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D E Bergsagel

Publications and source records attributed to D E Bergsagel.

At least 19 recordsLinked to original sources
PubMed1995

The role of chemotherapy in the treatment of multiple myeloma.

Plasma cell neoplasms often present in an asymptomatic, stable phase. Treatment should not be started until manifestations, such as bone pain, increased susceptibility to infections, renal failure, anaemia and weight loss, announce that the disease has progressed to the MM phase. Conventional therapy with melphalan and prednisone results in objective improvement in about 50% of patients and improves median survival to about 32 months from the start of treatment. Induction therapy should be continued until the M-protein reaches a stable plateau that lasts for at least 4 months. Maintenance therapy with melphalan prolongs the duration of the initial response, but does not improve overall survival, in comparison with patients receiving no maintenance therapy, because survival following relapse is shortened in those receiving maintenance melphalan. In two randomized clinical trials, maintenance treatment with interferon alpha prolonged remissions durations and overall survival of MM patients who responded to induction chemotherapy. Second-line treatment for MM patients who are primary refractory to melphalan, and for those who respond initially and then relapse with refractory disease, is outlined. Although long-term control is possible for a minority of patients, it is unlikely that MM can be cured with currently available chemotherapeutic agents. We need to learn more about the basic biology of the disease.

Antineoplastic Agents↗
PubMed1994

Determination of IL6, IL1, and IL4 in the plasma of patients with multiple myeloma.

Interleukin 6 (IL6) plasma levels were measured in 63 patients with multiple myeloma and 8 individuals with benign monoclonal gammopathy. 15 of these 71 samples showed by an enzyme linked immunosorbent assay (ELISA) detectable levels that ranged from 5 to 107 pg of IL6/ml. The IL6 levels of patients with multiple myeloma did not differ significantly from those of normal individuals (N = 25, range 5-27 pg IL6/ml) (Student's t-test, p = 0.295). The samples were negative for IL4; 3 were found positive for IL1 beta. A correlation between IL6, IL4 and IL1 beta levels and disease status was not observed for this group of patients.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Analysis of supradiaphragmatic clinical stage I and II Hodgkin's disease treated with radiation alone.

Patients with clinical Stage I and II Hodgkin's disease have been managed at the Princess Margaret Hospital for over 20 years, without the use of routine staging laparotomy. Our experience identified as adverse prognostic factors presence of a large mediastinal mass, B symptoms, and advanced age in presence of unfavorable histology (20). We had suggested previously that the use of extended field radiation therapy (XRT) was associated with a lower risk of relapse than involved field XRT or mantle XRT. There has been a trend over the past decade to select those patients with favorable prognostic factors for treatment with XRT alone and to use mantle plus upper abdominal XRT (extended field XRT) to treat them. A retrospective study of patients with clinical Stage I and II Hodgkin's disease treated at the Princess Margaret Hospital between 1978 and 1986 was conducted to determine the impact of patient selection and extended field radiation on outcome. The study involved 250 patients with supradiaphragmatic disease selected for treatment with radiation alone on the absence of adverse prognostic factors. Radiation techniques included involved field radiation in selected patients (those with upper neck involvement), mantle radiation in the earlier years, and mantle plus upper abdominal radiation in the later years of the study. Actuarial survival was 83.3% at 8 years; cause-specific survival was 90.1% and the relapse-free rate 71.6%. Local tumor control was 94.6%; only two patients had true infield failure. Multivariate analysis showed that significant prognostic factors included age, histology, and erythrocyte sedimentation rate. Extent of the radiation treatment volume was significant and influenced the risk of relapse, particularly out-of-field relapse, independently of other factors. A dose of 35 Gy was found to be sufficient for control of clinical disease. This study validated a previously developed model for the selection of clinically staged patients with Stage I and II Hodgkin's disease for treatment with radiation alone. Careful selection of these patients can yield excellent results without requiring that staging laparotomy be routinely performed or the use of systemic chemotherapy as the initial treatment.

Adolescent↗
PubMed1992

Radiation therapy in clinical stage I and II Hodgkin's disease. The Princess Margaret Hospital Lymphoma Group.

A review of the Princess Margaret Hospital experience over the last 20 years in treating clinically staged patients with stage I and II Hodgkin's disease was performed to analyse the impact of patient selection and extended field radiation on relapse and survival. Of the 878 patients with stage I and II Hodgkin's disease, 521 with clinical stages I and II received radiation alone as the initial treatment. The actuarial survival for all stage I and II patients was 85.1% at 5 years and 76.2% at 10 years, and for clinically staged patients treated with radiation alone, 87.2 and 77.6%, respectively. The relapse-free rate (RFR) for all clinical stage I and II patients treated with radiotherapy (RT) alone was 70.1% at 5 years and 65.8% at 10 years. Significant prognostic factors for RFR and survival included age, stage and histology. In addition, the extent of radiation was identified as an independent prognostic factor for survival as well as for relapse. The RFR for those treated with involved field RT was 58.4% at 5 years and 50.5% at 10 years; for patients treated with mantle RT, 69.9 and 65.6%, and those treated with extended field RT 77.4 and 75.8%, respectively. In a highly selected group of patients with no adverse features, i.e. with stages IA-IIA, lymphocyte predominant or nodular sclerosis histology, erythrocyte sedimentation rate < 40, age < 50, no large mediastinal mass, and no E-lesions--the policy of mantle RT (M) and extended field RT (EF) produced comparable 5-year relapse-free rates (M, 84.9%; EF, 87.1%; P = 0.53). We conclude that a policy of treatment selection based upon clinicopathological prognostic factors and the use of extended field RT confers excellent results in the treatment of clinical stage I and II Hodgkin's disease.

Adolescent↗
PubMed1991

Plasma cell myeloma: biology and treatment.

Plasma cell myeloma results from malignant transformation in an early hemopoietic precursor cell. The disease progresses from an asymptomatic stable phase through a symptomatic phase to a terminal acute phase marked by aggressive cell growth and marrow failure. The activation of a series of oncogenes may govern the initiation and stepwise progression of these neoplasms. Chemotherapy causes the tumor to regress in about 50% of patients and improves survival, but it does not alter the course of the disease. Interferon maintenance therapy prolongs remission durations and appears to alter the course of the disease.

Cell Transformation, Neoplastic↗
PubMed1991

Effect of daily etidronate on the osteolysis of multiple myeloma.

Progressive bone disease in multiple myeloma frequently leads to osteolysis, bone resorption, pathologic fractures, vertebral compression, and hypercalcemia. We conducted a double-blind study in 173 newly diagnosed multiple myeloma patients of etidronate disodium (EHDP), a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned to receive oral EHDP 5 mg/kg/d or placebo until death or discontinuation due to intolerance or refusal. The extent of vertebral deformity was measured by a vertebral index as well as height. The frequency of pathologic fractures, hypercalcemia, and bone pain was regularly assessed, as well as size and number of osteolytic lesions. All patients received melphalan and prednisone daily for 4 days every 4 weeks as the primary chemotherapy for their disease. Although the repeated measures analysis showed a significant height loss, there was no difference between treatment arms (P = .98). There was no significant difference in bone pain, episodes of hypercalcemia, or development of pathologic fractures. Patients on EHDP showed less deterioration in their vertebral index, but this difference only approached statistical significance (P = .07). We conclude that EHDP therapy used in this dosage schedule does not have a clinically significant impact in multiple myeloma.

Aged↗
PubMed1990

The maintenance of busulphan-induced remissions in chronic granulocytic leukaemia with recombinant interferon alpha-2b.

Interferon (IFN) shows no specificity in inhibiting the growth of colonies of myeloid leukaemia blasts in culture as compared to normal haemopoietic precursors, but does reduce the self-renewal capacity of myeloblasts. We have tested the ability of IFN to slow the leukocyte doubling time (Ldt) and to prolong remissions induced by busulphan in 14 patients with chronic granulocytic leukaemia (CGL). Patients served as their own controls; the Ldt during relapse from a busulphan-induced remission on no therapy was determined and compared with the Ldt on IFN maintenance therapy. The initial dose of IFN (2 x 10(6) U M-2 subcutaneously, three times per week) was adjusted up, or down, to prevent the leukocyte count from rising and the platelet count from falling below 75 x 10(9) l-1. The dose of IFN required to prevent relapse in seven patients ranged from 1 x 10(6) U M-2 three times per week to 5.2 x 10(6) U M-2 daily, with a median of 2 x 10(6) U M-2 three times per week. IFN maintenance therapy has prevented relapse in six patients for more than 22 months to more than 68 months. In five patients the Ldt was slowed initially but the disease later progressed in four patients to enter the accelerated (three patients) or blast phase (one patient). The Ldt during IFN therapy did not change from the Ldt on no therapy in one patient; this patient later progressed to the blast phase. In two additional patients the leukaemia progressed during the first course of IFN, with shortening of the Ldt; both of these patients entered the blast phase. In the four patients who have discontinued IFN following relapse in the chronic phase, the Ldt remained prolonged for at least one relapse after the IFN was stopped. IFN maintenance therapy failed to control the leukocyte count in the six patients with a control Ldt of less than 40 days and five of these have progressed to enter the accelerated or blast phase. The early survival of this group of patients resembles the survival of 'good risk' CGL patients reported by others. We conclude that IFN maintenance therapy does alter the relapse pattern of a subset of CGL patients, either slowing the Ldt or preventing relapse.

Adult↗
PubMed1989

Melphalan/prednisone versus drug combinations for plasma cell myeloma.

Reports of 13 prospective, randomized clinical trials comparing standard treatment with melphalan and prednisone (MP) versus various drug combinations in the treatment of myeloma patients are presented. These studies reveal that patients with Durie-Salmon Stage III disease respond significantly more frequently to MP and drug combinations than those with Stage I and II. Drug combinations may be more effective in inducing objective responses. The response rates were significantly better for the drug combinations in 3 of the 13 comparisons. There was little evidence that either form of treatment was superior in prolonging survival, for in one study the patients treated with a drug combination lived significantly longer than those treated with MP, while in another the reverse was true, and there was no difference in the survival of the two groups in the remaining 11 studies. In the Vth MRC myelomatosis trial, patients treated with a combination of adriamycin, carmustine, cyclophosphamide and melphalan are living significantly longer than those treated with melphalan alone, and this survival advantage persists after correction for the most important prognostic factor, beta 2 microglobulin. Attempts to increase the intensity of treatment by using syngeneic, allogeneic or autologous marrow transplantation to rescue patients following otherwise lethal chemoradiotherapeutic treatments, have not yet demonstrated conclusively that the myeloma clone can be eliminated by this form of treatment.

Antineoplastic Combined Chemotherapy Protocols↗