Search PubMed⌕ Search

Biomedical subjects

J Westin

Publications and source records attributed to J Westin.

At least 55 records · Page 3Linked to original sources

Serum deoxythymidine kinase: no help in the diagnosis and prognosis of monoclonal gammopathy.

Serum deoxythymidine kinase activity (S-TK) was determined in the diagnostic evaluation and follow-up of patients with monoclonal gammopathy of undetermined significance (MGUS). During a 4-year period 35 patients were included in the study. Normal concentrations of S-TK were found in 33. Patients with non-progressive monoclonal gammopathy kept a stable, and for the individual, a characteristic level of S-TK during several years of follow-up. A moderately elevated level of S-TK during observation did not indicate progression. Even in four out of five patients developing symptomatic multiple myeloma S-TK remained unchanged. Determination of S-TK does not give diagnostic or prognostic information in monoclonal gammopathy.

Aged↗

Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Myeloma Group of Western Sweden.

From October 1983 until December 1988, 50 patients with asymptomatic multiple myeloma stage I were included in a prospective randomized multi-centre study comparing melphalan-prednisone (MP) therapy started at the time of diagnosis with deferred therapy where MP was started at the time of disease progression. Twenty-five patients were randomized to each group. The median time from diagnosis to start of therapy in the group with deferred therapy was 12 months. The reasons for starting therapy were increasing M-protein in 8 cases, symptomatic bone disease in 9 and anaemia in 5. In 2 cases, disease progression was complicated by vertebral fractures necessitating radiotherapy. Two patients in the group in which MP was started at the time of diagnosis developed acute leukaemia. No differences in response rate, response duration or survival were observed between the treatment groups. We conclude that in asymptomatic myeloma deferral of chemotherapy is feasible in well-informed and well-controlled patients but conveys no advantage in survival. In clinical practice the benefits of treatment deferral are to some extent outweighed by disease progression before start of treatment.

Adult↗

Impact of active and passive exclusions on the results of a clinical trial in multiple myeloma. The Myeloma Group of Western Sweden.

During the 3 years 1984-86, 314 cases of multiple myeloma were diagnosed in the Health Care Region of Western Sweden. 180 of these cases were included in a clinical trial; 71 were notified to the trial but excluded; 49 cases were not reported to the trial; 14 were diagnosed post mortem. The crude incidence rate of myeloma was 6.3 cases per 100,000 inhabitants per year, corresponding to an age-adjusted (world standard population) incidence rate of 2.9 cases per 100,000 inhabitants per year. The excluded and the non-reported patients had a significantly shorter survival than those included in the clinical trial (median survival 22, 13 and 33 months, respectively). This was partly due to differences in age and proportion of actively treated patients between the groups, but the same tendency remained also after correction for these factors. Considering the included patients separately, the effect of tentative application of presumptive exclusion criteria corresponding to major prognostic factors was studied. Prolonged survival was seen when the upper age limit was lowered and when patients with renal failure or low performance status were excluded. The results illustrate the fact that for multiple myeloma the survival in a trial population is markedly influenced by active and passive exclusion of patient groups with unfavourable prognostic characteristics. When reporting results of clinical trials, discussion of the representativeness of the trial population for the total patient population is recommended in order to facilitate application of the trial results to medical practice and comparisons between trials.

Adult↗

Bolus therapy with mitoxantrone and vincristine in combination with high-dose prednisone (NOP-bolus) in resistant multiple myeloma. Nordic Myeloma Study Group (NMSG).

In a phase II study, 58 patients with resistant multiple myeloma (MM) were treated with a combination chemotherapy (NOP-bolus regimen) consisting of mitoxantrone (16 mg/m2 for the first 25 patients and 12 mg/m2 for the subsequent 33), vincristine (2 mg), both as bolus injections on day 1 and prednisone (250 mg/d on d 1-4 and 17-20). In patients greater than 70 years of age, the mitoxantrone dose was reduced to 12 mg/m2 or 8 mg/m2, respectively. The treatment was repeated every 4 weeks. A response (greater than 50% reduction in M component) was obtained in 26% of the patients and a minor response (clinical improvement but less than 50% reduction in M component) in another 21%. Median response duration was 27 wk and median survival for all patients was 25 wk. There were no differences in response rate or duration between patients receiving the high or low mitoxantrone dose, but patients in the low-dose group had fewer serious infections.

Adult↗

The effect of alpha-interferon on bone marrow megakaryocytes and platelet production rate in essential thrombocythemia.

In 10 patients with previously untreated essential thrombocythemia (ET), by using 111In-labeled platelets and megakaryocyte morphometry, the relation between platelet production rate and bone marrow megakaryocytes was evaluated before and during alpha-2b-interferon (IFN) therapy. A highly significant decrease in platelet count occurred during IFN therapy; the platelet counts, at baseline and after 2 and 6 months of IFN therapy, were 1,102 +/- 345 x 10(9)/L, 524 +/- 169 x 10(9)/L (P less than .0001), and 476 +/- 139 x 10(9)/L (P less than .0001), respectively. The decrement in platelet count was mainly a result of diminished platelet production rate, which at baseline and after 2 and 6 months of IFN therapy was 89 +/- 30 x 10(10) platelets/d, 53 +/- 18 x 10(10) platelets/d (P = .0033), and 45 +/- 20 x 10(10) platelets/d (P less than .0001), respectively. Also, a slight shortening of platelet mean life-span (MLS) was observed in response to IFN treatment; platelet MLS was 7.96 +/- 0.69 days at baseline and 6.68 +/- 1.30 days (P = .012) after 6 months of IFN therapy. IFN induced a significant decrease in bone marrow megakaryocyte volume; both megakaryocyte nuclear and cytoplasmatic volumes were affected. The mean megakaryocyte volume was 372 +/- 126 x 10(2) pL/microL at baseline and 278 +/- 147 x 10(2) pL/microL (P = .049) after 6 months of IFN therapy. However, the number of megakaryocytes did not show any significant change in response to IFN. It is concluded that alpha-IFN reduces platelet production rate and the peripheral platelet count in ET mainly through an anti-proliferative action on the megakaryocytes and to a considerably lesser degree by a shortening of platelet MLS.

Adult↗

Interferon therapy during the plateau phase of multiple myeloma: an update of the Swedish study.

A multicentre clinical trial was carried out in order to evaluate the effect of interferon (IFN) in patients with multiple myeloma. Patients (n = 120) who had shown response to conventional intermittent melphalan-prednisone induction therapy, and achieved a plateau phase, were randomized at that point to receive either interferon alfa-2b in a dose of 5 million units (MU) three times per week or no therapy. This report presents the results of an interim analysis, performed when the patients had been followed for a median of 20 months. The duration of the plateau phase was significantly longer in the IFN arm (59 weeks), compared to the no therapy arm (26 weeks). A total of 34 deaths have occurred, 13 in the IFN arm and 21 in the no therapy arm. In spite of the high median age of the patients studied (70 years), most patients were able to tolerate a full or only slightly reduced IFN dose.

Aged↗

Serum cobalamins in the elderly: a longitudinal study of a representative population sample from age 70 to 81.

In a representative population sample (n = 973) born 1901-1902 and examined at the ages of 70, 75, 79, and 81, the change in serum cobalamins with increasing age was studied by trend analysis using values obtained in single individuals at all four examinations. In subsamples without definable disorders, the mean annual decline was: among men 3.4 pmol/l (p less than 0.05), among women 3.2 pmol/l (n.s.). The decline was possibly more pronounced among individuals with low and intermediate concentrations. The health-related lower reference limits (the 2.5 percentile values of subsamples without definable disorders) did not differ significantly between sexes and age groups, but low concentrations or ongoing cobalamin medication became more common with advancing age. The results indicate a slight fall in serum cobalamins between age 70 and 81 but do not call for age-related lower reference limits.

Aged↗

Comparison of methods for the biomonitoring of nurses handling antitumor drugs.

Urinary mutagenicity, thioethers in urine, and sister chromatid exchanges and micronuclei in peripheral lymphocytes were determined for 60 nurses handling cytostatic drugs and 60 referents matched for sex, age, and smoking habits. Safety hoods were used by most of the nurses. The exposed nurses had more sister chromatid exchanges and higher urinary mutagenicity, as measured by Salmonella typhimurium TA 98, than the referents. There were no differences in the other tests. No dose-response relationship was established for any parameter. It was concluded that urinary mutagenicity with the Salmonella strain is the most sensitive test for monitoring nurses handling cytostatic drugs. Determining sister chromatid exchanges may also be a viable test, but it has the drawback of uncertainty as to whether the changes are attributable to present or past exposure. Only comparisons of rather large groups are useful, and a study design requiring matched referents would seem to be optimal.

Adult↗

Interferon therapy during the plateau phase of multiple myeloma: an update of a Swedish multicenter study.

Over the course of a 2-year period (September 1987 to September 1989) a total of 432 patients with multiple myeloma were registered in a study comprising 39 Swedish and one Italian clinics. Six of these were university hospitals, the others were county (community) hospitals. A total of 308 patients fulfilled the eligibility criteria of the protocol, and were started on traditional intermittent melphalan-prednisone therapy. Response, defined as a reduction in the concentration of the M-component in serum or urine, was observed in 58% of patients, and a clearly defined plateau phase was noted in 38% of the cases. Of the patients who achieved a plateau phase, 120 individuals (with a median age of 71 years) were at this point randomized between no further therapy and continuous interferon-alfa-2b at a dose of 5 x 10(6) IU subcutaneously three times per week. At relapse the interferon therapy was discontinued, and melphalan-prednisone restarted. Only preliminary data and interim results are at this point available. The final evaluation of the study will be performed after June 1, 1991. The treatment arms are comparable with regard to age, stage according to Durie-Salmon, renal function, immunoglobulin class, and type of response to the cytostatic therapy (rapid versus slow). A median number of six courses of melphalan-prednisone were administered before randomization. For those patients in whom pretreatment serum beta-2-microglobulin was analyzed, no difference in the median values between the treatment arms was found. The median observation time from randomization is 20 months. At the time of this analysis, 85 had relapsed: 33 of 59 (56%) in the interferon arm, and 52 of 61 (85%) in the no therapy arm. An interim analysis of the duration of the plateau phase (from the time of randomization) was performed in October 1990, showing a highly significant difference between the two treatment arms (P less than .001). The median duration of plateau was 59 weeks in the interferon arm, and 26 weeks in the no therapy arm. To date there have been 34 deaths, 13 in the interferon arm and 21 in the no therapy arm. All patients in the no therapy arm died from multiple myeloma (n = 19), or from another cause, but with the myeloma in an uncontrolled, progressive state (n = 2). In the interferon arm, only 10 patients died from progressive myeloma, and four of these either did not start interferon therapy at all (n = 1), or discontinued therapy early (n = 3).(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

[Paroxysmal nocturnal hemoglobinuria, a cell surface molecular defect].

Paroxysmal nocturnal haemoglobinuria is an acquired haemolytic anaemia that may develop into aplastic anaemia or myeloid leukaemia. It has recently been shown that paroxysmal nocturnal haemoglobinuria is due to a defective coupling of specific proteins to glycolipids on the cell surface of haematopoietic cells. One of these proteins is decay-accelerating factor (DAF), and the absence of DAF on the surfaces of blood cells leads to the haemolytic symptoms. The molecular biology of DAF and its relationship to paroxysmal nocturnal haemoglobinuria symptoms is described in this brief review. The molecular defect of paroxysmal nocturnal haemoglobinuria is illustrated in a case report.

Adult↗

Cytogenetic abnormalities in acute leukemia complicating melphalan-treated multiple myeloma.

The cytogenetic findings in 11 patients with multiple myeloma in whom a myelodysplastic syndrome or an acute nonlymphocytic leukemia developed are reported. All patients were treated with oral melphalan for 2-9 years in a total dose of 0.5-4.1 g. When examined during the myelodysplastic or leukemic phase, all patients had an abnormal bone marrow karyotype, hypodiploid in nine of the 11 cases. The chromosome abnormalities were clearly nonrandom and comprised a 5q deletion in three cases, monosomy 5 in four cases, deletion 7q--in two cases, and monosomy 7 in three cases. Loss of material from the long arm of chromosomes 5, 7, or both was found in eight patients. The different chromosome abnormalities were not associated with any specific morphological or clinical features.

Aged↗

Bone marrow in vitro growth and cytogenetic studies in patients with FAB-classified primary myelodysplastic syndromes.

Thirty-eight consecutive patients with a FAB-classified primary myelodysplastic syndrome (MDS) were investigated for in vitro growth of colony-forming units for granulocyte-macrophage precursors (CFU-GM) and cytogenetic analysis of bone marrow cells. Abnormal CFU-GM growth was found in 30 patients (79%), and clonal chromosome abnormalities were found in 13 patients (34%). The eight patients who showed normal CFU-GM growth were either cytogenetically normal (n = 5), or had a 5q-deletion (n = 3) as single or dominating karyotypic abnormality. Among the 30 patients with reduced or no colony growth, ten patients had a clonal chromosome abnormality. Leukemia developed in eight patients. None of them grew any CFU-GM colonies, and three of them were cytogenetically abnormal at the time of diagnosis of MDS. Analysis of the bone marrow in vitro growth for CFU-GM and the karyotype in patients with MDS emphasizes the close relationship between these disorders and manifest acute leukemia. Subgroups of MDS may be defined by a cytogenetic classification (e.g., the 5q-syndrome), and the CFU-GM growth pattern can be of value for predicting leukemic transformation.

Aged↗

Initial treatment in multiple myeloma: no advantage of multidrug chemotherapy over melphalan-prednisone. The Myeloma Group of Western Sweden.

From October 1983 until December 1986, 164 patients with multiple myeloma stage II-III were included in a prospective randomized multi-centre study comparing melphalan-prednisone (MP) with multidrug chemotherapy (MDC). The patients comprised 77% of all newly diagnosed myeloma stage II-III cases reported from 18 hospitals covering the entire Health Care Region of Western Sweden (1.5 million inhabitants). Patients randomized to MP (29 stage II and 55 stage III patients) were given oral melphalan and prednisone every 6 weeks. For patients randomized to MDC, stage II patients (n = 25) were given VMCP every 4 weeks and stage III patients (n = 53) VBAP and VMCP alternately every 4 weeks. For stage II patients, the response rate for MP compared to VMCP was 69 versus 56% and the median survival 46 versus 33 months. For stage III the response rate for MP compared to VBAP/VMCP was 58 versus 57% and the median survival 26 versus 24 months. No statistically significant differences were seen. The time to response and remission duration were also similar in both treatment arms. The dose intensity index (cumulative given/planned dose of myelosuppressive drugs) was greater than or equal to 0.8 in 89% of the MP patients and 81% of the MDC patients. Patients with index values less than 0.8 had the same response rate as patients with index greater than or equal to 0.8. This study has not demonstrated any advantage of MDC over traditional MP in multiple myeloma stage II-III.

Adult↗

Effect of interferon alpha-2b in advanced multiple myeloma.

The antitumour effect of recombinant human interferon (rh-IFN) alpha-2b was studied in 22 patients with advanced multiple myeloma (MM). Nine of 14 evaluable cases were refractory to cytostatic therapy; five were in relapse. rh-IFN was administered s.c. three times per week, in escalating doses starting with 2 x 10(6) IU m-2 and if possible up to 15 x 10(6) IU m-2. Two patients (one refractory, one relapsing) showed a partial response, defined as a 50% reduction of the serum M-component. Three further patients had a minor, significant but short-lived response. Subjective side-effects grade 1-2 were noted during rh-IFN therapy in all patients. In three cases thrombocytopenia necessitating platelet transfusions occurred. Although a fraction of patients with advanced MM obviously respond to rh-IFN, this type of therapy may be more effective, alone or in addition to chemotherapy, in patients with a low tumour cell burden.

Aged↗

Single-dose intravenous melphalan in advanced multiple myeloma.

Eight patients with progressive multiple myeloma were given an intermediate intravenous dose of melphalan (30 mg/m2). A response lasting 2-18 months was observed in 7 patients. The bone marrow toxicity was well acceptable and most courses could be given on an outpatient basis. Intermediate-dose intravenous melphalan may be considered an alternative for treatment of relapsing or progressive multiple myeloma, even if the patient has previously received oral melphalan.

Drug Administration Schedule↗