[The MEDGER document. A new document for cooperation between internal medicine and geriatrics].
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
G Brenning
Publications and source records attributed to G Brenning.
Natural interferon-alpha in combination with melphalan/prednisone versus melphalan/prednisone in the treatment of multiple myeloma stages II and III: a randomized study from the Myeloma Group of Central Sweden.
Three hundred thirty-five previously untreated patients with multiple myeloma in clinical stages II and III entered a randomized trial comparing intermittent oral melphalan and prednisone (MP) therapy (n = 171) with MP in combination with natural (leukocyte-derived) alpha-interferon (MP/IFN) (n = 164). The treatment groups were comparable with regard to major prognostic factors. The response frequency was 42% in the MP group and 68% in the MP/IFN group (P < .0001). Eighty-five percent of IgA myelomas and 71% of Bence-Jones myelomas responded to MP/IFN compared with 48% and 27%, respectively, to MP treatment (P = .001). There was no difference in the overall survival between the two treatment groups. However, the survival of 72 patients with IgA or Bence-Jones myeloma randomized to receive MP/IFN was significantly longer (median 32 months) than that of 71 patients treated with MP (median 17 months) (p < .05). No statistically significant difference in response frequency (60% v 46%) or survival was found for patients with IgG myeloma. Hematologic toxicity, WHO grades III and IV, was higher in the MP/IFN group (48%) than in the MP group (33%) (P < .05) during the induction treatment period. Flulike syndrome was observed in 68% of patients receiving MP/IFN. The results show that MP/IFN is a well-tolerated treatment regimen, superior to MP for remission induction, and it improves significantly the overall survival for patients with IgA and Bence-Jones myelomas.
Adult↗
Etoposide, doxorubicin, cyclophosphamide and high-dose betamethasone (EACB) as outpatient salvage therapy for refractory multiple myeloma.
Fifty-six patients with refractory multiple myeloma were treated with intermittent courses of etoposide, doxorubicin, cyclophosphamide and high-dose betamethasone (EACB) every 4th week. The overall response rate was 30%. Durable remissions exceeding 1 year were obtained in 12 of the 17 responding patients. A significant prolongation of the survival time was found for responding patients (median 13 months) compared to those patients who did not respond (median 9 months) to EACB therapy (p = 0.01). A low frequency of neutropenic fever episodes was noted compared to other salvage treatment regimens. The EACB regimen was usually well tolerated and could be administered safely on an out-patient basis. This regimen might be an alternative especially for elderly patients unresponsive to initial therapy.
Actuarial Analysis↗
Treatment of multiple myeloma with interferon alpha: the Scandinavian experience.
IFN alpha is a biologic therapeutic agent with documented antitumoral effect in multiple myeloma. 15% of previously untreated myeloma patients achieve a clinical response to IFN alpha alone with a possible dose-response relationship. A particularly good effect is noted in IgA myelomas treated with natural IFN alpha. A randomized study was started in April 1986 comparing melphalan/prednisone (MP) therapy with MP plus natural IFN alpha (MP/IFN) in untreated patients with multiple myeloma stages II and III. 220 patients had entered the study by autumn 1989. An interim report is given here. The response frequency was 48% in the MP group and 66% in the MP/IFN group (P less than 0.02). Stage II patients responded better to MP/IFN (76%) than to MP alone (48%) (P less than 0.01). No significant difference was noted for stage III patients. 91% of all IgA myelomas responded to MP/IFN and 52% to MP (P less than 0.01). The difference in response frequency of IgG and BJ myelomas between the two treatment groups was not statistically significant. The observation period is still too short to draw firm conclusions on survival. However, a statistically significant longer response duration time and survival from response (P less than 0.01) was noted for stage II patients.
Antineoplastic Combined Chemotherapy Protocols↗
Oral versus intravenous melphalan and prednisone treatment in multiple myeloma stage II. A randomized study from the Myeloma Group of Central Sweden.
Eighty-one previously untreated patients with multiple myeloma stage II entered a randomized trial comparing oral melphalan (0.25 mg/kg/day; n = 40) with intravenous melphalan (0.125 mg/kg/day; n = 41) in combination with oral prednisone (2 mg/kg/day). The courses were given for 4 days and repeated every sixth week. The treatment groups were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, the response duration times and the survival times. No significant difference in nonhematological and hematological toxicity was noted. Since intravenous administration of melphalan did not result in a substantial increase in response rate or survival, this study supports the use of oral melphalan/prednisone as first-line therapy for patients with multiple myeloma.
Actuarial Analysis↗
Alternating combination chemotherapy (VMCP/VBAP) is not superior to melphalan/prednisone in the treatment of multiple myeloma patients stage III--a randomized study from MGCS.
86 previously untreated patients with multiple myeloma stage III entered a randomized trial comparing combination chemotherapy (VMCP/VBAP) (n = 42) with intermittent oral melphalan and prednisone (MP) treatment (n = 44). The treatment gropus were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, 52% (VMCP/VBAP) vs 61% (MP); in the response duration times, median 19 months vs 22 months, or in the survival times, median 24 months vs 28 months. However, survival of patients older than 65 years was significantly shorter in the VMCP/VBAP group (median 15 months) compared to the MP group (median 23 months) (p = 0.03). No significant difference in non-hematological or hematological toxicity was noted. The study further supports the notion that MP therapy should be used as primary standard treatment for patients with multiple myeloma.
Adult↗
Induction treatment with alpha-interferon in multiple myeloma: an interim report from MGCS.
A randomized study comparing melphalan/prednisone (M/P) therapy with MP + natural alpha-IFN in untreated patients with multiple myeloma stages II and III started April 1, 1986. By March 1989, 78 patients were evaluable in the MP group and 80 in the MP/IFN group. 48% of the MP patients achieved a response and 66% in the MP/IFN group (p = 0.04). Stage II patients responded better to MP/IFN (76%) than MP alone (47%) (p = 0.02), while no statistically significant difference was noted for stage III patients. 90% of the IgA myelomas responded to MP/IFN and 52% to MP (p = 0.02). Both for IgG and BJ myelomas the response rates of MP/IFN were higher than of MP, although the differences were not statistically significant. The observation period is still short. There was no difference in total survival between the two treatment groups. However, in patients less than or equal to 65 years a tendency to a longer survival was seen for those receiving the IFN combination (p = 0.12).
Antineoplastic Combined Chemotherapy Protocols↗
Biochemical markers in multiple myeloma: a multivariate analysis.
The analysis of individual biochemical and clinical variables in 121 patients with multiple myeloma showed that serum beta 2-microglobulin (S-beta 2m) had the most significant relation to survival. Other variables such as serum thymidine kinase (S-TK), serum lactate dehydrogenase (S-LDH), S-creatinine, haemoglobin (Hb), ESR, S-albumin, age and clinical stage were also significant. No such relationship was found with M-component, presence of light chains in urine, type of secreted immunoglobulin or S-calcium. The exclusion of clinical stage in the first multivariate analysis resulted in a model consisting of S-beta 2m, age and S-TK, none of the other variables gave additional information. When in the second multivariate analysis the basic variables involved in staging procedure were excluded and clinical stage included, stage III, but not stage II, was found to give additional information to the model described above. Individual analysis of the variables showed that Hb had the most significant relation to effect of initial therapy. Other significant variables were S-TK, S-beta 2m and age. When using the multivariate approach, Hb alone was found to contain all the relevant information.
Adult↗
IgE-producing low-grade non-Hodgkin lymphoma.
An unusual case of IgE-producing non-Hodgkin lymphoma (NHL) is presented. The patient's history included a 6-year period of increasing IgE level before a low grade NHL was diagnosed. The patient developed lymph node, skin, bone marrow and lung infiltrations. With a cytostatic combination therapy a temporary improvement was achieved, but the patient died from progressive disease after 2 yr. The morphological appearance of the tumour varied between that of LP immunocytoma and a centrocytic lymphoma. Immunophenotype studies showed intracytoplasmic IgE lambda in tumour cells and B-cell surface phenotype (BB-1 pos; OKT 10 pos; PCA weakly pos and SIgE lambda).
Aged↗
High doses of natural alpha-interferon (alpha-IFN) in the treatment of multiple myeloma--a pilot study from the Myeloma Group of Central Sweden (MGCS).
alpha-interferon (alpha-IFN) is a biological response modifier with a dose-dependent activity. The present study on the treatment of patients with multiple myeloma with high doses of natural alpha-IFN was designed to meet this dose-dependent concept. 50 previously untreated patients with IgA and BJ myelomas and a s-Creatinine less than or equal to 200 mumol/l entered the study. Various treatment schedules were tested. The initial plan was to give the patients 30 X 10(6) U alpha-IFN daily. This dosage, however, gave unacceptable toxicity. Step-by-step decreasing dose schedules were given to the patients, 10 X 10(6) U of alpha-IFN daily for 7 consecutive d repeated every 3rd week was found to be the maximal tolerable dose that could be given to most patients. 36% (95% confidence levels: 22%-50%) of the patients responded: 41% of the IgA myelomas and 23% of BJ myelomas. Median time to response was 1.5 months and median response duration was 20 months. Impaired general condition and central nervous system and gastrointestinal-related toxicity were the main adverse reactions. Hematological side-effects were mild.
Aged↗
Influence of interferon on the growth of primary ovarian carcinoma cells in a semi-solid agar system: comparison with clinical effects of interferon therapy.
The sensitivity of primary human ovarian cancer cells to interferon (IFN) was studied in vitro by the use of a tumor cloning system in semi-solid agar. Tumor colonies were found in 37% (34/93) of the experiments with tumor cells from ascites and in 35% (6/17) of the experiments with solid tumors. The relative colony-forming ability could not be correlated to prior treatment. In 15 out of 18 patients the ascitic tumor cells were sensitive to IFN-alpha. Sensitivity was found in one test out of three with solid tumors. The sensitivity was dependent on the dose of IFN but could vary for the natural IFNs alpha and gamma. In seven patients the relation between in vitro and in vivo sensitivity of the tumor cells to IFN could be studied. Any correlation between in vitro and in vivo sensitivity could not be revealed in this small group of patients.
Adult↗
Prognostic value of serum lactic dehydrogenase (S-LDH) in multiple myeloma.
Serum lactic dehydrogenase (S-LDH) was analysed at diagnosis in ninety-three patients with multiple myeloma. The patients were then followed up after a mean observation period of 39 months (SD 29). Serum lactic dehydrogenase was elevated in twenty-seven out of ninety-three patients and found to correlate with the serum concentrations of beta 2-microglobuline, creatinine, and thymidine kinase. In discriminant analysis of pretreatment S-LDH levels in relation to survival, the best discrimination level was 7.0 mukat 1(-1). Patients with values below 7 microkat 1(-1) ahd a median survival time of 45 months compared to 14 months for those with levels above 7 mukat 1(-1) (P less than 0.001). Serum lactic dehydrogenase at diagnosis, thus, has prognostic information in multiple myeloma.
Humans↗
Pretreatment serum beta 2-microglobulin in multiple myeloma.
Serum beta 2-microglobuline (S-beta 2m) was evaluated in 121 untreated patients with multiple myeloma. Values greater than 3 mg/l were found in 82% of the patients. Mean S-beta 2m values of the total group of patients correlated with clinical stage. However, there was no correlation if values were corrected for S-creatinine. Seventy-nine patients had normal (less than or equal to 106 mumol/l) and 52 patients abnormal S-creatinine. Patients with S-beta 2m values below 7 X 6 mg/l had an estimated median survival of 44 months compared to 12 months for patients with levels above 7 X 6 mg/l. If S-beta 2m values in patients with normal S-creatinine were combined with values corrected for S-creatinine from patients with elevated S-creatinine a beta 2m cut off level of 6 X 6 mg/l gave a median probable survival of 43 months compared to 14 months. We conclude that pretreatment S-beta 2 microglobulin is a useful marker for predicting survival in multiple myeloma. The problem of the relationship between S-beta 2m and S-creatinine is discussed.
Adult↗
The effect of alpha and gamma-interferon on proliferation and production of IgE and beta 2-microglobulin in the human myeloma cell line U-266 and in an alpha-interferon resistant U-266 subline.
An IFN-resistant subline (U-266r alpha) was established from the IFN-alpha-sensitive myeloma cell line U-266 by subculturing U-266 cells with increasing doses of INF-alpha. The U-266r alpha secreted IgE at a higher rate than the U-266 (7.2 X 10(-13) g/c/8 h as compared to 3.3 X 10(-13) g/c/8 h). The 2 cell lines were found to be equally high producers of beta 2m (9.2 and 9.6 X 10(-13) g/c/8 h). The U-266 produced 2.9 times less IgE and 5 times more beta 2m compared to the initial production rates at establishment. INF-alpha and recombinant IFN-alpha 2 (rIFN-alpha 2) inhibited proliferation and concomitantly decreased the rate of IgE and beta 2m secretion in U-266 but not in U-266 IFNr alpha, which in contrast was slightly stimulated by IFN-alpha with respect to growth, IgE and beta 2m secretion. In addition, IFN-alpha at a concentration of 100 U/ml was shown to decrease the IgE and beta 2m production without exerting more than minimal cytotoxicity on U-266 cells. No antiproliferative effect was found for IFN-gamma or recombinant IFN-gamma (rIFN-gamma) on either of the 2 cell lines. IFN-gamma and rIFN-gamma were, however, found to stimulate the production of beta 2m. Our results show that the U-266 and the derived IFN-alpha-resistant subline can be used as models for studying some of the biological effects of IFN-alpha and -gamma in vitro. The clinical implications of these in vitro results, in particular the usefulness of serum determinations of immunoglobulin and beta 2m concentrations for monitoring the tumor cell mass, are discussed.
Cell Division↗
Evaluation of serum deoxythymidine kinase as a marker in multiple myeloma.
A recently developed deoxythymidine kinase assay utilizing 125I-iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S-TK), although in some patients values increased by more than forty-fold were found. S-TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, beta 2-micro-globulin, Ca or M-component. The distribution of S-TK values in IgG, IgA and pure Bence-Jones myeloma did not differ significantly. Patients with IgG and IgA myeloma excreting light-chain immunoglobulin in the urine had significantly higher S-TK than non-excreters. There was a significant correlation between S-TK values and tumour cell mass as determined by clinical staging. A high pretreatment S-TK (greater than 5.1 units) also distinguished a group of patients with a significantly shorter survival time. Patients with no response to initial therapy had significantly higher S-TK values than those who did respond. In longitudinal studies of 11 patients, S-TK was found to increase when the disease became more aggressive. The possibility of diagnosing disease progression at an early stage by an elevation of S-TK is discussed.
Adult↗
Serum beta 2-microglobulin at remission and relapse in patients with multiple myeloma.
Serum beta 2-microglobulin (S-beta 2m) was determined before treatment in fifty patients with multiple myeloma (MM), twenty-two of which had pure Bence Jones (BJ) myeloma. S-beta 2m was related to clinical stage before, but not after, a correction of S-beta 2m values for co-existent raised S-creatinine values (greater than 106 mumol 1-1). However, S-beta 2m as well as corrected beta 2m was a parameter of prognostic value. The median expected survival time was 14 months at S-beta 2m values greater than 8.0 mg 1(-1) and 56 months at values less than 3.5 mg 1(-1). A response to treatment was associated with a decrease of S-beta 2m and a stationary course with unchanged values, whereas a relapse or progressive disease was connected with an increase. In 'beta 2m producers', i.e. patients with a clear initial high S-beta 2m, serial determinations are of value for monitoring patients with MM. In particular, this is the case in BJ myelomas, as they lack a quantifiable serum M-component. With respect to beta 2m no difference was found between BJ and other patients with MM.
Adult↗
The in vitro effect of leucocyte alpha-interferon on human myeloma cells in a semisolid agar culture system.
73 bone marrow samples from a total of 50 patients with multiple myeloma (MM) were tested for interferon (IFN) sensitivity in the human tumour colony assay (HTCA). 16 evaluable samples were obtained from untreated patients, 10 from patients during melphalan and prednisone treatment and 6 from patients on IFN treatment or after withdrawal of IFN. The sensitivity to IFN was individually distributed between the bone marrow samples from patients of all 3 groups and a tendency towards IFN resistance could be found in serial assays from patients during MP-treatment and after IFN withdrawal. Stimulation of growth was found in 31% of the cultures, usually at lower doses of IFN (10-100 U/ml) while higher doses (400-4000 U/ml) inhibited growth in 75% of the assays.
Agar↗
Correlation between in vitro and in vivo sensitivity to human leucocyte interferon in patients with multiple myeloma.
26 of 32 patients with multiple myeloma (MM) were successfully tested in vitro for human leucocyte interferon (IFN) sensitivity by use of the human tumour stem cell assay (HTCA) and/or 3H-thymidine incorporation (LI). Altogether, 12 patients were sensitive to IFN in vitro and 14 were resistant. All patients received treatment with leucocyte IFN. 8 patients were classified as responders, 3 as partial responders and 15 as non-responders. Correlating the in vitro/in vivo results, we found that the in vitro tests of the myeloma cells reflected a true sensitivity in 9 patients (75%) and a true resistance in 12 patients (86%). Furthermore, stimulation by IFN was found in 9 in vitro tests, of which 8 were obtained from non-responsive patients. Our results show that in vitro testing for IFN sensitivity is of clinical importance in predicting response to IFN treatment. Also, a stimulating effect by IFN in vitro will imply an unfavourable response in vivo.
Adult↗