Adult T-cell leukaemia and lymphoma: report of two cases and a brief review of the literature.

Human T-cell lymphotropic virus type 1 (HTLV-1) can cause adult T-cell leukaemia/lymphoma (ATLL). Two patients originating from the Caribbean area with ATLL are described. The first patient developed respiratory insufficiency due to acute T-cell leukaemia. The diagnosis was suspected because of characteristics of abnormal lymphocytes in the blood smear. The second patient had lymphadenopathy and developed severe hypercalcaemia. Both patients were typical cases of ATLL. The pathogenesis, clinical manifestations, pitfalls and treatment of this intriguing disease are discussed.

[Renal insufficiency due to light chain multiple myeloma]. / Nierinsufficiëntie door neerslag van lichte ketens bij multipel myeloom.

In 3 female patients, aged 65, 83 and 76 years, with severe renal failure, light chain multiple myeloma was diagnosed, following a substantial delay on the part of the doctors concerned. Either the diagnosis had not suspected or the serum proteins had been misinterpreted. After a while, the first two patients declined further treatment with chemotherapy and haemodialysis, and subsequently died. The third patient attained a creatinine clearance of 20 ml/min and was subsequently treated for the multiple myeloma in the outpatients department. The absence of a paraprotein peak in the serum does not exclude the possibility of a multiple myeloma. In the case of light chain disease, the gammaglobulin region is, in fact, often empty. Treatment of multiple myeloma consists of a rapid rehydration and forced diuresis; the usefulness of plasmapheresis has not been demonstrated.

[Pleural amyloidosis as a cause of excessive pleural effusions]. / Amyloïdose van de pleura als oorzaak van overmatig veel pleuravocht.

A 83-year-old woman known with a stable disease multiple myeloma was hospitalized frequently with dyspnoea caused by copious bilateral pleural effusions. Thoracentesis was performed repeatedly but pleural effusions returned. Extensive laboratory and radiological examinations failed to reveal the cause of the pleural effusions. Finally, after pleural biopsy the diagnosis of amyloidosis of the pleura could be made. The patient died in hospital from a stroke. Pleural amyloidosis is rarely reported and is accompanied by large uni- or bilateral pleural effusions even without amyloidosis of the heart.

Parotid mass as first symptom of a malignant lymphoma.

BACKGROUND AND OBJECTIVES: Primary malignant lymphoma in the parotid gland is rare and seldom described in the literature. We studied the medical history and outcome of seven patients with a primary malignant parotid lymphoma. We looked for prognostic variables and for different behavior of these lymphomas in comparison to lymphomas in the usual sites. METHODS: Between 1985 and 1995, we conducted a retrospective study of the medical histories of malignant parotid tumors operated at our hospital. There were 18 malignancies, of which 7 were primary malignant lymphomas. We classified them according to Rosenberg et al. [Blood 1994;84: 1359-1392]. Outcome and survival time were compared with malignant lymphomas in usual sites. Further we looked for possible prognostic factors. RESULTS: We found an unusually high percentage of primary malignant lymphomas in the parotid gland in our series: 38% of all malignancies. Histological workup showed one Hodgkin lymphoma, two marginal zone B-cell non-Hodgkin lymphomas, two lymphoplasmocytoid non-Hodgkin lymphomas, and two follicular non-Hodgkin lymphomas. The clinical course of these lymphomas is comparable to that in lymphomas in the usual sites. CONCLUSIONS: Primary malignant lymphomas in the parotid gland have no different behavior compared to lymphomas in usual sites. There are no prognostic variables that distinguish a malignant lymphoma in the parotid gland. The only difference is a rather difficult operation to obtain a histologic specimen.

The effects of interleukin-3, GM-CSF, and G-CSF on the growth kinetics of colony-forming cells in myelodysplastic syndromes.

In order to obtain more insight into the nature of the abnormal in vitro colony formation in myelodysplastic syndromes (MDS), we investigated the kinetics of the colony formation of 23 MDS cases in response to recombinant human interleukin-3 (IL-3), Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating Factor (G-CSF), and giant cell tumor cell line conditioned medium (GCT-CM). The kinetics of GCT-CM-induced colony formation were comparable to that of G-CSF-induced colony growth, both in MDS and in normal bone marrow cultures. Colony formation was found to be delayed in MDS. The delay in colony formation was most apparent in the GCT-CM (G-CSF) responsive progenitor cell compartment. In MDS cases with clinical features of high risk disease, this delay was more pronounced as compared with low risk cases (7 and 3 days, respectively, in response to GCT-CM). The delay in colony formation was found to be caused by an increase in the time interval before progenitor cells had begun to divide. These results suggest that a prolongation of the time spent in G0 of myeloid progenitor cells in MDS may be the cause of the indolent in vitro colony formation observed in this disease.

Thrombocytopenia associated with gold therapy: a drug-induced autoimmune disease?

We studied 13 patients with rheumatoid arthritis (RA) and gold-induced thrombocytopenia. Platelet-specific autoantibodies of the IgG and often also of the IgM class were detected by immunofluorescence on the patient's platelets and in ether eluates from these platelets. In nine patients we also detected autoantibodies in the serum. The antibodies were unreactive with platelets from patients with Glanzmann's disease in most cases, and were not EDTA dependent. Thus, they had the serological characteristics of true autoantibodies. The reaction of the antibodies with platelets was not influenced by the addition of extra gold. By atomic absorption spectrophotometry we found that the ether eluates, which were often strongly reactive with donor platelets, were free of gold. This indicated that the autoantibodies in the thrombocytopenic patients were not dependent on gold for their reaction. The possibility is raised that gold treatment of rheumatoid arthritis patients induces or enhances the formation of platelet-specific autoantibodies, and that gold-induced thrombocytopenia is a drug-induced autoimmune disease.

Chronic idiopathic and secondary neutropenia: clinical and serological investigations.

Clinical data on 49 patients with chronic idiopathic neutropenia (CIN) and 42 patients with neutropenia secondary to a well-defined immunological disorder (SN) were collected and related to serological parameters. In 47% of the patients with CIN and 53% of those with SN, a positive direct immunofluorescence test was obtained with granulocytes from the patients. In the sera from the patients in the two groups, antibodies against donor granulocytes were detected by the indirect immunofluorescence test, the leucoagglutination test and/or the granulocytotoxicity test in 15%, 19% and 15%, respectively. The results of the above tests could not be correlated with any clinical or haematological parameter. Immune complexes in the serum were detected by the 125I-Clq-binding test in 29% of patients with CIN and in 58% of those with SN. The presence of serum immune complexes correlated well with the existence of a low neutrophil count, but not with the presence of recurrent infections, with bone-marrow abnormalities, or with positive reactions in other serological tests. The sera of eight out of 14 patients with CIN and seven out of 12 patients with SN had inhibitory activity for myeloid colony formation in vitro (CFU-GM). This CFU-GM inhibitory activity was correlated with the presence of recurrent infections and with hypoplasia of the myeloid compartment of the bone marrow, but not with positive reactions in other tests. We conclude that the 125I-Clq-binding test probably detects circulating immune complexes that induce a shift neutropenia, whereas serum activity inhibitory for CFU-GM possibly relates to clinically more serious forms of neutropenia. The significance of neutrophil-bound Ig and granulocyte-reactive antibodies in the serum is not clear.

Lymphoid proliferations in the orbit: malignant or benign?

Clinical, pathological, and immunological analysis of 20 patients with ocular adnexal lymphoid disease has demonstrated several parameters which are useful for distinguishing malignant from benign lesions. Patients in the fourth or fifth decade of life presenting with an acute history of pain, oedema, epiphora, double vision, and ptosis, with a mass localised in the lacrimal gland area, are more likely to have a pseudolymphoma or a chronic inflammatory lesion than a true non-Hodgkin lymphoma (NHL). It is not possible to obtain a definite diagnosis without surgical intervention, because only three out of nine patients with orbital NHL had evidence of a monoclonal B cell population in peripheral blood on admission to the Orbital Centre. Furthermore it was confirmed that the identification of the various orbital lymphoid infiltrates becomes more distinct when immunological techniques are added to the clinical and histopathological methods of investigation. Multidisciplinary cooperation leads to further improvement of diagnosis and treatment of ocular adnexal lymphoproliferative disease.

Serological studies in patients on platelet- and granulocyte-substitution therapy.

A serological follow-up study was undertaken in 47 patients with bone-marrow failure, who were repeatedly transfused with random donor granulocytes and/or platelets. Sera, obtained at regular intervals, were investigated in the leucoagglutination test, the lymphocytotoxic test and the immunofluorescence test on paraformaldehyde-fixed platelets, granulocytes and lymphocytes. The frequency of alloimmunization was high (73%). Not only HLA antibodies, but also blood-cell-specific alloantibodies were detected in the sera of the alloimmunized patients, e.g. lymphocyte-specific, platelet-specific and granulocyte-specific antibodies. The immunofluorescence test on platelets was also used as a crossmatch, and when this test was positive it was always found that after platelet transfusion the increment value was nil.

The Evans syndrome: characterization of the responsible autoantibodies.

The immunofluorescence test on paraformaldehyde-fixed cells was used for the detection of antibodies bound to the platelets and granulocytes and present in the sera of 24 patients with Evans syndrome and a further 29 patients with both idiopathic thrombocytopenia (ITP) and idiopathic neutropenia (INP), but without autoimmune haemolytic anaemia (AIHA). The direct immunofluorescence test on platelets and/or on granulocytes was positive in all patients with a cytopenia, but the sera of only 17 patients with the Evans syndrome and 15 of the other patients contained platelet- or granulocyte-specific autoantibodies. From absorption and elution experiments, it appeared that the autoantibodies were directed against antigens specific for the various peripheral blood cells, i.e. erythrocytes, platelets and granulocytes and that they were not cross-reacting.

Myocardial protection with cold cardioplegia in a patient with cold autoagglutinins and hemolysins.

A technique is described for providing myocardial protection with cold potassium crystalloid cardioplegia in a patient with cold autoagglutinins and hemolysins. The patient was only mildly cooled systemically. The coronary system was perfused with a normothermic cardioplegic solution to remove the blood before the cold cardioplegia was started. The heart was rewarmed with a normothermic cardioplegic solution before the blood was reintroduced. With this technique, the patient underwent an uneventful coronary bypass operation.

Primary and secondary autoimmune thrombocytopenia. A serological and clinical analysis.

In 357 thrombocytopenic patients, the autoimmune nature of the thrombocytopenia was established with the immunofluorescence test on paraformaldehyde-fixed platelets in suspension (PSIFT). In 142 patients, autoimmune thrombocytopenia (AITP) was accompanied by (an)other disease(s) and thus classified as secondary AITP. No significant difference was found in the distribution of the immunochemical characteristics of the autoantibodies between primary and secondary AITP. The results of survival studies with 51Cr-labelled platelets and organ sequestration measurements in 7 patients with idiopathic thrombocytopenia purpura (ITP) indicated that platelets with IgM autoantibodies were sequestered mainly in the spleen. An increased incidence of AITP was seen at 5 to 10 years of age, in the 3rd decade and in the 6th and 7th decades of life. AITP was slightly more common life in females. The following groups of accompanying diseases in 142 AITP patients were distinguished: autoimmune diseases of the blood, malignant diseases of the blood, generalized and organ-specific autoimmune diseases, carcinoma and a miscellaneous group of diseases. No significant differences were found in the immunochemical properties of the autoantibodies between the various categories of disease. In 7 cases, AITP was preceded by an established viral disease, in 1 case by lepra and in another by a vaccination. The PSIFT was found to be a suitable test for diagnosing AITP not only in idiopathic thrombocytopenia, but also in thrombocytopenia associated with another disease.

Autoimmune haemolytic anaemia with monoclonal IgM (kappa) anti-P cold autohaemolysins.

A patient is described with immunoblastic non-Hodgkin's lymphoma and autoimmune haemolytic anaemia of the cold autoantibody type. The autoantibodies were monoclonal IgM-kappa cold haemagglutinins/haemolysins with blood-group specificity, anti-P. Red-cell autoantibodies directed against blood-group-P antigen have until now only been detected, as polyclonal IgG antibodies, in paroxysmal nocturnal haemoglobinuria.

Pseudothrombocytopenia: an immunologic study on platelet antibodies dependent on ethylene diamine tetra-acetate.

Antibodies specifically reacting with platelets only in the presence of EDTA, by the platelet immunofluorescence test, were found in the serum of 20 patients with pseudothrombocytopenia due to in vitro EDTA-dependent platelet agglutination. These antibodies reacted optimally at 0-4 degree C. In 19 patients, IgG antibodies were detected; in 8 patients, IgM or IgA antibodies were also found. In one patient, only IgM antibodies were found. In 14 patients, the IgG antibodies were IgG1, but IgG2, IgG3, and IgG4 antibodies were also seen in 7 patients. The reaction of platelets with the antibodies was detectable in the presence of Na2EDTA, the K, Ca, and Mg salts of EDTA, and K2EGTA. F(ab')2 or F(ab') fragments of the IgG antibodies reached as strongly as the intact antibodies, indicating that the reaction is dependent on the antibody-combining site. The EDTA-dependent antibodies did not show platelet-group specificity. However, platelets from patients with Glanzmann disease did not react with the antibodies.

Immune Unresponsiveness to platelets. A case study.

Both 51Cr-survival studies with donor platelets and allogenic skin transplantations were performed in a patient with immune unresponsiveness to platelet antigens, i.e., HLA-and platelet-specific antigens. The patients, who suffered from hypoplastic anaemia, was successfully transfused with random donor platelets during 13 months. The serum of this patient contained only granulocyte-and mononuclear-cell-reactive antibodies, but no platelet-reactive antibodies. A nearly normal survival time of the donor platelets as well as a prolonged rejection time of a skin allograft of the same donor support the serological findings. The 51Cr-platelet survival time was not influenced by a leucocyte concentrate from the same donor, which was administered at the same time. Thus, in our patient, no increased platelet destruction could be induced via the so-called innocent bystander mechanism.

Post-transfusion purpura: a serological and immunochemical study.

By applying the platelet suspension immunofluorescence test (PSIFT), platelet-specific alloantibodies responsible for post-transfusion purpura were detected in eight patients within a period of 2 years. All patients were female and had previously received blood or had been pregnant. The platelet-specific alloantibodies had the specificity anti-Zwa in all the patients, who were all Aw(a-). In two patients the platelets were tested in the acute phase of the disease and found to be coated with IgG. In one patient an ether eluate was prepared from the platelets that reacted strongly with Zw(a+) platelets, but weakly with platelets from Zwb-homozygous individuals. The sera of these two patients, and of two others whose platelets were not directly tested, taken in the acute phase of the purpura, reacted strongly with Zwa-positive platelets. The four sera also reacted, however weakly, with Zwa-negative platelets, with autologous platelets taken during remission and with platelets from patients with Glanzmann's disease. It is postulated that Zwa-anti-Zwa complexes, present in the eluate and the sera, caused the reaction with Zwa-negative platelets and the patients' own platelets. Immunochemical characterization of the post-transfusion purpura antibodies showed that in all patients these were IgG, in two combined with IgM antibodies. Antibodies of the sub-class IgG1 were found in all patients, sometimes together with IgG3. In the indirect immunofluorescence test with anti-complement serum, the PTP antibodies in only four sera were able to fix complement. In only two of these sera were these complement-binding antibodies detectable in the 51 Cr-lysis technique and then in a much lower titre than in the immunofluorescence technique.