilization of the left coxal joint, what strongly suggested a neoplasm and this was supported by the CT scan. USG examination allowed diagnosis of a deep hematogenic staphylococcal abscess of the buttock, probably due to extensive oral sepsis and staphylococcal septicaemia. Systemic antibiotic therapy as well as evacuation of pus caused a complete recovery of the patient.

[Results of alternating treatment of multiple myeloma--cytostatics VBMCP and recombinant interferon alfa-2B]. / Wyniki naprzemiennego leczenia szpiczaka mnogiego--cytostatykami VBMCP i rekombinowanym interferonem alfa-2B.

In 19 patients with recently diagnosed multiple myeloma 3-week cycles of vincristine, BCNU, melphalan, cyclophosphamide and prednisone alternating with interferon were administered over 6-12 months. Results were compared with a control group of 33 myeloma patients treated exclusively with VBMCP cytostatics. In interferon treated patients objective response was more frequent (76%) and median survival time longer (above 35 months).

[Results of the treatment of non-Hodgkin's lymphoma with 6 cytostatic drug combination]. / Wyniki leczenia chloniaka nieziarniczego 6-lekowym zestawem cytostatyków.

In 20 patients with non-Hodgkin lymphoma as the first treatment and in 10 patients with the same diagnosis as the second treatment (group II) has been applied the therapeutical protocol proposed by I. Koza et al., composed of 4 monthly cycles of cyclophosphamide, vincristine, bleomycin, methotrexate and prednisone and in the other 4 cycles of doxorubicin, vincristine bleomycin, prednisone. The diagnosis in the I group was: immunoblastic lymphoma in 13 cases, other high grade lymphomas in 5 and low grade lymphoma in 2 cases. In the group II half of the patients showed low or intermediate grade lymphoma but with maximal clinical advancement and resistance to previous therapy. Complete remission (CR) has been obtained in 12 patients of the I group, partial remission (PR) in 7, 1 patient did not respond to therapy. In 3 cases relapse of the disease has been noted, including 2 patients in whom relapse occurred before finishing therapy: the patients remained resistant to alternative one. In the group II the PR and CR has been obtained in 5 and 3 cases respectively: 2 patients with immunoblastic lymphoma resistant to previous therapy did not respond either. Among undesirable effects myelosuppression, mainly granulocytopenia has been mostly noted: infection and septic shock was a cause of death in 1 patient. In 2 patients severe polyneuropathy and in 2 other mucositis of the digestive tract was noted. The treatment used gives beneficial results as induction therapy in cases of immunoblastic lymphoma and enables obtaining remission in therapy resistant cases of low grade lymphoma.