Acute lobar nephronia as the presenting manifestation of hyperparathyroidism.
Explore the source record for details and available documents.
Acute Disease↗
Biomedical subjects
M A Dimopoulos
Publications and source records attributed to M A Dimopoulos.
Treatment of Langerhans cell histiocytosis with 2 chlorodeoxyadenosine.
Langerhans-cell histiocytosis (LCH) is a rare condition with a wide clinical spectrum and variable prognosis. Patients with multisystem LCH have been treated with a variety of agents but may develop resistant and progressive disease. Based on a preliminary encouraging report on the activity of 2 chlorodoxyadenosine in this disease, we administered this agent to a patient with LCH which was resistant to corticosteroids and etoposide. After 4 courses of treatment the patient achieved a complete remission which is currently ongoing for 12 months. 2 CdA appears to be effective in patients with resistant LCH and warrants investigation in previously untreated patients with poor risk disease.
Adult↗
Very late relapse of Hodgkin's disease after 24 years of complete remission.
With current treatment modalities, most patients with early stage Hodgkin's disease (HD) can be cured. Patients destined to relapse, usually do so within 3 years after treatment completion. Late relapses do occur but disease recurrence beyond 15 years is extremely rare. We report a patient with clinical stage IIA nodular sclerosis HD, originally treated with radiotherapy alone, who relapsed 24 years after the initial diagnosis. Our patient's case indicates the possible need for lifelong surveillance of patients with Hodgkin's disease.
Adult↗
Primary parotid lymphoma: the effect of International Prognostic Index on outcome.
Since the reported survival and failure-free survival (FFS) of adults with primary parotid non-Hodgkin's lymphoma (NHL) is variable, we reviewed our experience of untreated adults with primary parotid NHL. Patients were eligible if they presented to the University of Texas M. D. Anderson Cancer Center Cancer between 1980 and 1995 with parotid enlargement and if the diagnosis of lymphoma was verified according the Working Formulation. Medical records were reviewed to determine Ann Arbor Stage (AAS), the International Prognostic Index (IPI) score, response to therapy, relapse, FFS, and survival. We identified 39 untreated adults with primary parotid NHL representing 1% of all lymphomas and 8.6% of all untreated parotid neoplasms. Three patients were excluded because of suboptimal therapy, leaving 36 patients eligible for outcome analysis. Of the 18 patients with low-grade NHL, two were treated with radiotherapy, eight with chemotherapy and radiotherapy, seven with chemotherapy only, and one with antibiotics. The complete remission (CR) rate was 94%, and with a median follow-up of 36 months for surviving patients the survival and failure-free survival (FFS) at 5 years were 94% and 78%, respectively. The 5-year FFS were not statistically different between patients with early (I or II) or advanced (III or IV) AAS (83% and 74%, respectively; p > 0.05) and favorable (0 or 1) or unfavorable (> 1) IPI scores (73% and 100%, respectively; p > 0.05). All 18 patients with intermediate-grade NHL were treated with doxorubicin-based chemotherapy which was followed by radiotherapy in six. The CR rate was 89%, and with a median follow-up of 51 months for surviving patients the survival and FFS at 10 years were 80% and 72%, respectively. In this group 10-year FFS was better in early than in advanced AAS (100% vs 0%, respectively; p = 0.01) and in favorable (0 or 1) than in unfavorable (> 1) IPI scores (86% vs 20%, respectively; p < 0.01). We conclude the the FFS of patients with low-grade NHL is 78% and not affected by AAS or IPI score. The FFS of patients with intermediate-grade NHL appears comparable with that of NHLs of other primary sites, being 86% for those with IPI < or = 1 and 20% for those with IPI 1. Patients with IPI > 1 should be entered on investigational protocols aiming to increase FFS.
Adult↗
Long-range amplification of genomic DNA detects the t(2;5)(p23;q35) in anaplastic large-cell lymphoma, but not in other non-Hodgkin's lymphomas, Hodgkin's disease, or lymphomatoid papulosis.
DESIGN: Determine the frequency of t(2;5)(p23;q35) in anaplastic large-cell lymphoma (ALCL), non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and lymphomatoid papulosis (LP). PATIENTS AND METHODS: The t(2;5) was detected with a long-range nested polymerase chain reaction (PCR) using 0.5 microgram of DNA (60,000-80,000 cells), 5'-primers from the NPM gene, 3'-primers from the ALK gene, agarose electrophoresis, hybridization, and autoradiography. Patients were evaluable if a 3016 base pair amplicon could be generated from tumor DNA with beta-globin primers. RESULTS: Amplicons were detected by PCR of genomic DNA from three ALCL cell lines and four primary ALCLs known to t(2;5) positive. DNA from t(2;5)-positive cell lines diluted 10(4)-fold or 10(5)-fold generated amplicons in 100% or 20% of reactions, respectively. Archival tumor DNA from 144 patients was amplifiable by beta-globin amplicons in 126 (88%) who are considered evaluable for this study. Twenty-two had ALCL, 69 other NHLs, 30 HD, and five LP. Genomic DNA PCR detected the t(2;5) in 5 of 22 with ALCL (23%, 95% confidence intervals [95% CI] 8%-45%) but not in those with NHLs, HD, or LP. Among ALCLs the t(2;5) was confined to 5 of 20 with nodal presentations (25%, 95% CI 9%-49%), among whom it was seen in 5 of 15 with T-cell or null-cell phenotype (33%, 95% CI 12%-62%), in 4 of 11 with age < 40 years (36%, 95% CI 11%-69%), and in 4 of 9 with nodal presentations, T-cell or null-cell phenotype, and age < 40 years (44%, 95% CI 14%-79%). Amplicon sizes were different between cell lines and patients, reflecting unique genomic DNA breakpoints, as confirmed by DNA sequencing, and served as an internal control against specimen cross-contamination in the laboratory. CONCLUSIONS: Long-range PCR of genomic DNA detects t(2;5) only in ALCL, but not in other NHLs, HD, or LP. Long-range PCR may be useful in establishing diagnosis, determining prognosis, and monitoring minimal residual disease in ALCL.
Adolescent↗
Cisplatin, ifosfamide, methotrexate and vinblastine combination chemotherapy for metastatic urothelial cancer.
PURPOSE: We investigated the activity of combination chemotherapy consisting of cisplatin, ifosfamide, methotrexate and vinblastine in patients with metastatic urothelial cancer. MATERIALS AND METHODS: A total of 32 consecutive patients was treated with 30 mg./m.2 cisplatin on days 1 through 3, 1.5 gm./m.2 ifosfamide with mesna on days 1 through 3, 30 mg./m.2 methotrexate and 3 mg./m.2 vinblastine on day 1 plus 5 micrograms./kg. granulocyte colonystimulating factor on days 7 through 11. Courses were repeated every 21 days for a maximum of 6 cycles. RESULTS: Major toxicity was granulocytopenia in 56% of patients, including 11 episodes of granulocytopenic fever. Anemia and thrombocytopenia developed in a third of the cases. No other significant toxicity or treatment related death was noted. An objective response was achieved in 20 patients (62.5%, 95% confidence interval 44 to 79). Median time to progression was 7 months and median survival was 13 months. CONCLUSIONS: The cisplatin, ifosfamide, methotrexate and vinblastine regimen appeared active in patients with metastatic urothelial carcinoma. This regimen was associated with significant but manageable hematological toxicity and the incidence of mucositis or renal impairment was low. Prospective randomized studies are needed to assess whether the addition of ifosfamide to other active agents will improve the survival of patients with this disease.
Adenocarcinoma↗
Second-line treatment of advanced non-small cell lung cancer with paclitaxel and gemcitabine: a preliminary report on an active regimen.
A phase II study of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/gemcitabine was conducted in patients with non-small cell lung cancer (NSCLC) who had failed first-line docetaxel- or cisplatin-based chemotherapy. Eligibility criteria included histologically confirmed measurable stage IIIB or IV NSCLC and previous exposure to docetaxel- or cisplatin-based regimens, World Health Organization performance status between 0 and 2, adequate hematologic parameters, and adequate hepatic, renal, and cardiac function. Gemcitabine (900 mg/m2) was given on days 1 and 8 as a 30-minute infusion; paclitaxel (175 mg/m2) was administered on day 8 as a 3-hour infusion after appropriate premedication. Granulocyte colony-stimulating factor (150 microg/m2 subcutaneously) was given on days 9 to 15. Treatment was repeated every 3 weeks until patients experienced disease progression. From October 1995 to December 1996, 26 patients with advanced NSCLC were enrolled (three stage IIIB, 23 stage IV). All 26 patients were assessable for toxicity, and 24 were evaluable for response. Two complete (8%) and five partial (21%) responses were observed, for an overall response rate of 29% (95% confidence interval, 11% to 47%). The median duration of response was 2.5 months and the median survival was 8 months. A median of three courses per patient was administered, and the median interval between courses was 21 days. The median delivered dose was 579 mg/m2/wk gemcitabine and 54.5 mg/m2/wk paclitaxel, corresponding to a relative dose intensity of 0.97 and 0.96, respectively. Grade 3/4 neutropenia occurred in two patients (8%). Grade 3 conjunctivitis occurred in one (4%) patient and grade 2/3 neurotoxicity in eight (31%) patients. Grade 3/4 and grade 2 fatigue occurred in four (15%) and eight (31%) patients, respectively. Other toxicities were mild to moderate. These preliminary results suggest that the paclitaxel/gemcitabine combination is an active and well-tolerated salvage regimen in patients with NSCLC previously treated with docetaxel- or cisplatin-based chemotherapy. The paclitaxel/gemcitabine combination merits further evaluation as first-line treatment.
Adult↗
Docetaxel (Taxotere) and gemcitabine in the treatment of non-small cell lung cancer: preliminary results.
A phase II study was performed to investigate the tolerance and efficacy of the combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and gemcitabine in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). To date, 24 patients (five with stage IIIB and 19 with stage IV NSCLC) have been treated according to the protocol: gemcitabine 900 mg/m2 was administered on days 1 and 8 as a 30-minute infusion and docetaxel 100 mg/m2 was administered on day 8 as a 1-hour infusion after appropriate premedication. Granulocyte colony-stimulating factor 150 microg/m2 subcutaneously was given on days 9 to 15. Treatment was repeated every 3 weeks. Grade 3/4 granulocytopenia occurred in seven (29%) patients, and one (4%) of these patients developed febrile neutropenia. Grade 3/4 thrombocytopenia and anemia were observed in three (13%) and one (4%) patient, respectively. Grade 2 neurotoxicity and fatigue occurred in one (4%) patient each. Other toxicities were mild. There were no treatment-related deaths. Eight patients experienced a partial response (53.3%; 95% confidence interval, 28.1% to 78.6%), and stable and progressive disease were documented in two (13%) and five (33%) patients, respectively. The median delivered dose was 600 mg/m2/wk and 33 mg/m2/wk for gemcitabine and docetaxel, respectively. These preliminary data suggest that the docetaxel/gemcitabine combination has significant antitumor activity and is well tolerated in chemotherapy-naive patients with NSCLC. The study is ongoing.
Adult↗
Amplification of genomic DNA demonstrates the presence of the t(2;5) (p23;q35) in anaplastic large cell lymphoma, but not in other non-Hodgkin's lymphomas, Hodgkin's disease, or lymphomatoid papulosis.
Anaplastic large cell lymphoma (ALCL) is a distinct clinicopathologic variant of intermediate grade non-Hodgkin's lymphomas (NHL) composed of large pleomorphic cells that usually express the CD30 antigen and interleukin (IL)-2 receptors, and is characterized by frequent cutaneous and extranodal involvement. With variable frequency ALCL bear the t(2;5)(p23;q35) chromosomal translocation that fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a novel protein kinase gene, Anaplastic Lymphoma Kinase (ALK), on chromosome 2p23. We determined the frequency of this translocation with a novel DNA polymerase chain reaction (PCR) technique using 0.5 microgram of genomic DNA, 5'-primers derived from the NPM gene and 3'-primers derived from the ALK gene and hybridization with internal probes. The presence of amplifiable DNA in the samples was tested with the inclusion in the PCR reaction of oligonucleotide primers designed to amplify a 3016-bp fragment from the beta-globin locus. NMP-ALK fusion amplicons were detected using DNA isolated either from all three ALCL cell lines tested, or from all four primary ALCL tumors known to contain the t(2;5)(p23;q35) translocation. Nested amplicons were detected by hybridization in 100% of specimens diluted 10(4)-fold and in 20% of those diluted 10(5)-fold. We subsequently examined archival genomic DNA from 20 patients with ALCL, 39 with diffuse large cell, 2 with mantle cell, 20 with peripheral T cell, 13 with low-grade NHL, 31 with Hodgkin's disease (HD), and 6 with lymphomatoid papulosis. Fusion of the NPM and ALK genes was detected in three of 18 patients with ALCL who had amplifiable DNA (17%, 95% confidence intervals 4% to 41%), but not in any patients with other NHL, HD, or lymphomatoid papulosis. The amplicon sizes were different in all cell lines and patients reflecting unique genomic DNA breakpoints. We conclude that with genomic DNA-PCR the rearrangement of the NPM and ALK loci is restricted to patients with ALCL. Further studies are needed to determine the prognostic significance of the NPM-ALK rearrangement, to determine whether its detection can aid in the differential diagnosis between ALCL. Hodgkin's disease, and lymphomatoid papulosis, and to establish the usefulness of the genomic DNA PCR in the monitoring of minimal residual disease in those patients whose tumors bear the t(2;5).
Adolescent↗
Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group.
BACKGROUND: Skeletal complications are a major clinical manifestation of multiple myeloma. These complications are caused by soluble factors that stimulate osteoclasts to resorb bone. Bisphosphonates such as pamidronate inhibit osteoclastic activity and reduce bone resorption. METHODS: Patients with stage III multiple myeloma and at least one lytic lesion received either placebo or pamidronate (90 mg) as a four-hour intravenous infusion given every four weeks for nine cycles in addition to antimyeloma therapy. The patients were stratified according to whether they were receiving first-line (stratum 1) or second-line (stratum 2) antimyeloma chemotherapy at entry into the study. Skeletal events (pathologic fracture, irradiation of or surgery on bone, and spinal cord compression), hypercalcemia (symptoms or a serum calcium concentration > or = 12 mg per deciliter [3.0 mmol per liter]), bone pain, analgesic-drug use, performance status, and quality of life were assessed monthly. RESULTS: Among 392 treated patients, the efficacy of treatment could be evaluated in 196 who received pamidronate and 181 who received placebo. The proportion of patients who had any skeletal events was significantly lower in the pamidronate group (24 percent) than in the placebo group (41 percent, P < 0.001), and the reduction was evident in both stratum 1 (P = 0.04) and stratum 2 (P = 0.004). The patients who received pamidronate had significant decreases in bone pain and no deterioration in performance status and quality of life. Pamidronate was tolerated well. CONCLUSIONS: Monthly infusions of pamidronate provide significant protection against skeletal complications and improve the quality of life of patients with stage III multiple myeloma.
Aged↗
Pseudohyperphosphatemia in multiple myeloma.
Explore the source record for details and available documents.
Aged↗
HyperCVAD for VAD-resistant multiple myeloma.
More effective and safer regimens are needed for patients who have advanced multiple myeloma resistant to or relapsing despite prior treatment with alkylating agents and VAD. We treated 58 such patients using the combination of twice daily cyclophosphamide (total dose 1.8 g/m2) and VAD (hyperCVAD). Treatment was given to outpatients followed by G-CSF at 5 microgram/kg/d until granulocyte recovery. Twenty-three patients responded (40%), with a median duration of granulocyte depression to less than 500/microliter of 4 days and a mortality rate of 2%. The median survival time for all patients was 15 months, and the median remission time of responding patients was 8 months. Patients who had low LDH, low B2M, or primary resistant disease lived significantly longer than patients without these features. The combination of fractionated cyclophosphamide and VAD provided an effective and safe rescue treatment for many patients who had advanced myeloma resistant to standard therapies.
Adult↗
Primary renal lymphoma: a clinical and radiological study.
PURPOSE: We assessed the incidence, clinical and radiological features, and prognosis of patients with renal lymphoma. MATERIALS AND METHODS: We studied 210 patients with symptoms, signs and and radiological findings suggestive of renal cell carcinoma. RESULTS: Final diagnosis in 6 of 210 patients (3%) was primary renal lymphoma. Radiological features were similar to those of renal cell carcinoma. Five of the 6 patients had an International Prognostic Index score of greater than 1. Despite appropriate chemotherapy, only 2 patients remain with complete remission. CONCLUSIONS: Primary renal lymphoma is unusual but not rare. The relatively poor prognosis in our patients could be attributed to the adverse prognostic factors associated with aggressive nodal lymphomas.
Aged↗
Myeloablative therapy for primary resistant multiple myeloma.
Myeloablative therapy supported by autologous bone marrow or blood stem cell transplantation was assessed in 41 patients who had multiple myeloma resistant to vincristine-doxorubicin by continuous infusion with high-dose dexamethasone (VAD) or other high-dose dexamethasone regimens. In patients who had high or intermediate tumor mass, the myeloma cell mass was reduced by more than 75% in 56% of patients and the survival time quadrupled in comparison with that of a matched control group. Later treatment resulted in a lower response rate and shorter remission. Current myeloablative regimens supported by autologous stem cells provided a useful treatment for patients who had advanced primary resistant multiple myeloma. Such treatment should be given early in the disease course to provide the best chance for remission, collecting blood stem cells with facility, and preventing complications that would increase the risk of the procedure.
Adult↗
Complications and supportive therapy of multiple myeloma.
The clinical spectrum of MM is variable. Infiltration of bone and bone marrow by malignant plasma cells results in severe osteopenia, lytic lesions, pathological fractures and anaemia. Occasionally, significant numbers of plasma cells circulate in the bloodstream. Hypercalcaemia and Bence Jones proteinuria are the main reasons for renal impairment, but amyloidosis and monoclonal immunoglobulin deposition should also be considered. Neurological impairment is most often due to spinal cord pressure by an extradural plasma cell tumour. In some patients, symptoms and signs of peripheral neuropathy may be present. Amyloidosis complicates the course of a minority of patients with MM and further impairs the performance of affected patients. Circulating monoclonal protein may increase serum viscosity, impair the function of platelets and coagulation factors, and behave as a cryoglobulin. The levels of uninvolved immunoglobulins are usually decreased, rendering patients susceptible to various bacterial infections. One or more of these complications provides a clue for the diagnosis, forms the basis for defining prognosis and must be managed expeditiously and concurrently, with the institution of specific treatment for the myeloma.
Amyloidosis↗
Treatment of Waldenstrom's macroglobulinemia resistant to standard therapy with 2-chlorodeoxyadenosine: identification of prognostic factors.
BACKGROUND: Few effective treatments are available for patients with Waldenstrom's macroglobulinemia that is resistant to standard therapies. We assessed the activity of 2-chlorodeoxyadenosine (2CdA) in patients with resistant macroglobulinemia in order to identify those most likely to benefit. PATIENTS AND METHODS: 2-chlorodeoxyadenosine was given to 46 consecutive patients with Waldenstrom's macroglobulinemia resistant to a combination of an alkylating agent and a glucocorticoid. Two courses were administered to outpatients at a dose of 0.1 mg/kg body weight per day for a 7-day continuous infusion using a portable pump through a central venous catheter. Responding patients were followed without further therapy. RESULTS: Twenty of 46 patients responded to 2CdA therapy (43%; 95 CI; 29 to 60%) with a significantly higher frequency of benefit among patients with disease relapsing off therapy (78%) or with primary resistant disease within the first year (57%) than in those with later phases of disease (22%). The median survival after treatment was 28 months and the median progression-free survival of responding patients was 12 months. The longest survival was measured in patients with primary refractory disease (projected median 36 months) and the shortest in those with disease in refractory relapse (median 13 months). CONCLUSION: 2-Chlorodeoxyadenosine is active against macroglobulinemic lymphoma resistant to standard regimens and most effective in patients with disease relapsing off treatment or during the first year of primary refractory disease. Little benefit was observed among patients with later phases of resistant disease who should receive alternative treatments.
Adult↗
The value of prostatic specific antigen in the early diagnosis of prostatic cancer: a Greek view.
OBJECTIVE: To assess whether it is worthwhile to screen asymptomatic men for prostate cancer using serum prostate specific antigen (PSA) and to determine how many patients could be cured of prostatic carcinoma if detected by screening. PATIENTS AND METHODS: Between June 1992 and January 1994 the serum PSA level of 1400 asymptomatic men over 50-years-old was assessed. Those men with PSA levels < 4 ng/mL were not evaluated further. Those men with PSA levels of 4-10 ng/mL underwent digital rectal examination (DRE) and transrectal ultrasonography (TRUS) and biopsies were taken when there were significant findings on DRE and/or TRUS. If the PSA levels were > 10 ng/mL patients were submitted for DRE and TRUS and, even if both examinations were negative, random biopsies were taken. Where cancer was detected the tumour was staged and if it was a clinically confined tumour a radical retropubic prostatectomy was performed. The pathological and clinical stages of the disease were then compared. RESULTS: The majority of patients (95%) had PSA levels of < 4 ng/mL. Forty-nine men had PSA levels of 4-10 ng/mL and of these 28 were biopsied, which detected 12 (24.5%) carcinomas. There were 20 men with PSA levels > 10 ng/mL and among them 11 (55%) were found to have carcinomas. Combining these figures, among the 1400 men there were 69 cases with PSA levels > 4 ng/mL and, using DRE and TRUS, 23 patients (33%) were diagnosed as having prostatic adenocarcinomas. Among these, one had metastatic disease, three had lymph node micrometastases during surgical exploration and 19 underwent radical prostatectomies. The pathological and clinical stages agreed in only eight patients. CONCLUSION: Only eight patients can be considered as cured because of the screening protocol and even this result is overoptimistic, as the future biological behaviour of these tumours is unknown. Therefore we cannot recommend screening for prostatic carcinoma among asymptomatic men in Greece.
Aged↗
Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma.
PURPOSE: To assess the prognostic significance of magnetic resonance (MR) imaging in patients with newly diagnosed asymptomatic multiple myeloma. PATIENTS AND METHODS: Thirty-eight consecutive patients with asymptomatic myeloma of low tumor mass and negative skeletal surveys underwent MR imaging of the thoracic and lumbosacral spine. The presence and patterns of marrow involvement were correlated with standard laboratory parameters and time to disease progression. RESULTS: Nineteen patients (50%) had evidence of marrow involvement at spinal MR imaging. MR patterns of marrow involvement were classified as diffuse (five patients), variegated (nine), and focal (five). Patients with abnormal MR imaging studies required therapy after a median of 16 months, versus 43 months for those with normal MR studies (P < .01). CONCLUSION: Abnormal marrow patterns were present in half of patients with asymptomatic myeloma. An abnormal MR study of the spine identified asymptomatic patients who were likely to require treatment earlier than those with a normal MR study. A normal MR pattern provided additional justification to defer institution of chemotherapy. However, MR imaging remains an investigational tool to stage patients with multiple myeloma until more data are accumulated.
Adult↗