Pneumomediastinum as a complication to treatment of mediastinal (thymic) large B-cell lymphoma.

Mediastinal (thymic) large B-cell lymphoma (Med-DLBCL) is a subtype of diffuse large B-cell lymphomas (DLBCL) with a typical radiological appearance of bulky anterior mediastinal mass, often with areas of necrosis. We report a case of Med-DLBCL with unusual radiological findings and clinical development. Computed tomography (CT) obtained at presentation revealed a huge anterior mediastinal tumor with an axial diameter of 180 mm. Nineteen days after the first cycle of chemotherapy, chest radiography and CT revealed large areas of tumor necrosis and pneumomediastinum with air-fluid levels. To our knowledge, air-fluid levels inside Med-DLBCL have not been previously described. This finding, in combination with necrotic sputum, may indicate communication between the tracheobronchial tree and the tumor.

Chromosomal abnormalities and DNA image cytometry of haematological neoplasms in fine needle aspirates of lymph nodes.

The current diagnostics of haematological neoplasms along with morphological analysis, immunophenotyping and molecular analysis inevitably includes cytogenetic analysis. In this work the possibility of cytomorphological subclassification of haematological neoplasms from lymph node fine needle aspirates was examined without depending upon the referential histological diagnosis and cytogenetic analysis. In addition, the feasibility of cytogenetic analysis of the material obtained by lymph node fine needle aspiration (FNA) was examined. By analysing the findings of cytogenetic analysis and DNA image cytometry, it was decided to examine the possibility of comparing the findings and supplementing diagnostic possibilities of these methods. In 15 cases cytological diagnoses and cytogenetic analysis of haematological neoplasms were performed on the material obtained by lymph node FNA. In 12 of 15 cases histological diagnosis was made separately. A good cytohistological correlation was available in 9 of 12 cases (75%). Cytomorphological diagnoses in 10 of 15 cases (76%) were confirmed by the finding of a specific chromosomal translocation. In two cases cytological diagnosis did not correlate with the histological diagnosis and was confirmed only with specific chromosomal translocations. The lymphocytes obtained by lymph node FNA were adequate material for cytogenetic analysis - in 15 of 18 (83%) cases mitoses in cell cultures were obtained. In 13 of 15 (87%) cases clonal chromosomal abnormalities were detected, whereas in 2 of 15 (13%) cases a normal karyotype was found. DNA image cytometry was performed on nine samples, whereas in six samples the material was not sufficient. Although a small number of samples was analysed in the cases with identical cytomorphological diagnoses, the analysed histograms regarding the DNA index values showed heterogeneity. In conclusion, a cell culture sampled by FNA of lymph nodes is an adequate method for the chromosomal analysis. The specific cytogenetic abnormality associated with cytological diagnosis provides an opportunity to make a definitive diagnosis and provides a powerful approach when reference diagnosis on biopsy material cannot be obtained.

Prolegomenon for chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is a unique lymphoproliferative disorder that scarcely occurs under the age of 40; thereafter the incidence of CLL increases exponentially with age. CLL is characterized by progressive expansion of malignant CD5+ME+ B-cell clone accompanied by a myriad of cellular and humoral immune defects. Each of them might be linked to different clinically manifested complications such as increasing rate of infections, autoimmune disorders and disturbed immune surveillance against tumour cells. We assume that CLL occurs as a consequence of age-dependent, genetically related functional restrictions of the thymic microenvironment in supporting common lymphoid progenitor cells (CD5+ME+CD4-CD8-) to differentiate into mature T-cell and B-cell descendants. In conjunction with genetic abnormalities developing in B-cell progenitors, presumably expressing P glycoprotein (Pgp+), we postulate that developmentally altered T-cell descendants, along with quantitative imbalance among CD4+, their subsets and CD8+ lymphocytes in the peripheral blood, play an important additional role in facilitating the malignant B-cell clone emergence and in modulating the CLL clinical evolution. Namely, imbalance of any of T-cell-mediated cell interactive homeostatic mechanisms accompanied by imbalance in the production of various cytokines might in CLL influence leukaemic B-cell growth by deregulating inducer (c-myc and p53) and/or suppressor (bcl-2 and mutant p53) oncogenes responsible for the promotion or suppression of B-cell mitogenesis that may in turn further contribute to their impaired differentiation and/or differentiation arrest. In conclusion, CLL might be interpreted as a primary immunodeficiency syndrome developing in elderly population due to gradually evolving restriction of genetically controlled programs in the thymic microenvironment responsible for irregular maturation of common lymphoid progenitor cells that constitutively express CD5 antigen and ME receptor into T-cell and B-cell descendants.

Clinical tumor cell distribution pattern is a prognostically relevant parameter in patients with B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: B-cell chronic lymphocytic leukemia (B-CLL) cells are variably distributed among the major lymphoid compartments contributing to the heterogeneous clinical presentation and course of this disease. In order to evaluate this variable distribution we propose a model for its clinical assessment. DESIGN AND METHODS: We introduce the model for tumor distribution (TD) assessment based on TTM scoring system, where TD value represents percentage of total tumor mass infiltrating peripheral blood and bone marrow (TD=TM(1)/TTM). TD in B-CLL can be categorized into 3 subgroups: pure leukemia if TD=100%, predominantly leukemia if TD=50-99% and predominantly lymphoma TD<50%. RESULTS: Among 341 B-CLL patients there were 22.6%, 55.1%, 22.3%, pure leukemia, predominantly leukemia and predominantly lymphoma cases, respectively. TD parameter was strongly associated in univariate analysis with TTM size, Rai and Binet stages, spleen size and beta(2) microglobulin. TD was associated with response to therapy and survival, with higher TD values translated into higher response rates and longer survival. However, in univariate and multivariate Cox analysis TD displayed much stronger relationship with prognosis in female patients, where it is the strongest independent predictor of survival along with age and Binet stage. INTERPRETATION AND CONCLUSIONS: TD, a quantitative and simple clinical parameter, easily assessed in all patients, offers a reliable tool for evaluation of tumor cell distribution in B-CLL. It has independent and strong prognostic power in females, as opposed to males, possibly unmasking important, yet unrecognized, biological difference in B-CLL patients.

The relevance of multidrug resistance-associated P-glycoprotein expression in the treatment response of B-cell chronic lymphocytic leukemia.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether expression of P-glycoprotein (Pgp) is an intrinsic feature of B-lymphocytes in B-cell chronic lymphocytic leukemia (B-CLL) and how it correlates with hematologic indices and tumor load in the disease. Furthermore, the change of Pgp expression under cytotoxic treatment and its correlation to treatment outcome were studied. DESIGN AND METHODS: In 42 B-CLL patients, of whom 13 were sequentially monitored, expression of extracellular (MRK-16) and intracellular (C-219) Pgp epitopes on peripheral blood lymphocytes was determined by flow cytometry analysis and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis. RESULTS: Median RMF values in B-CLL patients were higher than in age-matched controls. Pgp expression did not correlate with any of the hematologic features or clinical stage of the disease. Patients who received some type of cytoreductive treatment prior to the study had lower Pgp values for both measured epitopes (median RMF for C-219 and MRK-16 of 1.99 and 2.03 in comparison to those of non-treated patients: 3.11 and 2.88, respectively). In 13 patients monitored during treatment the decrease in RMF was noted after treatment with chlorambucil, with RMF values for both Pgp epitopes decreasing in responders. This was in contrast to unchanged or even increased RMF values in those patients who did not respond to therapy. INTERPRETATION AND CONCLUSIONS: Our study confirms the importance of quantitative evaluation of Pgp expression by flow cytometry. At the clinical level, cross-sectional, single test evaluation of Pgp is of limited value whereas sequential follow-up values correlate with treatment response.

Knowledge of and attitudes to pharmacotherapy in medical inpatients.

OBJECTIVE: To analyze different aspects of patients' knowledge and attitudes to pharmacotherapy in medical inpatients. PATIENTS: 183 patients hospitalized in the Department of Medicine of University Hospital "Merkur", Zagreb, Croatia were investigated. METHODS: A questionnaire was designed to investigate patients' knowledge of drugs they were taking before admission to the hospital and drugs they are receiving during hospitalization. Patients were asked to give drug names, dosage and reasons for their prescription. Patients' rating of the importance of some drug characteristics (dosage, indication, precautions, side-effects, mode of action) was evaluated. RESULTS: A representative group of patients (mean age 55.5 years, range 17-86, SD 16.1; 89 men, 94 women; 50 hematological, 44 cardiological, 50 gastroenterological and 39 nephrological patients) showed a significantly better (p < 0.000001) overall knowledge of drugs taken prior to admission compared to the knowledge of drugs that they were receiving during hospitalization. Overall drug knowledge did not differ significantly between groups of patients stratified according to gender, ward, number of drugs they were taking or duration of treatment. In older patients (p < 0.0001) and in those with lower education (p < 0.001) a significantly worse overall knowledge was observed. On a 1-5 semiquantitative scale patients rated dosage as the most important and mode of action as the least important drug characteristic (average 3.62 and 2.08, respectively). Of all patients, 94.5% pointed out physicians as one of their sources of drug information, written drug information followed in 40.4% and pharmacists in only 11.5% of patients. CONCLUSIONS: Our results agree with the results of the few similar studies published to date. A need for better health education of patients is underlined and possible ways of providing drug information for patients are discussed. The need for improvement of physician-patient transfer of drug information as well as the need for written drug information tailored according to patients' needs is underlined.

Decision-tree approach to the immunophenotype-based prognosis of the B-cell chronic lymphocytic leukemia.

Use of a nonlinear prediction method, such as machine learning, is a valuable choice in predicting progression rate of disease when applied to the highly variable and correlated biological data such as those in patients with chronic lymphocytic leukemia (CLL). In this work, decision-tree approach to cell phenotype-based prognosis of CLL was adopted. The panel of 33 (32 different phenotypic features and serum concentration of sCD23) parameters was simultaneously presented to the C4.5 decision tree which extracted the most informative of them and subsequently performed classification of CLL patients against the modified Rai staging system. It has been shown that substantial correlation between the percentage of expression of the CD23 molecule on CD19+ B-cells, the level of sCD23, the percentage of CD45RA+, and the absolute number of CD4CD45RA+RO+ T-cells and the clinical stages, exists. The prediction vector, composed of their concatenated values, was able to correctly associate 83% of the cases in the low-risk group (Rai stage 0), 100% of the cases in the intermediate-risk group (Rai stage I and II), and 89% of the cases in the high-risk group (Rai stage III and IV) of CLL patients. Predictivity of this vector was 100%, 95%, and 89%, respectively. In conclusion, from the described analysis, it may be inferred that two processes play important roles in the progression rate of CLL: 1.deregulated function of the CD23 gene in B-cells accompanied by the appearance of its cleaved product sCD23 in the sera; and 2. functionally impaired and imbalanced CD4 T-cell subpopulations found in the peripheral blood of CLL patients.

High dose chlorambucil versus Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone regimen in the treatment of patients with advanced B-cell chronic lymphocytic leukemia. Results of an international multicenter randomized trial. International Society for Chemo-Immunotherapy, Vienna.

BACKGROUND: In recent years, much attention has been paid to the possible efficacy of intensive chemotherapy in the treatment of advanced, progressive B-cell chronic lymphocytic leukemia (CLL) patients. For this reason, the International Society for Chemo-Immunotherapy, Chronic Lymphocytic Leukemia Cooperative Group, has begun a randomized multicenter trial comparing Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen with continuous high dose chlorambucil (HD-CLB). METHODS: During the period January 1987 to May 1993, 228 previously untreated CLL patients from 7 cooperative institutions were randomized to this trial. Advanced and/or progressive disease was defined by high Total Tumor Mass (TTM) score (> 9), and/or short doubling time (DT) (< 12 months), and/or bone marrow failure. The response to therapy was defined by reduction of the initial TTM score. The end points of the trial were response rate, survival, and toxicity. RESULTS: HD-CLB resulted in a higher response rate than CHOP in evaluable cases, with 89.5% overall responses (complete response+partial response) versus 75%, respectively (P < 0.001). At the time of an analysis performed in July 1995 (after a median follow-up period of 37 months), overall survival was also longer in the HD-CLB treatment arm (median survival, 68 months) than in the CHOP treatment arm (median survival, 47 months) (P < 0.005). Toxicity was acceptable and comparable in the two treatment arms. CONCLUSIONS: The current study showed that HD-CLB is an effective and well-tolerated therapeutic option for patients with advanced and/or progressive CLL. Therefore, the authors recommend its wider use, possibly in comparison with and/ or in combination with new therapeutic agents, such as purine analogues.

A randomized phase II study on the effects of 5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin in patients with relapsed acute leukemia: an EORTC Leukemia Cooperative Group phase II study (06893).

5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin has been applied in a treatment protocol for patients with a relapse of acute myeloid or lymphocytic leukemia. Sixty-three patients received 5-Aza-2'-deoxycytidine 125 mg/m2 as a 6 h infusion every 12 h for 6 days in combination with either amsacrine 120 mg/m2 as a 1 h infusion on days 6 and 7 (n=30) or idarubicin 12 mg/m2 as a 15 min infusion on days 5, 6 and 7 (n = 33). Twenty-three patients (36.5%) obtained a complete remission (CR); eight of 30 patients treated with amsacrine and 15 of 33 treated with idarubicin. Patients with an interval of more than 1 year between initial diagnosis and start of the protocol achieved CR in 51.4%, compared to 15.4% for patients with an interval of less than 1 year. Patients with normal cytogenetics had a higher CR rate (61%) than those with abnormal cytogenetic findings (15.8%). Digestive tract and hematologic toxicity was prolonged, compared to standard induction schedules. Median disease-free survival was approximately 8 months, with only 20% of patients staying in remission for more than 1 year. 5-Aza-2'-deoxycytidine is a good antileukemic agent with considerable toxicity. Current results merit further investigations in previously untreated leukemia.

[Pseudothrombocytopenia caused by ethylenediaminetetraacetic acid (EDTA) (case report)]. / Pseudotrombocitopenija uzrokovana etilendiamintetraoctenom kiselinom (EDTA) (prikaz bolesnice).

Pseudothrombocytopenia is a laboratory artefact that can introduce serious problems in diagnosis and treatment in patients with low platelet count. The most common reason for this artefact is in vitro platelet clumping in blood samples collected into ethilenediaminetetraacetic acid (EDTA) anticoagulant. The clumping activity is greater at temperatures less than 37 degrees C, and the EDTA concentrations required for clumping are 20 times below anticoagulant concentrations. In this article we described the case of a female patient with diagnosed EDTA induced pseudothrombocytopenia. The cause of incorrectly low platelet counts was proved by simultaneous analysis in blood samples collected into EDTA anticoagulant and into heparin as a control sample. Absences of incorrectly low platelet count in heparin sample and rapid decrease of platelet count in EDTA sample were noticed. Decrease in platelet count was accompanied by increase in the number of leukocytes, so called pseudoleukocytosis. Careful examination of blood film is necessary to establish correct diagnosis, promptly after the blood collection and approximately two hours later. It is important to verify formation of clumps two hours after the blood collection and also progressive reduction in the platelet count in EDTA sample. By blood assessment conducted in this concern it is possible to avoid severe misinterpretation in such patients.

Autoimmune thrombocytopenia in adults: clinical experience.

Diagnostic and treatment algorithms in autoimmune thrombocytopenia (AITP) are still somewhat controversial. We present our experience in the diagnosis and treatment of 39 AITP patients, hospitalized at our department between 1990 and 1995, and discuss alternative approaches. There were 10 male and 29 female patients, median age 47 (range 18-75) years. All patients had isolated thrombocytopenia and normal or increased number of megakaryocytes in bone marrow. Platelet count lower than 15 x 10(9)/L was found in 25 (64.1%) patients. Eighteen (54.5%) patients responded well to standard and two (6.1%) to high doses of steroids, whereas 18.2% of the patients responded well to other immunosuppressive therapy. Antiplatelet antibodies were found only in 4 (10.2%) patients. Our conclusion was that a half of adult AITP patients achieve satisfactory recovery on standard doses of steroids.

[Case report of a female patient with autoimmune hemolytic anemia and cold agglutinin antibodies]. / Prikaz bolesnice s autoimunom hemolitickom anemijom s hladnim protutijelima.

We report a case of acute transient cold agglutinin disease, the etiology of which we could not determine with the available methods. Cold autoagglutinins had anti I specificity, high titers of the autoantibody (> 1:1,000) and the thermal range was relative wide. Our patient had severe haemolysis and immunosuppressive therapy with methylprednisolone and cyclophosphamide was administered. It is a question how much these immunosuppresive agents influenced the recovery, and in what extent it was a self limited disease with spontaneous recovery.

2-Chlorodeoxyadenosine treatment in non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia resistant to conventional chemotherapy: results of a multicentric experience. International Society for Chemo-Immunotherapy.

Among the purine analogs, 2-chlorodeoxyadenosine (2-CDA) is particularly effective for the treatment of hairy cell leukemia and Waldemstrom's macroglobulinemia. Both efficacy and toxicity of 2-CDA were evaluated in previously treated patients affected with chronic lymphoproliferative disorders such as low-grade non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). Thirty cases, mainly refractory, 16 affected with CLL, were included from six centers of the International Society for Chemo-Immunotherapy (IGCI). 2-CDA was administered in a 2 h i.v. infusion for 5-7 days at the standard dose of 0.1 mg/kg/day every 4 weeks. The median number of cycles was 3. Of 30 cases, eight (26.7%) achieved a complete remission (CR), nine (30%) a partial remission (PR), and two (6.7%) a minor response, while five cases (16.6%) did not respond, and six (20%) were considered early deaths. The overall response rate (CR + PR) was 56.7%, with a median response duration of 12 months (range 3-28 +) and a better response in CLL patients. Considering that the majority of patients were heavily pretreated, toxicity was acceptable, with 40% of cases not presenting any toxic effect. The main toxicity consisted in infectious complications. Based on the results of the present study, we confirm that 2-CDA is an effective drug in these lymphoproliferative disorders, suggesting its possible use either alone or in combination, also as first-line therapy.

Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG).

We conducted a prospective, multicenter pilot study of remission induction therapy in patients with poor prognosis MDS and AML evolving from a preceding phase of MDS. Fifty evaluable patients from 15 institutions were treated with one or two remission-induction courses consisting of i.v. idarubicin 12 mg/m2/day on days 1, 2, and 3 combined with a continuous i.v. infusion of cytarabine of 200 mg/m2/day on days 1 to 7. Of the 27 complete remitters (54%), 23 received a consolidation course which was identical to the remission-induction course except for the idarubicin 12 mg/m2 which was given on day 1 only. Fifteen patients received maintenance therapy consisting of six courses of cytarabine 10 mg/m2, s.c. twice daily, for 14 days. Two complete remitters were allografted and five patients received an ABMT. The median survival of all 50 treated patients was 14 months. The median duration of disease-free survival was 11 months with two patients in CR more than 2 years after entering CR. Twenty-four of the 27 remitters have relapsed. Four patients died during remission-induction therapy, but no patient died as a result of persisting hypoplasia. No fatal complications occurred during the consolidation and maintenance courses. Age and stage of disease had no significant impact on CR rate nor on remission duration. The CR rate was significantly (P = 0.03) higher in patients with only normal metaphases compared to patients with cytogenetic abnormalities. The DFS at 2 years was 33 vs 8%, respectively, for patients without or with cytogenetic abnormalities (P = 0.02). This study shows that patients below the age of 60 years with poor risk features are candidates for treatment with combination chemotherapy. A complete remission rate of more than 50% may be expected. Maintaining remission after remission-induction chemotherapy is a difficult issue. Patients not eligible for allogeneic BMT may be treated with intensive post-remission chemotherapy or autologous BMT.

Treatment of chronic lymphocytic leukemia in early and stable phase of the disease: long-term results of a randomized trial.

In 1982 the IGCI CLL cooperative group decided to investigate the usefulness of treating, at diagnosis B-cell chronic lymphocytic leukemia (CLL) in early and stable phase of the disease. From January 1982 to December 1986, 148 patients were randomized either to receive immediate treatment with chlorambucil (CLB) or to defer therapy to the time of progression. The early and stable phase of the disease was defined by a total tumor mass (TTM) score < 9, the absence of anemia or thrombocytopenia and a doubling time > 12 months. The main end-point of the study was survival. At the last evaluation in April 1993, after a median follow-up of 75 months, no significant difference was found in overall survival between early vs. deferred treatment patients from every cause of death as well as from death due to CLL-related causes only. The same results were obtained when the patients in more favorable stages, such as Binet stage A and TTM < 4.5, were considered. Interestingly, the incidence of epithelial cancer was similar in the two groups. Early treatment was associated with a significantly better response and a lower progression rate. From this long-term experience, it can be concluded that immediate chemotherapy with CLB is not beneficial for CLL patients in early and stable phase of the disease in terms of survival.

The differential diagnostic capacity of serum amyloid A protein between infectious and non-infectious febrile episodes of neutropenic patients with acute leukemia.

We studied the behavior of four major acute phase proteins (SAA, CRP, ACT and AGP) in pyrexial occurrences of 16 neutropenic patients with acute leukemia. Altogether 37 febrile episodes were recorded; 27 were infectious in origin (microbiologically documented infection and clinically documented infection, MDI/CDI group) and 10 were pyrexias of unknown origin (PUO group). In the MDI/CDI group the mean value for the highest individual SAA concentration was 282 +/- 161 mg/l and in the PUO group 95 +/- 79 mg/l. The corresponding mean values were 4.0 mg/l (range 0.2-5.5 mg/l) in 10 control patients with 1 year remission and 0.8 mg/l (range < 0.1-1.2 mg/l) in 30 healthy adults. The peak value of SAA rose above 100 mg/l in 85% of our MDI/CDI pyrexias and in 40% of PUO. More reliable results were obtained when the difference between the value on the day when pyrexia occurred and the previous day was calculated. In that case, the difference was above 75 mg/l in 23 of 27 (85%) MDI/CDI pyrexias and in none of 10 (0%) PUO. In the MDI/CDI group the mean difference was 204 +/- 137 mg/l while it was only 26 +/- 19 mg/l in the PUO group. The statistical significance was very high (p < 0.0001). The CRP monitoring was very inferior to SAA while ACT and AGP monitorings were unsatisfactory.

Myeloid hemopoietic growth factors. Review article.

The article is a critical review of recent publications on myeloid hemopoietic growth factors. They are glycoproteins that regulate the proliferation and differentiation of hemopoietic progenitor cells and the function of mature blood cells. They are also named colony stimulating factors after the experimental technique that led to their discovery. Myeloid growth factors are: granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF) and interleukin-3. Studies of hemopoietic growth factors in the past years have revealed many potential beneficial effects, but some limitations as well. They have been proved effective, above all, in neutropenic conditions of different origin. A large number of clinical trials have shown their beneficial effect in myelosuppressive conditions after cytotoxic chemotherapy, in post-transplant period in bone marrow transplantation procedures and in neutropenic conditions as part of other clinical entities. Although a number of studies that should determine their clinical role more clearly is still underway, it seems certain that myeloid hemopoietic growth factors already have an important role in modern pharmacotherapy.

Modalities of in vitro IgM and IgG production by peripheral blood lymphocytes of chronic lymphocytic leukemia patients and healthy volunteers.

In vitro spontaneous and mitogen (LPS, rIFN alpha and PWM) or cytokine (rIL-2) induced IgM and IgG production by peripheral blood lymphocytes of 15 CLL patients and 16 healthy volunteers has been determined. This study has shown: (1) that there is no difference between healthy donors and CLL patients in respect to level and variability of spontaneous immunoglobulin production by their lymphocyte cultures; (2) that there is no correlation between the percentage of B cells in individual cell cultures obtained from CLL patients and the amount of spontaneously produced IgM or IgG; (3) that there is a correlation between spontaneous in vitro IgM production and IgM content in the serum of the patient; (4) that in CLL patients selective augmentation of IgM production could be obtained after stimulation with PWM or rIL-2, but only in those cultures which spontaneously produce more than 35 ng/ml of IgM and (5) that the number of lymphocyte cultures able to be stimulated to IgM production is about 10 times smaller when they originate from CLL patients than from healthy volunteers. These findings are in line with the view that B cells in CLL patients often do not differentiate due to the insufficiency of factor(s) secreted by their own activated T-cells, but that in essence they follow the same differentiation pathway as normal B-cells.

Functional differences of T cells in B-chronic lymphocytic leukemia.

B cell chronic lymphocytic leukemia (B-CLL) is a disease characterized by an accumulation of monoclonal lymphocytes of B cell origin. Although the neoplastic process involves the B lymphocyte compartment, phenotypic and functional defects within the T lymphocyte population implicate their possible role in the pathogenesis of the disease. We analyzed the functional and morphological integrity of T lymphocytes from the peripheral blood of 64 patients with B-CLL. The activation of B-CLL T cells after PHA stimulation was determined by measuring [3H]-thymidine incorporation, assessing cell numbers in parallel cultures, and by monitoring the lymphocyte subsets during 9 days of cultivation. Our results indicate the presence of three functionally different populations of T cells in the peripheral blood of B-CLL patients. We present evidence for an increased proliferative potential of T lymphocytes from a group of patients with B-CLL.

A short multilingual quality of life questionnaire--practicability, reliability and interlingual homogeneity.

International cooperative clinical trials require a multilingual quality of life questionnaire. The 'International Society for Chemo- and Immunotherapy' therefore designed a study to develop and test a 'health accentuated' quality of life questionnaire in the eight languages spoken in this society. The objective was to examine practicability, reliability and interlingual homogeneity. Versions of the questionnaire in Czech, German, Hungarian, Italian, Kroatian, Polish, Romanian and Slovakian have been prepared. The results are based on data of 1,104 adult patients. They demonstrate that the developed questionnaire is practicable. Patients need 10-15 min to answer it, usually without assistance. The proportion of missing values is for all but two questions less than 3%. The questionnaire also found high acceptance reflected by only 2.7% refusals. It is reasonably reliable in each language. Interlingual homogeneity could be shown by demonstration of strong structural similarities between the different versions using multidimensional scaling, factor analysis and comparison of mean profiles.