Small cell lung cancer is not associated with the presence of anti-fucosyl-GM1 ganglioside autoantibodies reactive in immunoenzymatic test.

The characteristic feature of small cell lung cancer carcinoma (SCLC) is the aberrant expression and abundant presentation of fucosyl-GM1 ganglioside (FucGM1). In the present study we searched for the presence of anti-FucGM1 ganglioside, as well as anti-GM1, GM2 and GD3 ganglioside autoantibodies in the sera of patients with SCLC and as a control, in sera of patients with renal cell cancer (RC) and healthy blood donors. The autoantibodies against FucGM1 were present at low titer in only three of 36 SCLC patients, and with similar titer in two of 36 RC patients and four of 36 healthy controls. Likewise, the autoantibodies against GM2 and GM3 gangliosides were found only sporadically and with the same titer and frequency in cancer patients as in healthy persons. Anti-GD3 autoantibodies could not be detected in any of the screened sera.

[Hepatic tuberculosis]. / Gruzlica watroby.

Tuberculosis of the liver can be the only manifestation of the disease or it may be a part of disseminated process. Three cases of liver tuberculosis were presented. In one of them the process was restricted to the liver and the diagnosis was made only at autopsy. In two other cases, tuberculosis of the liver was a part of disseminated process. In one of them the impairment of liver function improved after therapy and in another one, in spite of therapy, the patient died with signs of cardio-respiratory and hepatic insufficiency.

[Churg-Strauss syndrome does not respond to immunosuppressive treatment]. / Zespól Churg-Straussa nie reagujacy na leczenie immunosupresyjne.

A case of 35-years old woman with Churg-Strauss syndrome was presented. The appropriate diagnosis was established on the typical clinical history and microscopic studies. Clinical observation revealed a short-term improvement after immunosuppressive therapy.

[Chemotherapy versus chemoradiotherapy in patients with limited small cell lung carcinoma]. / Chemioterapia versus naprzemienna chemio-radioterapia u chorych z ograniczona postacia drobnokomórkowego raka pluca.

62 patients with a limited small cell lung cancer were randomly qualified into two groups. 32 patients of the first group were treated only with the chemotherapy regimen, consisted of three drugs (Carboplatine, Etoposide and Vincristine administered in 6 courses, on regular, 3-weeks basis). The second group of 30 patients had been treated with the identical chemotherapy schedule, but alternatively combined with a primary site irradiation in a total dose of 40Gy, applied in parts after the chemotherapy courses 2, 3, and 4. The significantly higher proportion of a complete remission results was observed in the alternate-treatment group: 14/30 (46.7%), compared with the chemotherapy-only group: 10/32 (31%). Alternate chemoradiotherapy resulted both in the increased median remission duration time, and the increased median survival time. Only in the alternate chemotherapy group, in 14/30 patients (46.7%) the pneumotoxicity symptoms appeared, whilst no differences in other organ-specific treatment-induced toxic effects were noted.

[Cytostatic treatment of patients with advanced non-small cell lung cancer]. / Leczenie cytoredukcyjne chorych na zaawansowanego niedrobnokomórkowego raka pluca.

92 patients with advanced non-small cell lung cancer were treated with cisplatin 80 mg/m2 day 1 and etoposide 120 mg/m2 on days 1-3. In 58 of them vinblastine 5 mg/m2 was also applied on days 1 and 3. In 25% of all cases partial response and in another 26% minimal regression was found after 2 courses of chemotherapy, independently to treatment modality. Partial regression was observed significantly more often in patients with adenocarcinoma, but survival time was significantly shorter in this group. Median survival time was 8 months for all patients, 10 months for stage IIIB and 6 months for stage IV. This difference was significant.

[The use of monoclonal antibodies in the detection of small cell lung cancer metastases in bone marrow]. / Próba zastosowania przeciwcial monoklonalnych do wykrywania przerzutów drobnokomórkowego raka pluca w szpiku.

Expression of a number of antigens associated with small cell lung cancer (SCLC) have been proposed as a marker of malignancy and the diagnostic tool for the staging procedures and important prognostic factor. Since the bone marrow (BM) was described as a frequent site for SCLC metastases, we have decided to assess clinical importance of cancer cells detection in BM, using immunofluorescence with MAC-1, MAC-31, NSE and anti-Fucosyl-GM1 (PF3) antibodies. The group of 32 patients with SCLC was assessed using our panel of antibodies. Control group consisted of 5 patients with other malignancies (3 patients with malignant lymphoma, 1 with chronic lymphocytic leukaemia and 1 with non-SCLC). The study revealed no correlation between the expression of SCLC markers in patients BM and the cancer treatment outcome measured as a response for treatment, time to progression, and survival time, and no significant difference was found between the patients and control group.

[Usefulness of CD1 expression on surfaces of cells in bronchoalveolar fluid for diagnosis of histiocytosis X--our experience]. / Wykorzystanie oznaczania ekspresji CD1 na powierzchni komórek z popluczyn pecherzykowo-oskrzelowych do rozpoznawania histiocytozy X-wlasne doswiadczenia.

Histiocytosis X (HX), also referred as Langerhans cell granulomatosis is a disorder characterized by the presence of destructive granulomas containing Langerhans cells, lymphocytes, eosinophils and fibroblastes in the involved organs. Three presentations are commonly observed: 1) nonproductive cough or effort dyspnea, 2) spontaneous pneumothorax 3) incidental pulmonary infiltrates on chest X-ray in asymptomatic patients. HRCT may be helpful in the initial diagnosis of pulmonary HX. HRCT scans show nodules, cysts and estimate the extent of disease. But the final diagnosis of histiocytosis X requires the histologic demonstration of specific histiocytosis X cell in biopsy specimens of the lung. The aim of this study was to define the importance of the detection of Langerhans cells in bronchoalveolar lavage fluid (BALF) for the diagnosis of HX. The searched cells express a specific CD1 antigen, recognized by the monoclonal antibody OKT-6. In our study the demonstration of more than 5% of CD1 positive cells was defined to confirm HX. We have studied the BALF in 21 patients with suspected histiocytosis X. In BALF of 4 patients more than 5% of CD1 positive cells were found. In 1 of them HX was confirmed with open lung biopsy. Two patients displayed 5% of CD1 positive cells. The final diagnosis of the first patient was hypersensitivity pneumonitis and of the second one was bronchitis chronica. In 5 patients out of 15 patients in whom less than 5% of CD1 positive cells were found histiocytosis X was histologically proven. In other 10 patients the following disorders were histologically recognised: pulmonary emphysema 3 cases, pneumoconiosis-3, LMA-BOOP-1, sarcoidosis-1 and pleuritis eosinophilica-1. The estimation of Langerhans cells in BALF can be a useful method among the diagnostic procedures for histiocytosis X. It is necessary to remember that demonstration of less than 5% of CD1 positive cells do not exclude histiocytosis X.

Decreased antibody-dependent cellular cytotoxicity in various types of leukaemia in man.

Antibody-dependent cellular cytotoxicity (ADCC) by cells from peripheral blood was studied in patients with; chronic lymphocytic leukaemia (CLL), chronic granulocytic leukaemia (CGL), acute lymphoblastic leukaemia (ALL), acute non-lymphoid leukaemia (ANLL) and compared with that of healthy donors. The ADCC activity in all the types of leukaemia was on the average lower as compared with the control values, being especially low in both CLL and CGL. Further, it has also been shown that the ADCC activity of non-leukaemic blood cells in ANLL was lower as compared with control values. The latter observation indicates that, at least in ANLL, the reduced ADCC potential of peripheral blood cells is not due to dilution of effector cells by poorly- or non-active leukaemic cells.

Possible mechanism of selective killing of myeloid leukemic blast cells by lymphokine-activated killer cells.

Major histocompatibility complex-unrestricted lymphokine-activated killer (LAK) cells have been proposed as therapy for a variety of hematologic malignancies. Because these cells recognize and kill their targets independently of their antigen specific CD3 receptor, it is unclear how they might discriminate between normal and malignant cells. We now propose one such mechanism for the selective killing of myeloid leukemia blasts. While both CD2+ and CD2- activated killer cells may inhibit the clonogenic growth of myeloid leukemia cells, only the CD2+ subset effectively inhibits the growth of normal myeloid (granulocyte-macrophage and granulocyte) progenitors. This difference appears to reflect differential requirements for cell adhesion molecule recognition between normal and malignant progenitor cells. Inhibition of the growth of normal granulocyte-macrophage colonies by CD2+ LAK cells is blocked by antibodies to the CD2-lymphocyte function-associated antigen 3 (LFA-3) (CD58) cell adhesion system. In contrast, these antibodies have no effect on CD2+ LAK-mediated inhibition of malignant cell clonogenic growth. Instead, antibodies to the LFA-1 (CD11a/CD18)-intercellular adhesion molecule 1 (ICAM-1) (CD54) adhesion system reduce inhibition. These differences correspond to differential expression of the CD54 cell adhesion molecule by normal and malignant myeloid progenitor cells because less than 15% of normal CD34 positive cells are CD54+ while greater than 85% of CD34+ acute myeloid leukemia blasts express the CD54 antigen. LFA-3, the ligand for CD2, is strongly expressed by erythrocytes, and these cells competitively inhibit killing of normal but not malignant clonogenic cells in an analogous way to the effects of monoclonal antibody to the CD2-LFA-3 adhesion system. The operation of this effect in vivo may be a basis for selective cytotoxicity by CD2+ LAK against clonogenic myeloid blast cells, and could be exploited further with infusion of appropriate monoclonal antibodies.

IL-4 acts as a homeostatic regulator of IL-2-induced TNF and IFN-gamma.

Interleukin-4 (IL-4) is a cytokine secreted by interleukin-2 (IL-2)-activated lymphocytes. IL-2-stimulated lymphocytes also secrete two cytokines, tumour necrosis factor (TNF) and gamma-interferon (IFN-gamma), which contribute to effector function and which may themselves recruit fresh, cytokine-secreting effector cells. We have now investigated whether the IL-4 induced is able to homeostatically regulate secretion of the TNF and IFN-gamma. Peripheral blood mononuclear cells or lymphocytes from normal donors and from patients with neoplastic disease were cultured in the presence of IL-2 alone, IL-4 alone or with both cytokines. IL-2 induced high levels of TNF and IFN-gamma secretion in both groups. The addition of recombinant IL-4 to these IL-2-stimulated cultures lead to significant inhibition of IFN-gamma and TNF production. IFN-gamma secretion was reduced by 50-99% in normal donors and by between 11% and 99% in patients (P less than 0.001). TNF levels induced by IL-2 were similarly reduced by IL-4 both in normal donors (P less than 0.003) and in patients (P less than 0.01). These inhibitory effects were produced by IL-4 at doses of IL-2 attainable in vivo. Inhibition appears to represent a homeostatic regulatory mechanism which may limit recruitment of fresh activated killer (AK) cells. When endogenous IL-4 activity in IL-2-activated lymphocytes was blocked by anti-IL-4 antibody, significantly higher levels of IFN-gamma and TNF were secreted (P less than 0.05). Since both TNF and IFN-gamma may contribute to the anti-neoplastic action of IL-2, manipulating the level of IL-4 activity in vivo could augment the benefits of IL-2 immunotherapy.

ALG/ATG treatment--a useful alternative for BMT in selected aplastic anaemia patients.

8 patients with severe and 4 with non-severe aplastic anaemia, aged 7 to 46 years, whose suppressor lymphocyte activity was in most cases elevated and who had no histocompatible sibling donor, underwent 1-2 courses of ALG/ATG treatment. 6 patients got CR and 1 PR and during 1-4 years they live with sustaining haemopoiesis, independent of blood transfusion (except one in PR). Among these seven responders increased suppressor lymphocyte activity normalized in 6. The adverse effects of the treatment were granulocyto- and thrombocytopenia, subfebrile states, hepatotoxicity, serum sickness and skin allergy. Five patients died because of early or late complications of the treatment or it's failure. Our results, similar to other authors', are like after BMT and supports the immunological mechanism of A.A. Immunosuppressive treatment with ALG/ATG has many advantages: no need to have identical bone marrow donor, no GVHD, possibility of treatment of patients over 30, even pretreated with blood transfusions, and finally much lower costs and efforts.

Bone marrow transplant recipients have defective MHC-unrestricted cytotoxic responses against cytomegalovirus in comparison with Epstein-Barr virus: the importance of target cell expression of lymphocyte function-associated antigen 1 (LFA1).

Cytomegalovirus (CMV) remains the most common single infective cause of death following allogeneic bone marrow transplantation (BMT) from major histocompatibility complex (MHC)-identical siblings, whereas Epstein-Barr virus (EBV)-related disease is infrequent. We show here that MHC-unrestricted cytotoxic effector cells in the peripheral blood of BMT recipients are highly effective at killing EBV-infected target cells, but are inactive against CMV-infected target cells. Differential cytotoxicity is associated with disparate target structure expression. Although both EBV- and CMV-infected target cells express viral antigens, it is only those infected with EBV that express the adhesion molecule lymphocyte function-associated antigen 1 (LFA1; CD11a/18). Thus, EBV-infected target cells are able to interact with the principal LFA1 ligand, intercellular adhesion molecule 1 (ICAM1; CD54), which is expressed on posttransplant peripheral blood mononuclear (PBM) effector cells. CMV-infected target cells cannot utilize this ligand. Posttransplant cytotoxicity against EBV-infected target cells is abolished by target and effector cell blockade with monoclonal antibodies (MoAbs) to LFA1 and ICAM1, respectively, demonstrating the functional relevance of this additional ligand interaction. These results provide an illustration both of the importance and of the limitations of MHC-unrestricted cytotoxicity in vivo and may explain the frequency of CMV disease and the relative rarity of EBV-related disease following allogeneic transplantation from MHC-matched siblings. The increased immunosuppression used following MHC-mismatched/matched unrelated-donor BMT may cause this MHC-unrestricted defense mechanism to fail and may contribute to the greatly increased incidence of EBV lymphoproliferative syndrome in these patients.