Non-Hodgkin's lymphoma in patients with systemic lupus erythematosus.

Two cases of non-Hodgkin's lymphoma (NHL) associated with systemic lupus erythematosus (SLE) are described. Patient-1 was a 65-year-old woman in whom SLE and diffuse large B-cell lymphoma were concurrently diagnosed. The patient presented with low-grade fever, butterfly rash, arthritis and generalized lymphadenopathy without splenomegaly or bone marrow involvement. Complete remission of NHL and SLE was achieved with cyclophosphamide, adriamycin, vincristine and prednisone. Patient-2 was a 56-year-old woman in whom SLE had been diagnosed 14 years earlier. The patient presented with low-grade fever, bulky splenomegaly without lymphadenopathy, IgMA paraproteinemia, and expansion of a monoclonal CD19+/CD22+ lambda-type B-cell population in both bone marrow and peripheral blood. Diagnosis of a lympho-plasmacytoid lymphoma was established histologically after splenectomy. A partial remission of the neoplasm was achieved with cyclophosphamide, vincristine and prednisone. We suggest that the development of NHLs in patients with SLE may not be coincidental and we recommend the search for NHL in cases of SLE with prominent lymphadenopathy, massive splenomegaly or expansion of a monoclonal CD19+/CD22+ B-cell population.

Interleukin-6 and its relationships to acute phase proteins in serous effusion differentiation.

The aim of the study was to assess the discriminative power of cytokine interleukin 6 (IL-6) between transudative and exudative pleural and peritoneal effusions, and to compare IL-6 with common acute phase proteins in serous effusion differentiation. One hundred and forty-five consecutive patients with pleural or peritoneal effusion underwent diagnostic parecentesis. Patients were categorized in three groups. Malignant effusion (group A) 56 patients, non-malignant effusion (group B) 46 patients and transudate (group C) 43 patients. Serum and effusion levels of IL-6, C-reactive protein (CRP), alpha2-macroglobuline (alpha2-MG), alpha1-antitrypsin (alpha1-AT) and alpha1-acid glycoprotein (alpha1-AG) were determined. Serum IL-6 levels were significantly higher in groups A and B in comparison to group C (p<0.001 and 0.001, respectively). In addition, serum IL-6 levels were higher in group A compared to group B (p<0.001), while the studied acute phase proteins were not significantly different. All the studied parameters were higher in the effusions of groups A and B compared to group C. At a cut-off value of 72.1 fmol/ml IL-6 had a sensitivity of 82.6-89.3%, specificity of 88.4-90.7% and positive predictive value of 90.7-94.6% among the three groups. Our results suggest that IL-6 at levels > or =72.1 fmol/ml, alpha1-AT at > or =170 mg/dl and alpha1-AG at > or =52.3 mg/ml give strong evidences for malignancy in exudates.

Severe acquired hemophilia A successfully treated with activated recombinant human factor VII.

A case of acquired hemophilia A in a 65-year-old woman is presented. The patient had been subjected to cholecystectomy 2 months before the bleeding tendency appeared. On admission, she had easy bruising and prolonged activated partial thromboplastin time, but during hospitalization she had severe hemorrhage into the right gluteal and femoral muscles. An inhibitor of the factor VIII coagulant protein (FVIII:C) of high Bethesda titer was found in her serum. The patient was successfully treated with activated recombinant human factor VII (rhFVIIa) and immunosuppression. We conclude that rhFVIIa is a safe, effective, and fast-acting preparation for the treatment of severe hemorrhage in patients with acquired hemophilia A, and that the simultaneous administration of azathioprine and corticosteroids may suppress production of the inhibitor.

Prevalence of chronic idiopathic neutropenia of adults among an apparently healthy population living on the island of Crete.

The aim of the present study was to investigate the prevalence of chronic idiopathic neutropenia of adults (CINA) among an apparently healthy population born and living on the island of Crete. The study was carried out with 778 subjects, 392 men aged 16-78 years (median 43 years) and 386 women aged 15-79 years (median 40 years). All were employees of the Medical School or the adjacent University hospital and members of their families. Among these there were 64 subjects (8.23%) who fulfilled the diagnostic criteria of CINA applied in our department. Mild neutropenia (neutrophils 1700-2499/microl) accounted for 6.81% and moderate neutropenia (neutrophils 600-1699/microl) for the remaining 1.41%. No cases of CINA with severe neutropenia (neutrophils below 600/microl) were found. CINA was more frequent in women, with a women to men ratio of about 3:2. Approximately two thirds of the cases appeared in patients aged 30-59 years. Concomitant thrombocytopenia was found in three of the 64 subjects with CINA. Neutropenic subjects had chronic (perennial) rhinitis 3.4 times more frequently than non-neutropenics. No influence of occupation, use of insecticides and pesticides, contact with industrial chemicals, or administration of nonsteroidal anti-inflammatory drugs on the development of CINA was documented. We conclude that, despite the biased character of the study (population not randomly selected), our data provide a valuable estimation of the prevalence of CINA in the general population, given that our sample was sufficiently large, was derived from all major regions of the island, and was composed of subjects of both genders and of all age-groups from 15 to 79 years.

Elevated serum TNF-alpha concentrations are predictive of shortened survival in patients with high-risk myelodysplastic syndromes.

The levels of IL-1 alpha, IL-2, IL-6 and TNF-alpha were measured immunoradiometrically in the sera of 82 myelodysplastic (MDS) patients at diagnosis in an attempt to identify possible relationships between serum cytokine levels and clinical and laboratory parameters of the patients. We found that serum IL-6 and TNF-alpha concentrations were significantly higher in the group of MDS patients than in the normal controls (p < 0.03 and p < 0.001, respectively), while serum IL-1 alpha and IL-2 levels did not differ statistically between patients and control subjects. Elevated serum IL-6 and TNF-alpha concentrations were mainly seen in patients with high-risk myelodysplasia (MDS), i.e. patients with chronic myelomonocytic leukemia (CMML) (p < 0.05 and p < 0.001, respectively), refractor anemia with excess of blasts (RAEB) (p < 0.01 and p < 0.001, respectively), or refrochopy anemia with excess of blasts in transformation to acute leukemia (RAEB-t) (p < 0.001 and p < 0.001, respectively). Patients with low-risk disease, i.e. patients with refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS), had serum cytokine levels comparable to those of controls. Patients' serum IL-6 and TNF-alpha correlated inversely with the hemoglobin concentration (p < 0.01 and p < 0.05, respectively) and positively with the absolute number of circulating myeloblasts (p < 0.01 and p < 0.001, respectively) and the proportion of bone marrow (p < 0.001 and p < 0.001, respectively) myeloblasts. A negative correlation was also noted between serum TNF-alpha concentrations and patients' survival in high-risk MDS (p < 0.02). We concluded that elevated serum IL-6 and TNF-alpha values are seen mainly in patients with high-risk disease, and that high serum TNF-alpha concentrations are predictive of shortened survival in this group of patients.

Defective natural killer cell activity of peripheral blood lymphocytes correlates with the degree of neutropenia in patients with chronic idiopathic neutropenia of adults.

Natural killer cell activity (Nka) of peripheral blood mononuclear cells (PBMCs) against K562 cell targets was assessed in 66 patients with chronic idiopathic neutropenia of adults (CINA) using the 16-h 51Cr-release assay. It was found that CINA patients exhibited significantly lower Nkr than normal subjects, which strongly correlated with the degree of neutropenia and the numbers of circulating neutrophils. Patients' NKa was increased by recombinant human interleukin-2 (rhIL-2) or recombinant human interferon-alpha (rhIFN-alpha), but the values obtained did not reach the respective NKa values found in normals. However, percentages of cytokine-induced rises of NKa did not differ statistically between patients and normal subjects. No serum inhibitors of NKa were demonstrated in our patients. CINA patients had low numbers of circulating NK cells as defined by the expression of NK-cell-related surface markers CD16, CD56, and CD57. CD16+ and CD56+, but not CD57+, cells correlated with the values of baseline NKa. The numbers of all these cell subsets correlated with the degree of neutropenia and the numbers of circulating neutrophils. Using CD56+-enriched PBL suspensions, it was shown that patients' NK cells displayed normal tumor cell binding capacity and produced in vitro normal amounts of natural killer cytotoxic factor(s) against K562 cell targets upon activation with rhIFN-alpha. Finally, percentages of perforin-expressing and granzyme B-expressing CD16+ cells did not differ statistically between patients and normal controls. Based on all these observations, we concluded that CINA patients display low NKa probably because they have low numbers of circulating NK cells. No functional abnormalities of NK cells were demonstrated. The cause and the underlying mechanisms leading to NK-cell depletion in these patients remain to be clarified.