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Biomedical subjects

M A Dimopoulos

Publications and source records attributed to M A Dimopoulos.

At least 163 records · Page 9Linked to original sources

Primary dexamethasone treatment of multiple myeloma.

Intermittent courses of dexamethasone (DEX) were administered to 112 consecutive, previously untreated patients with multiple myeloma (MM). Using criteria based on a 75% or greater reduction of calculated tumor mass, the overall response rate was 43%. Among comparable patients, response rate were approximately 15% less than those observed previously with vincristine-doxorubicin by continuous infusion with intermittent DEX (VAD) and similar to those with melphalan-prednisone. The projected survival times with VAD or DEX were similar. Results indicated that DEX accounted for most of the plasma cell reduction achieved with VAD. Serious complications occurred in 27% of patients treated with VAD, but in only 4% of those who received DEX. In view of the similar outcome with fewer serious complications, DEX provided a simple, effective, and safe primary treatment for a large fraction of patients with MM. Patients who appear most likely to benefit include those with hypercalcemia or pancytopenia, or who require simultaneous radiotherapy for a pathologic fracture.

Adult↗

Paraneoplastic Cushing's syndrome as an adverse prognostic factor in patients who die early with small cell lung cancer.

The potential role of paraneoplastic Cushing's syndrome (CS) was assessed on the clinical course of patients with small cell lung cancer. A retrospective comparison was done of complications and survival rates according to the presence or absence of CS in patients with small cell lung cancer who died within 90 days of initial administration of chemotherapy. The setting was a comprehensive cancer center. Eleven patients with clinical and/or biochemical features of CS were identified from among 90 patients who presented between 1979 and 1989 with previously untreated small cell lung cancer. The group with CS and the control patients were compared in terms of clinicopathologic prognostic factors, treatment, and outcome. Patients with CS were comparable to the control patients in all prognostic factors, including tumor stage and cancer treatment. Eighty-two percent of patients with CS (nine of 11) died within 14 days of initiation of chemotherapy compared with 25% of the control patients (19 of 77). The median survival from initiation of chemotherapy was 12 days for the 11 patients with CS and 27 days for the 77 control patients. In 45% of the patients with CS (five of 11), death was attributed to opportunistic fungal or protozoal infection compared with 8% of control patients (six of 77). Paraneoplastic CS is a previously unrecognized adverse prognostic factor for patients with small cell lung cancer. Those with both small cell lung cancer and CS have severe opportunistic infections soon after the initiation of chemotherapy, leading to clinical deterioration and death before antineoplastic benefit from chemotherapy can be achieved. Biochemical control of CS for at least 1 to 2 weeks before initiation of chemotherapy may ameliorate the poor prognosis.

Adult↗

Multiple myeloma: spinal MR imaging in patients with untreated newly diagnosed disease.

Spinal magnetic resonance (MR) imaging was performed in 29 patients with newly diagnosed, untreated multiple myeloma. Nineteen (66%) patients were asymptomatic. Sagittal pre- and postcontrast T1-weighted spin-echo images and gradient-recalled-echo images of the thoracic and lumbosacral spine were obtained. Marrow involvement was identified in 20 (69%) patients. There were three MR patterns: focal lesions in nine patients (31%), diffuse involvement in seven (24%), and an inhomogeneous pattern of tiny lesions on a background of normal marrow in four (14%). A statistically significant correlation between MR imaging patterns of marrow involvement and serum hemoglobin values (one-way, P = .0899; Kruskal-Wallis, P = .0620) and between MR imaging patterns and percentage of marrow plasmacytosis (Kruskal-Wallis, P = .0314) was noted, with patterns of diffuse and focal marrow involvement associated with more abnormal values. Spinal MR imaging in patients with early myeloma may reveal marrow involvement in both symptomatic and asymptomatic patients. Some correlation was found between MR imaging patterns and laboratory indexes of disease.

Adult↗

Curability of solitary bone plasmacytoma.

PURPOSE: The effects of involved-field radiotherapy were assessed in patients with a solitary plasmacytoma of bone (SBP). PATIENTS AND METHODS: Forty-five consecutive patients with an SBP received megavoltage irradiation of at least 3,000 cGy. The median age was 53 years, 67% of patients showed a myeloma protein, and uninvolved immunoglobulins (Igs) were preserved in 93% of patients. RESULTS: Permanent control of presenting disease was achieved in all but two patients, but 46% of patients developed multiple myeloma. When it occurred, progression of myeloma occurred within 3 years in two thirds of the patients, suggesting that the extent of disease was understaged at diagnosis. Myeloma protein disappeared in nine patients (30%) whose disease has not yet recurred. The median survival for all patients was 13 years and the myeloma-specific survival fraction at 10 years was 53%. CONCLUSION: In patients with an SBP, the disappearance of myeloma protein with involved-field radiotherapy predicted long-term disease-free survival and possible cure. Nonsecretory disease and persistent myeloma protein after treatment were adverse prognostic factors for which adjuvant therapy with interferon alfa should be considered.

Adult↗

Solitary plasmacytoma of bone and asymptomatic multiple myeloma.

There is a wide spectrum of disease among patients with plasma cell myeloma. A small fraction have a localized plasmacytoma of bone that requires specialized techniques for accurate staging, followed by local radiotherapy that may be curative in some patients. Other patients with multiple myeloma may be free of symptoms and the disease is recognized by chance laboratory studies. Some have a prolonged, stable course with little change in disease for many months or years and resemble patients with MGUS. These patients have low serum myeloma protein and are free of focal bone lesions even on MR imaging. Complications are more imminent among other patients with higher levels of myeloma protein and/or bone lesions, who usually require treatment within 2 years after diagnosis. Still other patients with more advanced generalized disease (intermediate tumor mass) or with a pathologic fracture that may be relieved with local radiotherapy usually require even earlier chemotherapy to prevent or treat complications.

Bone Neoplasms↗

High serum lactate dehydrogenase level as a marker for drug resistance and short survival in multiple myeloma.

OBJECTIVE: To evaluate serum lactate dehydrogenase (LDH) as a prognostic factor in previously untreated patients with multiple myeloma. DESIGN: Study of 391 consecutive patients with uniformly treated multiple myeloma, followed until death in 63% of patients. SETTING: Tertiary, referral cancer center. PATIENTS: A total of 391 consecutive, previously untreated, symptomatic patients with various stages of multiple myeloma. INTERVENTION: Various chemotherapy regimens that included doxorubicin or glucocorticoids, or both, with a consistent response rate (53%). MEASUREMENTS: Outcomes included clinical response based on a 75% reduction of calculated tumor load and survival time from treatment. Univariate and multivariate analyses were used. MAIN RESULTS: Eleven percent of patients showed a high serum LDH level of more than 5.0 mukat/L (300 U/L). An elevated LDH level was seen more frequently with a rise in the tumor load; an increased level was present in 26% of patients with high tumor mass. A high LDH level was associated with plasma cell leukemia or lymphoma-like clinical features (43%) and with plasma cell hypodiploidy (17%). Only 20% of patients with elevated LDH levels responded to chemotherapy compared with a response rate of 57% for patients with low levels of LDH. Using multivariate analysis, LDH was a significant independent predictor of response (P = 0.001), with an odds ratio of 0.25 (95% Cl, 0.11 to 0.57). A high LDH level was associated with a short median survival (9 months) and showed the highest relative risk (2.63; Cl, 1.75 to 3.95; P = 0.001). CONCLUSIONS: Elevation of the LDH level suggests the presence of occult extraosseous disease and high tumor mass. The LDH level is a predictor of a poor prognosis in selected patients who should be considered for early intensive treatment.

Antineoplastic Combined Chemotherapy Protocols↗

An effective acute graft-vs.-host disease prophylaxis with minidose methotrexate, cyclosporine, and single-dose methylprednisolone.

Cyclosporine and methotrexate at standard doses (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11, total 45 mg/m2) are effective in the prophylaxis of acute graft-vs.-host disease. However, the combination has significant early toxicities with delayed engraftment, increased mucositis, and hepatotoxicity. We modified the combination by adding single-dose methylprednisolone and lowered the total dose of methotrexate to 35 mg/m2 (5 mg/m2 on days 1, 3, and 6, and then 10 mg/m2 on days 11 and 18) and then to 20 mg/m2 (5 mg/m2 on days 1, 3, 6, and 11) in an attempt to decrease these side effects in two sequential consecutive groups of patients. We demonstrated that the modified regimens maintained the efficacy with reduced toxicities. The rate of engraftment was comparable to cyclosporine alone and the hepatotoxicity was reduced with reduced doses of methotrexate. Factors such as early immunosuppression of the host, intravenous immunoglobulin, the timing of steroid administration, nucleotide free diet and germ free environment may contribute to the effectiveness of the combination and permit reduction of methotrexate dose.

Bone Marrow Transplantation↗

Predictive factors for effective salvage therapy of nonseminomatous germ cell tumors of testis.

Twenty-four patients with metastatic and chemotherapy-refractory nonseminomatous germ cell tumors of the testis were treated with various chemotherapy regimens upon failure. Eight of the 24 patients (33%) are alive and disease-free after salvage therapy with a median follow-up of sixteen months. Prognostic factors tested included those known to be predictive for initial response to therapy (clinical stage and degree of elevation of the biomarkers). In addition, time to initiation of salvage therapy and response to initial chemotherapy were assessed as variables. Our data suggest that patients with solitary organ metastases following relapse, and response to initial chemotherapy are favorable predictors for response to salvage treatment. All the patients with solitary organ metastases (5/5 [100%]) but only 3/19 (16%) of the patients with multiple metastatic sites were salvaged. Patients with delayed initiation of salvage therapy had a reduced likelihood of achieving a complete remission but this was not statistically significant. The variables identified need to be incorporated into future trials testing the efficacy of salvage therapy for patients with nonseminomatous tumors of the testis.

Antineoplastic Combined Chemotherapy Protocols↗

Prophylaxis of cytomegalovirus infection with ganciclovir in allogeneic marrow transplantation.

Cytomegalovirus (CMV) infection is one of the most common causes of morbidity and mortality after allogeneic marrow transplantation. We studied 14 consecutive CMV-seropositive patients adding ganciclovir (2.5 mg/kg i.v. every 8 hours for 7 days prior to transplant and 6 mg/kg three times a week after neutrophils became greater than 0.5 x 10(9)/l and the patients were platelet transfusion-independent until d 70) to our previous prophylaxis regimen which consisted of intravenous immunoglobulin and acyclovir. The result was compared with 30 consecutive patients whom we studied with our previous regimen. The addition of ganciclovir did not cause any extra toxicities. The incidence of interstitial pneumonitis and cumulative probability of CMV excretion in the first 100 d post-transplantation was significantly reduced (p = 0.038 and p = 0.035 respectively). The result shows that addition of ganciclovir significantly decreased the incidence of CMV infection in the early post-transplantation period.

Adolescent↗

Intravesical interferon alfa-2b administration in the treatment of superficial bladder tumors.

This study was undertaken to assess the value of intravesical interferon alfa-2b treatment in preventing the recurrences of superficial transitional cell carcinoma of the bladder. A total of 30 patients aged from 33 to 78 entered the protocol. The intravesical instillations were performed once a week for 8 weeks. A solution of 10 x 10(6) IU interferon alfa-2b in 30 ml of normal saline was used. Follow-up ranged from 12 to 28 months. Of the 30 patients, 19 (63.33%) were tumor free at the end of follow-up. Of the remaining 11 patients, 7 presented with recurrent superficial tumors and 4 with invasive bladder tumors. No side effects were noted.

Administration, Intravesical↗

Meningoencephalitis and peripheral neuropathy complicating adult Still's disease.

We describe a patient with adult onset Still's disease (AOSD) who developed meningoencephalitis, sensorimotor peripheral neuropathy and uveitis during the course of disease. An abnormal cerebrospinal fluid and changes on nerve conduction studies substantiated the diagnoses of these unusual complications. The meningoencephalopathy improved before corticosteriod treatment, and the peripheral neuropathy and other features of AOSD have responded to corticosteroids. Our case illustrates the rare occurrence of both central and peripheral neurological involvement in AOSD.

Adult↗

Rhabdomyosarcoma of the testis.

A case of pure rhabdomyosarcoma of the testis is reported. The origin of these tumors is discussed and it is believed that they are teratomas with rhabdomyoblastic overgrowth of the cells. Prophylactic retroperitoneal lymph node dissection is recommended at the time of the orchiectomy, in those cases where there is no evidence of lymph node metastases.

Adolescent↗

Genetic markers in renal adenocarcinoma.

The distribution of phenotypes and gene frequencies of the 3rd component of complement (C3), group-specific component (Gc), haptoglobin (Hp) and transferrin (Tf) were studied in 50 patients with renal adenocarcinoma. The statistical analysis of our findings in comparison to the frequency of these genes in the general population does not reveal any correlation between the distribution of the Hp and Tf phenotypes and the disease. On the contrary, a statistically significant association was found between renal adenocarcinoma and C3F and Gc2 genes. The relative risk incidence of this malignancy is 2.07 and 1.94 respectively for the carriers of these genes. These data indicate that genetic factors, possibly related to the immune mechanisms and calcium metabolism, play a role in the pathogenesis of renal adenocarcinoma.

Adenocarcinoma↗