Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL.

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.

Neoadjuvant therapy affects tumor growth markers in early stage non-small-cell lung cancer.

INTRODUCTION: While adjuvant therapy of early-stage non-small-cell lung cancer (NSCLC) is widely accepted, literature data concerning neoadjuvant treatment provide contradictory results with both improved and unaffected survival rates. Also, data concerning potential effects of neo-adjuvant therapy on cellular level are scarce. OBJECTIVE: The aim of present study was to analyze the effect of chemotherapy followed by surgical resection on several key biological markers of tumor growth (TGF-beta, VEGF), apoptosis (sAPO-1/Fas/CD95) and invasiveness (TIMP-1) assessed in the sera of NSCLC early-stage patients (IB-IIIA). - MATERIAL AND METHODS: Measurements were performed by ELISA method in blood serum from 24 NSCLC patients (I-IIIA) collected prior therapy, one day before surgery and 3 days after. RESULTS: TGF-beta serum concentrations were significantly lower after both chemotherapy (P<0.05) and surgery (P<0.01) in comparison to the baseline. VEGF levels decreased following NEO therapy with subsequent significant up-regulation after surgery (P<0.001). Interestingly, post-surgery serum VEGF strongly correlated with TGF-beta concentration (r = 0.52, P = 0.014). No significant differences were observed for serum sAPO-1/CD95/FAS as well as TIMP-1 concentrations at any of three evaluated time-points. CONCLUSION: Neoadjuvant treatment of early-stage NSCLC affects mostly mechanisms responsible for tumor growth and vascularization. Its effect on cancer cells apoptotic activity needs further evaluation.

Evaluation of fluorescence-based methods for total vs. amplifiable DNA quantification in plasma of lung cancer patients.

In the last decade numerous reports demonstrated that free-circulating DNA in plasma/serum samples might be a promising biomarker in a number of pathologies, including cancer. Thus, choosing the reliable and efficient method of plasma DNA quantification would be an essential step prior to any clinical evaluation of cell-free DNA measurement in cancer patients. The aim of present study was to compare two highly-sensitive DNA quantification methods in regard to their applicability and effectiveness in monitoring the cell-free DNA level in the blood of patients with resectable non-small cell lung cancer. Plasma samples collected from 10 patients before any treatment, after neoadjuvant therapy and subsequent surgery, were used for DNA quantification by direct fluorescent PicoGreen staining and by real-time qPCR in SYBR Green and TaqMan probe approach using beta-actin gene as the amplifying target. The PicoGreen method demonstrated a high level of correlation with both the SYBR Green (r=0.87, P<0.0001) and TaqMan probe approach (r=0.94, P<0.0001). The total DNA content, determined by PicoGreen, proved to be several-fold higher than the amplifiable DNA amount measured by real-time qPCR. Consequently, intercalating fluorochromes, like PicoGreen, might serve as a rapid, accurate, and inexpensive alternative to real-time qPCR for routine dsDNA quantification and multicenter standardization.

[Invasive aspergillosis in autopsy material of patients treated at the Institute of Tuberculosis and Chest Diseases during the years 1993-2000]. / Inwazyjna aspergiloza w materiale autopsyjnym u chorych leczonych w Instytucie Gruzlicy i Chorób Pluc w latach 1993-2000.

The aim of this paper is an analysis of clinical documentation and results of autopsy of 21 patients (pts) who died of invasive aspergillosis (IA) in the Institute of Tuberculosis and Chest Diseases in years 1993-2000 and the assessment of predisposing factors for IA. In 17 pts IA was the main and in other 4 only an accessory cause of death. All pts were treated with corticosteroids and/or cytostatic drugs--because of lung cancer (11 pts), cancer in other site (2 pts), haematologic disorders (2 pts), Wegener's granulomatosis (1 pt), polymyositis (1 pt), idiopathic pulmonary fibrosis (1 pt) and other diseases (3 pts). In 15 out of 21 pts granulocytopenia was revealed (from 0.008 x 10(9)/L to 0.82 x 10(9)/L) on an average one month before death. In 15 pts IA was limited to the lungs, in 6 others there were also fungal lesions in brain, kidneys, liver, spleen and heart. Pts with disseminated form of IA had significantly lower granulocyte count and were treated with higher doses of corticosteroids than others. Immunosuppressive drugs and granulocytopenia can be regarded as predisposing factors. Fatal course of IA depended also on the late diagnosis.

[Plastic bronchitis and mucoid impaction--uncommon disease syndromes with expectoration mucus plugs]. / Plastyczne zapalenie oskrzeli i zaczopowanie sluzem--rzadkie zespoly chorobowe przebiegajace z wykrztuszaniem odlewów oskrzelowych.

Mucoid impaction and plastic bronchitis are relatively rare disorders caused by the formation of obstructive airway plugs. We observed from February 1999 to June 2000 seven patients with mucoid impaction and one with plastic bronchitis. In the group of mucoid impaction there were 4 patients with bronchial asthma and 3 without history of lung disease. At the admission to hospital all patients suffered from cough, chest pain and effort dyspnea. Two of them expectorated during cough "bronchial casts". The chest X-ray of 5 patients revealed atelectasis of one of the lung's lobes and diffuse opacities in 2 others. In 4 cases during bronchoscopy one bronchus and in another three--numerous bronchi were obstructed with mucoid casts. Removing of the casts caused both the improvement of the patients' condition and withdrawal of atelectasis in 4 cases. In 5 patients the final diagnosis was allergic bronchopulmonary aspergillosis and in two mucoid impaction in the course of asthma without aspergillosis. Plastic bronchitis was observed in 44 years old man, who expectorated white, branching, bronchial casts for three months. On admission he was in respiratory failure. The chest X-ray revealed diffuse alveolar infiltrates and HRCT glass-ground opacities in both lungs and bronchiectasis in the middle lobe. The bronchofiberoscopy disclosed diffuse tracheobronchitis with casts occluding the middle lobe bronchus. Microscopic examination of the removed casts showed aggregates of mucus, macrophages, neutrophils and cells of respiratory epithelium. Precipitins against Aspergillus fumigatus were not found. Staphyloccocus coagulase (-) was cultured from urine and sputum specimens. We administered Vancomycin with Netylmycin, acetylocysteine, oxygen therapy and humid inhalation and the patient recovered. HRCT made six months after admission revelated total withdrawal of glass-ground opacities. The pathogenesis of plastic bronchitis in this case was unclear.

[The relation between lymphocyte profile in BALF and the course of sarcoidosis based on short term observation]. / Zaleznosc miedzy zawartoscia limfocytów w BALF a krótkotrwala obserwacja przebiegu sarkoidozy.

The aim of this study was to assess how the extent of the number and percentage of lymphocytes in BALF and also the CD4 to CD8 ratio can help to predict the short outcome in sarcoidosis. Material consisted of 74 patients, 39 men and 35 women in the age from 23 to 58 years. 11 patients had chest lesions in stage I, 43 in stage II and 20 in stage III. Clinical markers of activity (fever, erythema nodosum) were present in 22 cases. Extrathoracic lesion were present in 31 and abnormal pulmonary function in 30. In all patients BAL was done before treatment and lymphocyte count, percentage and CD4/CD8 ratio was calculated. 50 patients were treated with corticosteroids and 24 were observed without treatment. After 6-12 month of observation regression of sarcoid lesions was observed in 46 of 50 patients treated with corticosteroids and in 17 out of 24 patients observed without treatment. There were no differences in lymphocyte count and percentage in BALF and in the short term outcome between group treated with corticosteroids and without treatment. The patients in whom regression of lesions was observed have however significantly higher CD4/CD8 ratio than others.

[Value of the immunochromatographic assay for detecting IgG antibodies against 38 kDa mycobacterial antigen in diagnosis of tuberculosis]. / Przydatnosc testu immunochromatograficznego wykrywajacego przeciwciala IgG przeciwko antygenowi pratka 38 kDa w rozpoznawaniu gruzlicy.

Despite of a fast development in the techniques of rapid identification of mycobacteria by molecular genetic techniques, serodiagnosis may be of special values as non-expensive, easy to perform method. Several serodiagnostic tests, principally those using immunoenzymatic (ELISA) methodology are available. The goal of our study was to evaluate one step coloured immunochromatographic assay detecting IgG antibodies against antigen 38 kDa (Rapid Test TB). Our material consisted of 278 serum samples--tuberculosis (n = 155), healthy (n = 36), sarcoidosis (n = 50), lung cancer (n = 25) mycobacterial infections other than tuberculosis (n = 12). Tuberculosis group consisted of new culture positive cases (n = 66), new culture negative cases (n = 23), chronic cases (n = 43) and extrapulmonary TB (n = 23). Specificity of 96% and sensitivity of 54% was obtained. In pulmonary TB sensitivity of 50% and in extrapulmonary TB of 74% was obtained. In chronic cases sensitivity of 70% and in new cases of 40% was received. Sensitivity of 44% in new culture positive cases and 30% in new culture negative cases was obtained. We conclude that immunochromatographic test may be a very useful tool improving tuberculosis diagnosis, especially in extrapulmonary tuberculosis. Strip test may be an interesting alternative as it is an extremely simple, rapid, and cheap technique.

[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.

[Predisposing factors for bronchiectasis--analysis of 69 patients treated in the years 1995-1999]. / Czynniki predysponujace do powstania rozstrzeni oskrzeli--analiza 69 chorych leczonych w latach 1995-1999.

The aim of this study was to analyze the predisposing factors for bronchiectasis in 69 patients hospitalized in the 3rd Dept. of the Institute of TB and Lung Diseases in Warsaw in years 1995-1999. Bronchiectasis was diagnosed on the basis of the high resolution computed tomography (HRCT) scan. Among 69 patients at the age of 15-72 years there were 45 women (65%) and 24 men (35%). Fifty patients were nonsmokers. The most frequent predisposing factors of bronchiectasis in that group of patients were as follows: pneumonia (30.1%, in it recurrent pneumonia--19.3%, a single pneumonia--10.8%), sinobronchial syndrome (19.3%), pulmonary tuberculosis (12.1%), nontuberculous mycobacterial lung infections (7.2%), recurrent pneumonia and bronchitis in childhood (7.2%) and connective-tissue diseases (3.6%). Among other predisposing factors there were allergic bronchopulmonary aspergillosis, foreign body in bronchus, hypogammaglobulinemia and colitis ulcerosa.

[Infection as a main or additional cause of death in patients treated for small cell lung cancer]. / Zakazenia jako glówna lub dodatkowa przyczyna zgonu u chorych leczonych z powodu drobnokomórkowego raka pluca.

The aim of this study was to analyse the frequency of infection as a cause of death in small cell lung cancer (SCLC) patients. Our material consisted of 845 unselected SCLC patients, 246 women and 599 men, aged 29-78 years, treated between 1980-1994 in the Institute of Tuberculosis in Warsaw. 479 patients had limited and 366 extensive disease. 530 were in good (0-2) and 315 in bad (3-4) performance status. 784 patients died. Autopsy was done in 211 patients. Infection was regarded as a main cause of death in 39 patients (4.6%) and as a coexistent cause in 77 (9.1%). At the time of death from and/or with infection in 16 patients complete remission and in 27 partial remission of cancer was confirmed. The risk of death from and/or with infection was not related to the age and sex or to the performance status of patients and to extension of cancer. The risk of death from and/or with infection in the first 3 months of treatment was however greater for patients in bad performance status and with extensive disease and later (after 3rd months) for patients in good performance status and with limited disease.

[Pneumocystis carinii infections in patients with neoplasms and AIDS--clinical-pathologic changes in the lungs]. / Zakazenia pneumocystis carinii u chorych na nowotwory i AIDS--obraz kliniczno-patologiczny zmian w plucach.

Pneumocystis carinii (PC) has been documented as a cause of pneumonia in a broad range of immunocompromised patients. The presentation of disease will very based on the underlying predisposing condition but a confirmation depends upon the identification of organisms in a bronchial aspiration or lung biopsy specimen. This retrospective study based on autopsies of 15 patients (pts) with AIDS and 12 non AIDS pts with neoplastic diseases. Pneumocystis carinii pneumonia (PCP) was confirmed by histologic examination. The clinico-pathological analysis emphasizes a spectrum of morphologic variation of the disease in relation to the clinical course of a principal disease. A distinction was made between the microscopical diagnosis of PC infection in AIDS and non AIDS pts; the burden of organisms in infected AIDS pts appeared greater than that of neoplastic diseases (mostly with small cell lung carcinoma). Nonspecific features of diffuse alveolar damage associated with PC organisms were identified in 67% of non AIDS pts and 13% of AIDS pts. Various degree of interstitial fibrosis was more prominent in AIDS pts (67%) than in non AIDS pts. The high frequency of atypical changes in lung might be the result of various chemotherapeutic agents used in managing these pts or repeated pulmonary infections.

[Changes in the respiratory system of patients with rheumatoid arthritis--personal observations]. / Zmiany w ukladzie oddechowym u chorych na reumatoidalne zapalenie stawów--obserwacje wlasne.

13 patients with RA admitted to our Institute with symptoms of respiratory involvement were described. Taking under consideration pulmonary function tests, radiological findings and histological examinations, we recognised 7 cases with interstitial lung disease, 3 cases with recurrent respiratory infection with bronchiectasis, 1 case with pleuritis, 1 with Caplan's syndrome and 1 with alveolar haemorrhage. The role of RF, and treatment with gold in the development of interstitial lung disease, as well as character of physiologic abnormalities concerning the small airways and its potential connection with bronchiolitis were discussed.

[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.

[Our experience in bronchiolitis obliterans organising pneumonia (BOOP): personal experience]. / Bronchiolitis obliterans orginizing pneumonia--doswiadczenia wlasne.

BOOP is a disease with characteristic histology features which can occur as a secondary lung reaction to the various toxic agents or as a primary idiopathic disease. Idiopathic form of BOOP is a rare disease and may be found in 6-7 patients of 100,000 hospital admissions. We described 3 patients with idiopathic BOOP confirmed by the histologic lung examination. The time from the beginning of symptoms till the microscopical diagnosis ranged from 6 to 12 months. At the beginning of the disease the patients had symptoms compatible with the respiratory infection. In one of the patients the clinical course of the disease had a progressive character. In two patients spontaneous regression of radiological lung lesions was observed. This regression was however only temporary in one of them. In two cases treated by steroids regression of lung lesions was noticed.

Neuron-specific enolase (NSE) serum level in non small cell lung cancer--can it be an indicator of tumour chemosensitivity?

It is believed that the tissue or serum expression of neuroendocrine markers in non small cell lung cancer patients can implicate better prognosis in cases undergoing chemotherapy. The aim of the study was to assess the value of NSE serum level for anticipation of the tumor response to chemotherapy. We found elevated serum level of NSE in 34 of 60 patients (56.7%) at the time of diagnosis of inoperable non small cell lung cancer, significantly more often in those presenting stage IV of disease. In 21.7% partial response and in another 21.7% minimal regression was found after chemotherapy. Treatment results revealed no significant differences in respect to NSE serum level, however 77% of patients achieving partial response had elevated serum level of NSE.

CEA, NSE and SCC Ag in bronchial lavage in patients with lung cancer.

CEA, NSE and SCC Ag levels were measured in bronchial lavage (BL) and serum in patients with endobronchial lung cancer (LC) and in patients with nonmalignant lung diseases (NMLD). In both groups of patients 100 ml of normal saline solution was used during the lavage procedure. Tumor markers were detected using radioimmunoassay. CEA levels in BL and in serum were measured in 84 patients with LC and in 94 patients with NMLD. BL CEA levels were significantly increased in patients with LC (97.4 +/- 56.4 ng/ml) in comparison to patients with NMLD (4.2 +/- 6.3 ng/ml). Patients with LC had CEA levels in lavage fluid about 30 times higher than in serum. Significantly increased BL CEA levels in patients with LC were found in the cases with more advanced bronchoscopic tumor and in those with positive bronchial secretion cytology than in other groups of patients with LC. NSE levels were measured in BL and in serum in 21 patients with small cell lung cancer, SCC Ag levels were measured in BL and in serum in 21 patients with squamous cell carcinoma. The control group consisted of 28 patients with NMLD and 8 patients with adenocarcinoma. Determination of CEA levels in BL can be useful additional diagnostic method in patients with LC. The measurement of NSE and SCC Ag levels in BL in LC patients was considered to be not useful because of the low diagnostic sensitivity and specificity.

[The value of diagnostic methods used to assess the response to treatment in patients with limited small cell lung carcinoma]. / Wartosc metod oceniajacych odpowiedz na leczenie u chorych na ograniczona postac drobnokomórkowego raka pluca.

Tumor response is used as a main criterion whether or not the treatment yields an anticancer activity. The tumor response criteria are defined by WHO recommendation but little is known about the tests must be used. The aim of this paper was to compare the degree of response to the treatment of 268 patients with limited small cell lung cancer, using independently 3 methods: radiological, bronchoscopic and cytological of bronchial material. Particular categories of response (CR, PR NR and presence or absence of carcinomatous cells) were related to survival time of patients independently to method of assessment. Multivarinte Cox analysis selected 3 parameters related to 3 different methods as independent survival risk factors. We conclude that each of diagnostic method (chest x-ray, bronchoscopy, cytological examination of bronchial material yield independent information correlated with survival risk of particular patient.

The clinical value of Cyfra 21-1 estimation for lung cancer patients.

Cytokeratin-19, one of the cytoskeletal proteins, is expressed both in bronchial epithelium and in lung cancer cells. The aim of our study was to establish the value of serum cytokeratin-19 soluble fragment (Cyfra 21-1) measurement in lung cancer patients. Cyfra 21-1 levels were estimated in 35 patients (pts) with benign lung diseases and in 116 lung cancer patients: 55 pts with squamous cell lung cancer, 38 pts with small cell lung cancer and 23 pts with adenocarcinoma. The cutoff level was set at 4 ng/ml with a specificity of 94% and a sensitivity of 40%. Elevated Cyfra 21-1 values were found in 44% of squamous cell lung cancer, 39% of adenocarcinoma and 34% of small cell lung cancer pts (the difference was not significant). In squamous cell lung cancer and in adenocarcinoma elevated Cyfra 21-1 values were observed more often in patients with advanced disease than in patients with limited disease. There was no significant correlation between the initial Cyfra 21-1 level and the response to chemotherapy. Cyfra 21-1 was not a prognostic indicator, although in operable squamous cell lung cancer the proportion of survivors in the second year of observation was higher among the patients with normal preoperative Cyfra 21-1 levels.

[Value of determining the concentration of carcinoembryonic antigen in bronchial lavage for diagnosis of lung cancer]. / Wartosc oznaczania stezen antygenu rakowoplodowego w plynie z plukania oskrzeli dla rozpoznania raka pluca.

CEA levels were measured in bronchial lavage in 84 patients with endobronchial lung cancer, undergoing diagnostic bronchoscopy. The control group consisted of 94 patients with nonmalignant lung disease, in whom bronchoalveolar lavage was performed. In both groups of patients 100 ml of normal saline solution was used during the lavage procedure. CEA levels in lavage fluid and in serum were determined with polyclonal (CEA-RIA) and monoclonal antibodies (CEA-EIA). Significantly increased CEA levels in lavage fluid were observed in patients with lung cancer (97.4 +/- 56.4 ng/ml) in comparison to the patients with nonmalignant lung disease (4.2 +/- 6.3 ng/ml). Patients with lung cancer had CEA levels in lavage fluid about 30 times higher than in serum. Determination of CEA levels in bronchial lavage can be a useful additional diagnostic method in patients with lung cancer.

[Evaluation of the value of determining levels of cytokeratin-19 fragments for diagnosis of lung cancer]. / Ocena wartosci oznaczania stezenia fragmentu cytokeratyny-19 w rozpoznawaniu raka pluca.

Cytokeratins, the intermediate filaments, are expressed by many epithelial cells. Immunohistochemistry revealed the presence of cytokeratin-19 both in bronchial epithelium and in lung cancer cells. The aim of our study was to establish the value of serum cytokeratin-19 estimation by immunoenzymatic assay (Enzymun Cyfra 21-1, Boehringer Mannheim) in the patients (pts) with lung cancer (Ic). 153 pts (104 men, 49 women, median age 50 years) entered this study. The group consisted of 37 pts with benign lung diseases (control group), 56 pts with squamous cell Ic, 37 pts with small cell Ic and 23 with adenocarcinoma. Cut off value was determined at 4 ng/ml, with 96% of specificity. Elevated cytokeratin-19 values were found in 41% of pts with lung cancer (45% of squamous cell Ic, 39% of adenocarcinoma and 35% of small cell Ic). Median cytokeratin-19 values were 2.2 ng/ml in the control group, 3.4 ng/ml in squamous cell Ic, 3.3 ng/ml adenocarcinoma and 2.9 in small cell Ic. Cytokeratin-19 elevation was observed more often in non small cell Ic pts with advanced disease, stage III--46%, stage IV--50% than in early stages (I + II)--34%. In small cell Ic pts the frequency of cytokeratin-19 elevation was 20% in limited disease versus 45% in extensive disease. We conclude that cytokeratin estimation is not valuable in the recognition of histologic type of lung cancer, although elevated levels are seen more often in squamous cell Ic. Cytokeratin-19 estimation may be also helpful in lung cancer staging.