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Biomedical subjects

M A Dimopoulos

Publications and source records attributed to M A Dimopoulos.

At least 127 records · Page 7Linked to original sources

Testicular lymphoma: late relapses and poor outcome despite doxorubicin-based therapy.

PURPOSE: To determine the significance of the International Prognostic Index (IPI) score in adults with testicular lymphoma treated with doxorubicin-based regimens. PATIENTS AND METHODS: Untreated adults with testicular lymphoma who presented between 1969 and 1993 were studied. Those with Ann Arbor stages III and IV were included if they had a testicular mass at presentation. RESULTS: We identified 22 patients, 21 with intermediate-grade and one with high-grade lymphoma. All 10 patients with an IPI score < or = 1 had Ann Arbor stage I disease, whereas the 12 with an IPI score more than 1 had Ann Arbor stage II to IV disease. Complete remission (CR) was achieved in 73% of patients. At 153 months, 22% of all complete responders and 40% and 0% of those with IPI scores < or = 1 and more than 1, respectively, remained in CR (P = .01). With a median follow-up time of 113 months for survivors, the failure-free survival (FFS) rate at 153 months was 16% for all patients or 32% and 0% for those with IPI scores < or = 1 and more than 1, respectively (P = .02). The CNS or contralateral testis were involved in all patients who failed to respond to primary therapy and in 50% of those who relapsed from CR. CONCLUSION: The prognosis of patients with testicular lymphoma appears poor despite doxorubicin-based chemotherapy. On the basis of failures in the CNS and contralateral testis, we recommend prophylactic intrathecal chemotherapy and scrotal radiotherapy for all patients. Those with an IPI score < or = 1 can be treated with conventional doxorubicin-based regimens, but those with an IPI score more than 1 should be considered for investigational systemic therapy.

Adult↗

Waldenström macroglobulinemia presenting as a renal or perirenal mass: clinical and radiographic features.

Manifestations of macroglobulinemic lymphoma include lymphadenopathy, splenomegaly and bone marrow involvement. Renal presentations are unusual and complications of renal function are even less frequent. A review of all patients diagnosed with Waldenström macroglobulinemia at our institution from January 1987 to December 1993, revealed 4 cases (6%) with renal presentations. We describe these cases with their associated clinical and radiologic features.

Diagnosis, Differential↗

Rising serum lactate dehydrogenase often caused by granulocyte-or Granulocyte-macrophage colony stimulating factor and not tumor progression in patients with lymphoma or myeloma.

Since rising serum lactate dehydrogenase (LDH) heralds progression in patients with lymphoma or myeloma we investigated the significance of its elevations during chemotherapy supported by granulocyte (G-) or Granulocyte-Macrophage (GM-) colony stimulating factors (CSF). To Exclude effects of resistant disease we analyzed 52 courses of therapy in 36 responding patients. During hematologic recovery LDH increased above normal in 53% and 85% of patients with leukocyte counts of 10,000/microL and 15,000/microL, respectively. After CSF discontinuation LDH fell to or towards normal during 20 courses with adequate follow-up. Therefore rising serum LDH in patients with lymphoma or myeloma may be caused the CSF administration during chemotherapy and not by progressive disease. Proper identification of this effect can prevent unnecessary tests or treatment delays.

Adult↗

Pharmacokinetics, dosimetry and toxicity of holmium-166-DOTMP for bone marrow ablation in multiple myeloma.

UNLABELLED: In this Phase I clinical trial, six multiple myeloma patients who had not responded to conventional therapy and were scheduled for bone marrow transplantation received a bone-seeking radiopharmaceutical for bone marrow ablation. The pharmacokinetics, dosimetry, and toxicity of this radiopharmaceutical were studied. METHODS: Patients received from 519 mCi to 2.1 Ci (19.2 GBq to 77.7 GBq) of holmium-166 (166Ho) complexed with a bone-seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid). The reproducibility of pharmacokinetics from multiple injections of 166Ho-DOTMP administered to these myeloma patients was demonstrated from blood (r2 = 0.926) and whole-body retention (r2 = 0.983), which allowed therapeutic parameters to be determined from a diagnostic study. RESULTS: Over 50% of the 166Ho-DOTMP injected dose was excreted within 2-3 hr postinjection, increasing to 75%-85% over a 24-hr period. Rapid blood clearance minimized radiation dose to nontarget tissue: less than 10% of the injected activity was retained in the blood pool at 1 hr postinjection, and less than 2% remained after 5 hr. The total radiation absorbed dose delivered to the bone marrow for the six patients ranged from 7.9 Gy to 41.4 Gy. CONCLUSION: All patients demonstrated severe bone marrow toxicity with a white blood cell (WBC) count < 1,000 cells/microliters, two patients exhibited marrow ablation (WBC count < 100 cells/microliters), and no other toxicity > or = grade 2 was observed in any of the patients.

Bone Marrow↗

Early myeloablative therapy for multiple myeloma.

The value of early myeloablative therapy supported by autologous bone marrow or blood progenitor cells was assessed in 72 patients with multiple myeloma who were treated within 1 year of initial therapy. Forty-five patients were consolidated during remission, and 27 patients were treated for primary refractory disease. Outcomes were compared with those of similar patients who did not receive intensive treatment primarily for socioeconomic reasons. Among patients who had responded previously, myeloablative therapy increased the rate of complete remission from 5% to 45% (P < .01) but did not prolong progression-free intervals or survival times. The same treatment controlled the myeloma in 70% of patients with primary resistant disease and prolonged the median survival from 37 to 83 months (P = .03). Intensive treatment for primary resistant myeloma administered later in the disease course resulted in significantly lower response rates and shorter progression-free intervals. Current myeloablative regimens supported by autologous stem cells appeared useful primarily in patients with primary resistant disease during the first year of therapy.

Adult↗

Calcitriol production in hypercalcemic and normocalcemic patients with non-Hodgkin lymphoma.

OBJECTIVE: To determine the following: a reference range for serum calcitriol during hypercalcemia in a control group of patients with myeloma in whom calcitriol production is known to be appropriately suppressed; the incidence of elevated serum calcitriol levels in hypercalcemic patients with non-Hodgkin lymphoma according to this derived reference range; and the incidence of abnormal calcium metabolism in normocalcemic patients with non-Hodgkin lymphoma. DESIGN: Prospective clinical study. SETTING: Referral cancer center. PATIENTS: 2 groups of hypercalcemic patients: 16 control patients with myeloma and 22 patients with non-Hodgkin lymphoma divided into those with elevated or normal serum calcitriol levels; 1 group of 22 normocalcemic patients with non-Hodgkin lymphoma. MEASUREMENTS: Serum chemistries and intact parathyroid hormone, calcitriol, parathyroid hormone-related protein, and urinary electrolyte levels. RESULTS: On the basis of the mean serum calcitriol level of the control group plus 3 standard deviations, the reference range for serum calcitriol during hypercalcemia was defined as less than 42 pg/mL. Although serum calcium and parathyroid hormone levels in the study patients were similar to those in controls, 12 of the 22 hypercalcemic patients with non-Hodgkin lymphoma (55%) had serum calcitriol levels greater than 42 pg/mL (range, 51 to 170 pg/mL). No features distinguished the patients with elevated serum calcitriol levels from those with normal levels. Seventy-one percent of normocalcemic patients with non-Hodgkin lymphoma were hypercalciuric, and 18% had serum calcitriol levels greater than the normocalcemic reference range (20 to 76 pg/mL). CONCLUSIONS: Serum calcitriol levels are elevated in most hypercalcemic patients with non-Hodgkin lymphoma in the absence of elevated serum levels of parathyroid hormone, which implicates extrarenal calcitriol production in the pathogenesis of this syndrome. Abnormal calcium metabolism, hypercalciuria, and dysregulated calcitriol production are also common in normocalcemic patients with non-Hodgkin lymphoma.

Adult↗

Allogeneic bone marrow transplantation for leukemia following piperazinedione and fractionated total body irradiation.

Between 1980 and 1988, 126 patients with leukemia were treated with piperazinedione and fractionated total body irradiation (TBI) followed by allogeneic bone marrow transplantation from HLA matched siblings. Sixty-one patients had acute myelogenous leukemia, 46 acute lymphoblastic leukemia, and 19 chronic myelogenous leukemia. Patients with acute leukemia in first complete remission were transplanted only if perceived to have a low probability of remaining in remission with conventional therapy. The toxicity from the preparative regimen was similar to that of cyclophosphamide and TBI except that none of the patients in the study had hemorrhagic cystitis or veno-occlusive disease. After a median follow up of 114 months, 29 patients (23%) are still alive without relapse. The survival of patients with acute myelogenous or lymphoblastic leukemia transplanted in their first remission were 35% and 43%, respectively. The survival of patients transplanted in their first chronic phase of chronic myelogenous leukemia was 60%. The results of this preparative regimen are comparable to those of cyclophosphamide and TBI.

Adolescent↗

Regression of gastric lymphoma of mucosa-associated lymphoid tissue with antibiotic therapy for Helicobacter pylori.

Regression of low-grade B cell gastric lymphoma of mucosa-associated lymphoid tissue after eradication of Helicobacter pylori with antibiotic therapy was recently shown in a small number of patients with low-volume tumors. A patient with a > 10 cm nodular gastric mucosa-associated lymphoid tissue lymphoma that caused hematemesis and weight loss is described. Antibiotic therapy of H. pylori resulted in full clinical recovery and resolution of the mass lesion and morphological features of lymphoma on routine histological examination. However, monotypic immunostaining of plasma cells persisted in a separate and grossly normal-appearing region of the stomach. Antibiotic therapy may be of benefit in patients with mucosa-associated lymphoid tissue lymphoma with mass lesions and significant signs and symptoms, but periodic search for residual lymphoma is needed.

Female↗

Neoadjuvant cisplatin and interferon-alpha 2B in the treatment and organ preservation of penile carcinoma.

We investigated the antitumor activity and toxicity of cisplatin and interferon-alpha 2B as the primary treatment of penile carcinoma. A total of 13 consecutive patients with nonmetastatic, histologically confirmed invasive squamous cell carcinoma of the penis underwent treatment consisting of 20 mg./m.2 cisplatin intravenously and 5 x 10(6) mu./m.2 interferon-alpha 2B subcutaneously daily for 5 consecutive days. An equivalent dose of interferon was then administered subcutaneously every 2 days for 3 weeks and the regimen was repeated at 28-day intervals. Of 12 evaluable patients 9 responded: 4 achieved a pathologically confirmed complete remission of 38+, 21+, 10 and 7 months in duration (2 with relapse were treated with local therapy and remain with no evidence of disease), and 5 achieved a partial response, underwent surgical removal of residual disease and remained disease-free for 14+ to 24+ months. The most significant toxicities were anemia in 5 patients and reversible renal impairment in 3 but no patient had neutropenic fever or required platelet transfusion. We conclude that primary treatment with cisplatin and interferon-alpha 2B induced responses in 75% of 12 patients with penile carcinoma and allowed for a less radical operation than originally scheduled. A larger number of patients and longer followup will be required to confirm these encouraging preliminary results.

Adult↗

Pattern of failure and survival of patients with metastatic urothelial tumors relapsing after cis-platinum-based chemotherapy.

Cis-platinum-based chemotherapy combinations have improved the outcome of patients with metastatic urothelial tumors, since two-thirds of these patients respond to treatment. Nevertheless, the majority of such patients have relapse within a median of 12 months. To define the pattern of failure and subsequent outcome, we retrospectively assessed 58 consecutive patients with relapse after prior response to cis-platinum-based combination chemotherapy. Of the patients who presented initially with local-regional metastases, 74% had relapse with involvement of a similar site, while only 26% of these patients had visceral metastases at relapse. The median survival after relapse was 9 months, and parameters associated with longer survival were local-regional relapse (10.7 months) and response to salvage chemotherapy (12.6 months). These data suggest that select patients with urothelial tumors and local-regional metastases may benefit from consolidation therapy with surgery or radiotherapy after maximum response to chemotherapy.

Adult↗

2Chlorodeoxyadenosine therapy of patients with Waldenström macroglobulinemia previously treated with fludarabine.

BACKGROUND: Fludarabine monophosphate and 2Chlorodeoxyadenosine are nucleoside analogues with activity against Waldenström macroglobulinemia. However, it is not clear whether prior exposure to one analogue precludes response to the other compound. PATIENTS AND METHODS: Fourteen patients with Waldenström's macroglobulinemia and prior exposure to fludarabine were treated with two courses of 2chlorodeoxyadenosine. RESULTS: Three out of four patients that had previously responded to fludarabine and were relapsing from unmaintained remission, achieved a partial response with 2chlorodeoxyadenosine therapy. However, only one out of 10 patients with disease resistant to fludarabine responded to 2chlorodeoxyadenosine. CONCLUSIONS: 2chlorodeoxyadenosine may be effective in patients with Waldenström macroglobulinemia sensitive to fludarabine. However, this compound has limited activity for patients with disease resistant to fludarabine.

Aged↗

Primary therapy of multiple myeloma with paclitaxel (taxol).

BACKGROUND: The treatment of multiple myeloma remains unsatisfactory and new active agents are needed. Paclitaxel is effective against a variety of solid tumors and we assessed the utility against multiple myeloma. PATIENTS AND METHODS: From March 1993 to May 1994, we treated 33 patients with newly diagnosed multiple myeloma with paclitaxel given intravenously at a dose of 125 mg/m2 over 24 hours (13 patients) or at a dose of 135 mg/m2 over 3 hours (20 patients). RESULTS: Five of 33 patients responded (15%; 95% CI: 5 to 32%) with an unmaintained remission of 3-11+ months. Severe but reversible neutropenia was the major dose limiting toxicity, but myalgias and alopecia were also common. CONCLUSION: Paclitaxel was slightly active against multiple myeloma. Whether higher doses or new analogues of this agent can produce superior results requires further study.

Adult↗

Primary plasma cell leukaemia.

Among 750 previously untreated patients with multiple myeloma, 27 (4%) presented with plasma cell leukaemia. All but one patient had high tumour mass and, when compared with comparable patients without leukaemia, more frequent extraosseous involvement, thrombocytopenia, high serum lactate dehydrogenase and hypodiploid plasma cells. Most patients also had complex cytogenetic abnormalities. Treatment with standard melphalan-prednisone was ineffective, with a median survival of 2 months, but more intensive chemotherapy induced responses in approximately one-half of the patients, with a median survival of 20 months. Primary plasma cell leukaemia usually results from the proliferation and extramedullary expansion of immature plasma cells and requires prompt and intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Intensive chemotherapy with blood progenitor transplantation for primary resistant multiple myeloma.

This study assessed the feasibility and effect of blood progenitors as the only source of haemopoietic support for myeloablative therapy for patients with primary resistant multiple myeloma and markedly infiltrated bone marrow. 17 patients with advanced, primary resistant myeloma received a priming regimen of cyclophosphamide (3 g/m2) and etoposide (900 mg/m2) with GM-CSF. During haematological recovery, at least 2 x 10(6) CD34+ mononuclear cells/kg were collected from each patient with 4-12 leukaphereses. High-dose chemotherapy was then given which consisted of thiotepa (750 mg/m2), busulfan (10 mg/kg) and cyclophosphamide (120 mg/kg) followed by reinfusion of the blood progenitors. Haemopoietic reconstitution was rapid with recovery of granulocytes to > 1.0 x 10(9)/l after a median of 10 d and of platelets to 50 x 10(9)/l after a median of 29 d. The myeloma responded in 10/17 patients for a projected median duration of at least 12 months. Survival was prolonged significantly in comparison with the outcome of control patients who did not receive intensive treatment. Blood progenitors, assessed from the number of CD34+ cells, produced early haemopoietic recovery after myeloablative therapy that induced sustained control of advanced and resistant multiple myeloma.

Adult↗

Multiple myeloma: MR patterns of response to treatment.

PURPOSE: To assess changes in the magnetic resonance (MR) appearance of the spine in patients with multiple myeloma who responded to chemotherapy. MATERIALS AND METHODS: Twenty patients with multiple myeloma underwent MR imaging of the spine before and after chemotherapy. Sagittal T1-weighted images were obtained before and after administration of contrast material. MR patterns of marrow involvement before treatment were classified as focal, diffuse, or variegated. The changes seen on MR images after treatment were analyzed and correlated with the clinical response as defined with standard criteria. RESULTS: Patterns of complete response included resolution of marrow abnormality or persistent abnormality without enhancement or with peripheral rim enhancement. Conversion of a diffuse to a variegated or focal pattern and a decrease in the amount of marrow abnormality with persistent enhancement were observed in patients who showed a partial response. Ten patients sustained new or progressive compression fractures after successful therapy. CONCLUSION: Recognition of spinal MR patterns of response to treatment supported the occurrence of remission in patients with multiple myeloma. MR findings may help clarify response to therapy in patients with equivocal clinical changes or nonsecretory myeloma.

Adult↗

Primary therapy of Waldenström's macroglobulinemia with 2-chlorodeoxyadenosine.

PURPOSE: To assess the activity of 2-chlorodeoxyadenosine (2CdA) as primary therapy for patients with Waldenström's macroglobulinemia. PATIENTS AND METHODS: 2CdA was given to 26 consecutive, previously untreated and symptomatic patients with Waldenström's macroglobulinemia. 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 up without further therapy and were scheduled to receive two additional treatments with 2CdA on disease relapse. RESULTS: Twenty-two of 26 patients responded to the 2CdA therapy (85%; 95% confidence interval [CI], 65% to 96%), including three patients who achieved a complete response and 19 patients who had a partial response. Treatment was well tolerated, with no acute hematologic toxicity. A marked and sustained reduction of CD4+ lymphocytes occurred in all patients and may have contributed to a fatal infection with disseminated herpes simplex in one patient. With a median follow-up of 13 months, five patients have relapsed and all re-treated patients have responded again to 2CdA. CONCLUSION: 2CdA is highly active in previously untreated patients with Waldenström's macroglobulinemia. A limited program of treatment induced responses of good quality and long duration in more than 80% of patients.

Adult↗