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At least 37 records · Page 2Linked to original sources
PubMed1985

The prognostic value of serum beta 2 microglobulin compared with other presentation features in myelomatosis.

The levels of serum beta 2 microglobulin, blood urea concentration, serum creatinine, haemoglobin and performance status have been measured in 476 patients in the Medical Research Council's 4th trial for myelomatosis. Levels of serum beta 2 microglobulin were also subsequently measured in 208 patients who achieved a stable "plateau" condition. Serum beta 2 microglobulin levels, uncorrected for serum creatinine, were found to be the single most powerful prognostic variable available at presentation. Multivariate analysis showed that only the addition of haemoglobin levels could improve upon this and the improvement, though statistically significant (P = 0.006), appeared to be of much less clinical value. The prognostic value of serum beta 2 microglobulin at plateau appeared to be equally large for a given difference in value, but the variability between patients was much less at that time. Serum beta 2 microglobulin would appear to be a key measurement for assessing the prognosis and response to treatment in patients with myelomatosis.

Creatinine↗
PubMed1982

Long-term survival in myelomatosis. A report to the MRC working party on leukaemia in adults.

The patients entered into the Medical Research Council's First Myelomatosis Trial (MRCI) have been followed up for a minimum of 12 years, and an attempt has been made to define features recorded at presentation that might predict long-term survival and to estimate the risk of acute myeloid leukaemia (AML) induced by treatment with either of the alkylating agents, melphalan or cyclophosphamide. In this series, the chance of a patient surviving 5 years was strongly related to the haemoglobin, blood urea concentration (BUC) and performance status at presentation. Other features, including paraprotein levels, type of heavy or light chain, bone lesions and recovery of polyclonal immunoglobulin added little useful information. Six patients died of AML, all after more than 4 years in the trial; the incidence of AML among 4-year survivors was 10%. All six patients had been treated with continuous melphalan and the implications of this for future chemotherapy for myelomatosis are discussed.

Aged↗
PubMed1991

Refractory myelomatosis treated with mitoxantrone in combination with vincristine and prednisone (NOP-regimen): a phase II study. The Nordic Myeloma Study Group (NMSG)

In a phase II study, patients with refractory myelomatosis were treated with a combination chemotherapy (NOP regimen): mitoxantrone (bolus injection of 4 mg/m2 on days 1-4), vincristine (continuous infusion of 0.4 mg/24 h on days 1-4) and prednisone (250 mg/d on days 1-4 and 17-20). The treatment was repeated every 4 weeks. Ninety-two patients were treated after they were found refractory to treatment with melphalan and prednisone (and occasionally vincristine) (n = 50) or more intensive treatment regimens (n = 42) including anthracyclines (n = 18). Response (greater than or equal to 50% reduction of M protein) was obtained in 23 patients and minor response (clinical improvement but less than 50% reduction in M protein) in 22 patients. The median duration of the response was 7.5 months. Equal response rates were observed irrespective of the type of previous treatment. The major toxicity was myelosuppression with severe granulocytopenia and infections. However, the frequency decreased throughout the cycles. The NOP treatment is recommended in refractory myelomatosis, especially in patients refractory to other intensive regimens. Patients in a poor clinical condition or with thrombocytopenia before treatment should have a reduced mitoxantrone dose in the first treatment cycles.

Adult↗
PubMed1975

Cytogenetic studies in myelomatosis.

Cytogenetic studies have been carried out on bone marrow aspirates from 25 patients with myelomatosis. Abnormal stem lines were present in 7 of the patients; the remainder had a diploid chromosome complement. In most patients - also in those without an abnormal clone - some metaphases had a blurred appearance similar to that seen in bone marrow aspirates from patients with acute leukaemia. In many of the chromosome preparations obtained before cytostatic therapy some metaphases with structural aberrations on the chromosomes were seen. Evidence is presented that in the patients with abnormal stem lines in the bone marrow, the chromosome abnormalities are confined to the myeloma cells and are not found in the erythrocytic or granulocytic precursors, which thus do not seem to be involved by the neoplastic process. Based on the present resuts and on a review of the relevant literature some general cytogenetic features are emphasized which may contribute to a better understainding of the disorder. Especially, it is demonstrated that in myelomatosis the cytogenetic changes are much more uniform than in other malignant disorders with the exception of chronic myeloid leukaemia.

Adult↗
PubMed1977

Serum erythropoietin in myelomatosis.

Erythropoietin activity in serum was measured using 59Fe incorporation into erythrocytes in protein-starved, hypoxic mice. The activity in serum from 20 patients with untreated myelomatosis was not significantly different from that in 31 saline controls. Only three patients had detectable erythropoietin levels in serum: 0.24 IU/ml, 0.27 IU/ml and 0.50 IU/ml (standard B), respectively. The venous haematocrit was correlated positively with the glomerular filtration rate as measured by 51Cr EDTA-clearance. No correlation could be established between venous haematocrit and serum albumin or serum transferrin. The results are in agreement with the assumption of a defective erythropoietin activity due to renal failure in myelomatosis.

Erythropoietin↗
PubMed1978

Interrelationships between Vitamin B12 and folic acid in myelomatosis: cobalamin coenzyme and tetrahydrofolic acid function.

Cobalamin and folate metabolism was investigated in 43 patients with myelomatosis, in 8 control subjects of similar age and 22 younger controls. Plasma total cobalamin was lower in myeloma patients than in either of the control groups and methylcobalamin (Me-Cbl) was disproportionately reduced. Erythrocyte levels of total cobalamin were very similar in patients and elderly controls but were half the levels in younger controls. Erythrocyte levels of Me-Cbl were slightly higher in patients than in the dlderly controls. FIGLU excretion after L-histidine was elevated in 53% of the patients but values did not correlate with serum or erythrocyte folate or with plasma total cobalamin. FIGLU excretion decreased after DL-methionine or Me-Cbl only in patients whose FIGLU excretion was initially high. The results are discussed in the light of the 'methylfolate trap hypothesis' and suggest that some patients with myelomatosis have insufficient activity of methionine synthetase to meet the additional metabolic demand for one carbon compounds.

Adolescent↗
PubMed1979

Quantitation of erythropoiesis in myelomatosis.

Quantitation of the erythropoiesis with radio-iron (59Fe) was applied to 9 patients with untreated myelomatosis. The method included blocking of the 59Fe reutilization by injection of non-radioactive iron. There was no uniform pattern in the Fe-kinetics values. The Plasma Iron Turnover (PIT) and the Red Blood Cell Iron Turnover (RBCIT) varied from subnormal to values markedly increased above upper normal limit. The calculated average Mean Red Cell Life time (MRCL) of erythrocytes was just below normal range. The mean Marrow Transit Time (MTT) was normal in the patients, despite subnormal venous haematocrit, indicating insufficient stimulation of the bone marrow. The renal function, measured as 51Cr-EDTA clearance, was found positively correlated to the RBCIT (r = 0.78, P less than 0.05). The results suggest that the previously demonstrated relationship between anaemia and renal failure in patients with myelomatosis is caused mainly by an inability of the bone marrow to produce sufficient red blood cells under the stress of anaemia related to the degree of renal impairment.

Aged↗
PubMed1983

Antibody response to pneumococcal vaccination in patients with myelomatosis.

17 patients with myelomatosis were vaccinated with a 14-valent pneumococcal capsular polysaccharide vaccine. In comparison to 12 healthy controls, they had statistically significant lower combined geometric mean antibody concentrations (the geometric means of all 14 antigens), both before and 4 weeks after the immunization. Mean antibody increases, however, were remarkably similar in the 2 groups. After 18 months the geometric mean antibody concentrations of the patient group had returned to preimmunization levels or lower for 7 out of 14 antigens. 1 case of pneumococcal bacteraemia occurred in the patient group 8 1/2 months after vaccination in spite of a significant initial antibody response against the infecting serotype 23 F. Pneumococcal vaccination in patients with myelomatosis appears to yield subnormal antibody responses and therefore probably insufficient protection against pneumococcal infection.

Aged↗
PubMed1985

Classification and prognostic variables in myelomatosis.

It is difficult to compare the results of treatment obtained in different trials in myelomatosis because different sets of diagnostic criteria are used, and because the criteria by which patients are deemed eligible for entry vary. Thus the composition of different series of patients varies considerably. Furthermore, the outcome of treatment is recorded in different ways. Uniformity in the diagnostic categories entered would reduce the variance in survival between different trials: for example, trials in myelomatosis should exclude patients with monoclonal gammopathy of uncertain significance, non-progressive or indolent myeloma, extramedullary plasmacytoma, and plasma-cell leukaemia. The subdivision into simple prognostic groupings such as those proposed by the Medical Research Council is helpful in interpreting the survival patterns in different trials in which the proportions of patients in different prognostic groups are likely to vary. These groupings and other staging systems do not correlate with responsiveness to treatment. Rapid responders fare worse than slow responders, and this might provide a basis for a second randomisation to test whether a change in treatment could benefit the rapid responders.

Clinical Trials as Topic↗
PubMed1985

Development of acute nonlymphocytic leukaemia (ANLL) in myelomatosis.

On the basis of the literature, so-called secondary acute nonlymphocytic leukaemia (S-ANLL) in myelomatosis is reviewed. Using the banding technique, cytogenetic changes including hypodiploidy and partially or totally missing chromosomes # 5 and # 7 are recorded. The findings are in accordance with the cytogenetic changes seen in S-ANLL in other malignancies which have been treated with cytostatics, especially alkylating agents. So, S-ANLL in myelomatosis seems to be a result of treatment with cytostatics, though a causal relationship has to be documented.

Acute Disease↗
PubMed1989

Renal failure in myelomatosis.

Renal failure is a common presenting feature in myelomatosis. This review offers a practical means for classifying renal failure in this disease. Three groups are identified: (1) those patients whose renal failure improves or is stable when they are maintained on a high fluid intake; (2) the minority of patients whose renal failure progresses despite high fluid intake; and (3) those patients who are fluid-intolerant due to oliguric renal failure or congestive cardiac failure. The difference between groups 1 and 2 is not simply due to differences in response to chemotherapy, for many group-1 patients achieve improvement in renal function without or before loss of light chain proteinuria. It is concluded that all patients with myelomatosis with excess monoclonal free light chain proteinuria are at risk from developing renal failure of the type associated with group 1. The chances of them doing so are diminished if they maintain a high fluid intake. Group 2 encompasses a range of conditions not all of which are clearly defined. There is generally a poor correlation between the physical characteristics of light chains and the presence of group-2 renal failure.

Acute Kidney Injury↗
PubMed1969

Urography in myelomatosis.

To investigate whether urographic contrast media might precipitate Bence Jones protein in the renal tubules and lead to renal failure in patients with myelomatosis, the reaction between the media and myeloma urine was studied in vitro. Appreciable precipitation was found only in urine at or below pH 4.5, and its occurrence did not correlate with the type or concentration of protein present. It is concluded that the risk of urography in myelomatosis is very small.

Acute Kidney Injury↗
PubMed1984

Analysis and management of renal failure in fourth MRC myelomatosis trial. MRC working party on leukaemia in adults.

During March 1980 to February 1982, 73 out of 80 patients in renal failure admitted to the fourth MRC myelomatosis trial were managed by a planned policy of high fluid intake (greater than or equal to 3 1/24 h) in addition to receiving one of the two chemotherapeutic regimens being tested in the main trial. Patients were also randomised to receive either sodium bicarbonate to render their urine neutral or no supplement. Follow up continued till death or to April 1983. Of 49 patients who survived more than 100 days, 39 achieved reversal of their renal failure (18 complete, 21 partial). Recovery of renal function, as assessed by a fall in the serum creatinine concentration, was achieved even when light chain proteinuria persisted. Partial recovery of renal function was associated with prolonged useful life in several patients. In only 14 of the 80 patients studied was death directly attributable to renal failure. Survival of patients in the study was appreciably better than in equivalent groups of patients in other MRC trials in which less stringent policies of fluid intake were used. Patients randomised to receive alkali fared marginally better than the others, but the difference was not significant. These results show that in many cases patients with myelomatosis who develop renal failure may have this complication reversed by taking a high fluid intake. Furthermore, though light chain is an essential component of renal disease in these patients, other factors are also important and are accessible to treatment.

Acute Kidney Injury↗
PubMed1970

Thromboembolic complications in myelomatosis.

Fourteen cases of myelomatosis associated with major thromboembolic complications are reported. Six patients died of pulmonary embolism, seven had deep-vein thrombosis as a presenting symptom, and three had evidence of amyloidosis. A preliminary estimate of the incidence of thromboembolism based on 376 patients admitted so far to the Medical Research Council's myelomatosis trial is about 3%, while pulmonary embolism accounted for about 3% of all deaths. Possibly a hypercoagulable state and the presence of amyloidosis may be important in the pathogenesis of this complication.

Adult↗
PubMed1969

Adult Fanconi syndrome and multiple myelomatosis.

A case is described of a 59-year-old woman presenting with multiple renal tubular defects. The aminoaciduria was of a generalized type. When investigated initially the only feature of myelomatosis was urinary Bence-Jones protein. Two years later radiologically classical multiple myelomatosis developed and rapidly progressed to the patient's death nine months later.

Amino Acids↗
PubMed1981

Relative importance of renal failure and increased bone resorption in the hypercalcaemia of myelomatosis.

In order to define the relative importance of renal failure and increased bone resorption in the hypercalcaemia of myelomatosis 22 untreated patients were studied, of whom 12 were hypercalcaemic. Most patients had malabsorption of radiocalcium from the gastrointestinal tract and evidence of increased bone resorption as assessed by fasting urinary hydroxyproline/creatinine ratio. The mean OHPr/Cr ratio, however, was similar in patients with and without hypercalcaemia. Renal failure and Bence Jones proteinuria occurred more frequently in the hypercalcaemic patients. In four patients with hypercalcaemia there was an increase in OHPr/Cr after saline infusion accompanied by an improvement in renal function and hypercalcaemia. Mithramycin given to the same patients further reduced hypercalcaemia, presumably by inhibiting bone resorption. It was concluded that the hypercalcaemia of myelomatosis is due to the combination of renal failure and increased bone resorption, but that the OHPr/Cr ratio in the untreated state is a poor indicator of the degree of bone resorption in hypercalcaemic patients.

Acute Kidney Injury↗
PubMed1984

Proximal renal tubular function in myelomatosis: observations in the fourth Medical Research Council trial.

Proximal renal tubular function was studied in 522 consecutive patients entered into the Medical Research Council's fourth myelomatosis trial. Assessment was made at presentation after a 48 h period of hydration but before administration of chemotherapy. The most common abnormalities in the urine other than light chain proteinuria were raised concentrations of the low molecular weight proteins alpha 1-microglobulin and alpha 1-acid glycoprotein. These were usually accompanied by increases in urinary beta-N-acetyl-D-glucosaminidase concentrations. The concentration of these substances in the urine directly correlated with urinary free light chain output. This tubular proteinuria was seen whether or not patients had impaired glomerular function, as assessed by a rise in serum creatinine concentration. Urinary concentrations of retinol binding protein, however, were generally increased only when serum creatinine concentrations were raised. This applied even when there were high concentrations of light chains, alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase in the urine. There is therefore a selective tubular proteinuria in myelomatosis which is seen in almost all patients with urinary light chain values greater than 1 u/l. This proteinuria is generally reversible, when light chains no longer appear in the urine. Patients whose serum creatinine was greater than 200 mumol/l, however, had increased urinary output of retinol binding protein in addition to increased excretion of alpha 1-microglobulin, alpha 1-acid glycoprotein, and beta-N-acetyl-D-glucosaminidase. Tubular proteinuria in many of these patients presenting in renal failure persisted even when light chain output was reduced after chemotherapy.

Acetylglucosaminidase↗
PubMed1989

Bulky extramedullary plasmacytomata: rare mode of relapse in myelomatosis.

In two cases of myelomatosis relapse was accompanied by the development of bulky extramedullary plasma cell tumours, which created serious management problems. In both cases the histology was of a poorly differentiated plasmacytoid tumour with frequent mitoses. In one case paraprotein had completely disappeared from the serum and urine after six months' treatment with melphalan alone but did not correlate with improved survival. It is concluded that extramedullary spread of myelomatosis in the form of bulky tumour deposits is a rare and ominous mode of tumour progression or relapse. Rises in serum and urinary paraprotein concentrations are not the inevitable signs of relapse.

Cecal Neoplasms↗