Quantitation of red cell-bound IgG by an enzyme-linked antiglobulin test in the patients with warm-type autoimmune haemolytic anaemia.

We have previously reported the evaluation of a gel-direct antiglobulin test and enzyme-linked antiglobulin test (ELAT) in the laboratory diagnosis of autoimmune haemolytic anaemia (AIHA). We now report our experience with quantitative ELAT performed on a large group of patients under long-term observation. The number of IgG molecules/red blood cell was determined in 658 blood samples from 268 randomly selected patients with warm-type AIHA. Eighty-six patients were tested every 2-4 weeks for several months. Laboratory signs of haemolysis were present in 65.7% of blood samples with a small amount of red cell-bound autoantibody (< 200 IgG molecules/red blood cell) and in 70.4% of blood samples with moderately coated red blood cells (200-1000 molecules/red blood cell). Haemolysis was demonstrated in 87.9% samples with > 1000 IgG molecules/red blood cell, which were predominantly IgG3 and C3 complement, the qualitative factors that may increase haemolysis. In 79% of periodically tested patients, the number of IgG autoantibody molecules/red blood cell decreased and this correlated with the improvement of haemolysis parameters. The number of IgG molecules varied in 21% of AIHAs and was associated with poor prognosis.

Effect of pamidronate on skeletal morbidity in myelomatosis. Part 1. The results of the first 12 months of pamidronate therapy.

BACKGROUND: Osteolytic bone destruction caused by increase of osteolytic activity is a major manifestation of multiple myeloma (MM). Pamidronate (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate) inhibits osteoclastic activity and reduces bone resorption. METHODS: Since October 1995 the efficacy of pamidronate is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. 46 patients with stage III myeloma and osteolytic lesions were randomized to receive either pamidronate (Aredia; Novartis) 60 mg i.v. in 4-hour infusion monthly (n = 23) or chemotherapy alone (control group n = 23). Estimation of performance status, quality of life, pain score, analgesic consumption, serum calcium concentration and twenty four-hours Calcium excretion, urine Calcium/creatinine ratio is done at least once a month (before pamidronate administration) while X-ray skeletal survey--before treatment and then every six months. RESULTS: In the first months of treatment apparent reduction of bone pain occurred. Hypercalcaemia was revealed in 6 patients at entry into the study. In 5 of these patients pamidronate restored and maintained normocalcaemia for a median 6 months. In 3 patients an aggressive plasma cell proliferation was accompanied by reoccurrence of hypercalcaemia. At skeletal X-ray examination performed after 6 and 12 cycles of pamidronate and by comparing each of consecutive imaging with previous one the progression of osteolysis was respectively found in 67% and 39% of patients. In the control group corresponding figures were: 79% and 70%. The mean number of skeletal events (pathologic fracture, radiation to bone and spinal cord compression) per year was lower in the pamidronate group (1.82) than in control-patients (2.72), p < 0.013. The proportion of patients who developed skeletal event (excluding vertebral fractures) was lower in the pamidronate group -34% v 52%. Adverse events of pamidronate: hypocalcaemia (< 2 mmol/l) observed in 7 patients occurred in particular patients beginning from 2 to 7 days after drug administration. In 2 patients hypocalcaemia that appeared in 24 hours after drug infusion was accompanied by blood pressure decrease; in one case systolic blood pressure dropped up to 60 mmHg, in the other one--to 90 mmHg. Muscular pain and fever up to 39 degrees C (transient and self-limiting "influenza like syndrom") occurred in 5 patients, in two patients after several hours and in three other--after some dozens of hours from drug administration. In one case hypertransaminasaemia was observed. CONCLUSIONS: In the first year of treatment monthly intravenous pamidronate administration as an adjunct to chemotherapy in patients with advanced multiple myeloma with osteolysis is an efficient approach in prevention and treatment of hyperacalcaemia, hypercalciuria and bone pain. It also shows some preventive effect on bone lesion occurrence.

Evaluation of the microcolumn technology for pretransfusion testing in multiple myeloma patients.

OBJECTIVE: Microcolumn tests are useful for serological investigations, although because of their high sensitivity, false-positive results might be expected, e.g. in hypergammaglobulinemia. The aim of this study was to evaluate these tests in multiple myeloma. METHODS: Pretransfusion testing was done in 80 patients with multiple myeloma using microcolumn and traditional tube tests. RESULTS: All sera were negative in microcolumn indirect antiglobulin test and enzyme test, positive in 58% of samples in the enzyme tube test. The microcolumn direct antiglobulin test was positive in about 40% of samples but never in the tube direct antiglobulin test. This was not due to the presence of autoantibodies but to nonspecific binding of immunoglobulins related to their concentration in sera. CONCLUSION: Microcolumn tests appeared to be useful for pretransfusion testing in multiple myeloma in spite of positive autocontrols.

Effect of recombinant human granulocyte colony stimulating factor on granulocytopenia induced by cytotoxic chemotherapy in patients with multiple myeloma.

15 multiple myeloma patients with severe granulocytopenia after chemotherapy were treated with recombinant human granulocyte colony stimulating factor (Neupogen; Roche). Granulocyte colony stimulating factor (G-CSF) was given s.c. usually in a dose of 5 micrograms/kg for 5-14 (median:8) days. In all cases the increase in ANC was observed; one day after completing therapy the ANC ranged from 2.3 to 19.7 (mean: 10.3) x 10(9)/l. In 3 cases the ANC peak appeared during first (2-4) days of treatment, in one- on 14-th day after 10-day unsuccesful treatment. Generally, ANCs rapidly decreased after discontinuation of treatment to the values observed prior to the last chemotherapy. Both adverse events present in 9 patients and changes in monitored blood biochemistry components were moderate and reversible. In 3 cases symptoms of myeloma progression occurred. The study showed that G-CSF is an efficient and well tolerated drug, but also demonstrated its short-term action.

Abnormal protein in the cerebrospinal fluid of patients with a submicroscopic X-chromosomal deletion associated with Norrie disease: preliminary report.

Norrie disease is an X-linked recessive disorder characterized by congenital blindness and, in many cases, mental retardation. Some Norrie disease cases have been shown to be associated with a submicroscopic deletion in chromosomal region Xp11.3. Cerebrospinal fluid (CSF) was collected from four male patients with an X-chromosomal deletion associated with Norrie disease. CSF proteins were resolved using two-dimensional gel electrophoresis and then analyzed by computer using the Elsie V program. Our analysis revealed a protein that appears to be altered in patients with Norrie disease deletion.

Separation of normal human erythrocyte membrane proteins by high resolution two-dimensional gel electrophoresis.

Different factors influencing two-dimensional gel electrophoresis of red cell membrane proteins were studied: membrane preparation and sample solubilization with a special regard to proteolytic artifacts, urea addition, slab gel acrylamide concentrations and silver staining methods. Spot patterns were analyzed both visually and by means of computer-assisted densitometry. A resolution of around 450 spots was achieved on 10% acrylamide slab gels. The reproducibility of the whole two-dimensional gel electrophoresis procedure was assessed by analysis of computer generated spot densities on gels which were run simultaneously with the same sample. It was shown that the standard red cell membrane preparation method does not lead to proteolysis, contamination by cytosolic proteins, or proteins from other cell types. In comparison with previous studies the relatively high resolution seemed to be due to a high solubilization efficiency combined with the use of a sensitive silver staining method.

[Therapeutic plasmapheresis in patients with multiple myeloma]. / Plazmafereza lecznicza u chorych na szpiczaka plazmocytowego.

The effectiveness of therapeutic plasmaphereses with antineoplastic chemotherapy was evaluated in 25 cases of plasmocytic myeloma in stage III of progression of the proliferative process. The indication to plasmapheresis was hypergelification of serum with clinical symptoms of central nervous system disturbances, renal failure in various stages of progression, intensification of coronary symptoms, bleeding tendency. Good effects with reduced level of total protein and monoclonal protein in serum by 30-80% with regression of clinical symptoms caused by serum hypergelification were obtained in 11 cases. In the remaining patients clinical improvement of varying degree was noted when the level of total and monoclonal protein in the serum fell by 10-29%.

[Chemotherapy and immunomodulating treatment of patients with multiple myeloma]. / Chemioterapia i leczenie immunomodulacyjne u chorych na szpiczaka plazmocytowego.

Prospective studies were carried out on the effectiveness of various treatment methods in 208 patients with plasmocytic myeloma. In 102 patients induction therapy was based exclusively on melphalan, in 106 cases polychemotherapy was used including vincristine, melphalan, carmustine, cyclophosphamide and prednisone. The differences in the per cent of patients with good response to treatment and in the survival time after treatment beginning were statistically not significant between these groups which suggests that polychemotherapy begun from the diagnosis of the disease is justified in patients with large mass of the neoplasm and poor prognostic factors. In 45 patients chemotherapy was supported by administration of immunomodulatory agents, including calf thymus extract in 25 cases, levamisole in 18 and interferon in 2. It was observed that maintenance of remission with chemotherapy and with immunomodulatory agents calf thymus extract or levamisole prolonged the survival of the patients. In cases of leucopenia the use of calf thymus extract facilitated chemotherapy by stimulation of myelopoiesis.

[Favism in Polish families]. / Fawizm w rodzinach polskich.

Four cases of fawism are presented. The disease was seen in one male patient, one homozygote and in 3 carriers of G6PD deficit. Diagnostic procedures, course of the haemolytic crisis in these patients, and possibility of prophylaxis in the families with fawism are discussed.

[IgM monoclonal gammopathy in plasmacytic neoplasms]. / Gammapatia monoklonalna IgM w nowotworach plazmocytowych.

In 331 patients with the diagnosis of multiple myeloma in 4 cases proliferation of plasma cells was associated with synthesis of a monoclonal IgM. In 3 of these cases coexistence was noted of features typical of multiple myeloma and Waldenström's macroglobulinaemia. In the clinical picture in two of these cases sings of blood hyperviscosity prevailed. These patients showed impairment of plasma clotting factors. The count of T and B cells in blood and the adherence and phagocytic activity of monocytes were not abnormal. The ultrastructural pattern of plasma cells in bone marrow was similar to that observed in classical cases of IgG or IgA multiple myeloma. In one case of lymphoplasmocytic proliferation with leucocytosis over 100 x 10(9)/l immunoelectroscopic examination of bone marrow cells demonstrated a formidable accumulation of the heavy chain of mu immunoglobulin in the cytoplasm of lymphoplasmacytes. In the serum and urine no monoclonal protein was found. In this case compression of vertebral bodies Th7 and L2 occurred.

Clinical-haematological analysis of 3321 cases of proliferative diseases of the haemopoietic system treated in the Institute of Haematology in the years 1951-1980.

The purpose of the study was assessment of the effectiveness of treatment applied in nine proliferative diseases of the haemopoietic system (PDHS) in the years 1951-1980. The effectiveness was determined comparing the mean survival time in each of these diseases in three 10-year-time periods characterised by essential changes in their treatment. Moreover, other factors were studied which may influence the survival time in these diseases. A continuing increase in the survival time correlated with advances in therapy was observed in acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), Hodgkin's disease (HD) and multiple myeloma (MM). An indicator of the advances in the treatment of acute leukaemias was also an over fourfold rise in the likelihood of achieving complete remission in the decade 1971-1980 in relation to two preceding decades. On the other hand, no improvement of the effectiveness of treatment was noted in chronic myeloid leukaemia (CML), polycythaemia vera (PV), myelofibrosis (MF) and non-Hodgkin lymphomas (NHL). The length of the survival time was influenced also considerably by patient's age (survival lower in old age), sex (better results in women) and place of residence of the patient (worse results in patients living in rural areas).

[Clinical usefulness of serum beta2-microglobulin determination in patients with multiple myeloma]. / Ocena przydatnosci klinicznej oznaczania stezenia beta 2-mikroglobuliny w surowicy krwi chorych na szpiczaka plazmacytowego.

Serum concentrations of beta 2-microglobulin (beta 2M) were determined in 73 patients with various forms of multiple myeloma and in various phases of the proliferative process. These determinations showed that beta 2M may be a useful indicator of changes in tumour mass and proliferation activity, and also an important prognostic factor. In patients with active proliferation the serum beta 2M concentration was significantly higher than in the group with stable proliferative process, and particularly in remission. A correlation was found between the serum concentration of monoclonal protein and beta 2M concentration. In the group with the secretory form of myeloma significant differences were showed in the length of survival which depended on beta 2M concentration in serum. The median survival of patients with beta 2M concentration in serum below 5.0 mg/l was 52 months and that in those with this concentration above 8.0 mg/l was 24 months.