Search PubMed⌕ Search

Biomedical subjects

D J Straus

Publications and source records attributed to D J Straus.

At least 37 records · Page 2Linked to original sources
PubMed1993

Modern treatment approaches for Hodgkin's disease.

Recent studies are refining the treatment approaches of radiation therapy and combination chemotherapy in Hodgkin's disease. In early-stage disease, attempts are being made to lessen the toxicity of treatment while maintaining excellent results. Optimal results are achieved in advanced disease with combined radiation therapy and chemotherapy, most often with alternating or hybrid regimens. Several groups have attempted to define a poor-prognosis group of patients with advanced disease who might be candidates for more intensive treatment.

Combined Modality Therapy↗
PubMed1993

Phase I dose-escalation trial of iodine 131-labeled monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma.

PURPOSE: Eighteen patients with recurrent or refractory CD21-positive, non-Hodgkin's lymphoma (NHL) were treated in a phase IA dose-escalation therapeutic trial of iodine 131 labeled to a fixed dose of OKB7. METHODS: Individual doses of 30 to 50 mCi of 131I on 25 mg OKB7 were administered 2 to 3 days apart to achieve four total 131I-OKB7 dose levels of 90, 120, 160, and 200 mCi. Pharmacology, dosimetry, therapeutic effects, toxicity, human anti-mouse antibody (HAMA) response, and maximum-tolerated dose (MTD) were determined. Patients were evaluated by imaging studies (including whole-body gamma camera or single-photon emission computed tomography [SPECT] scans), flow cytometric analysis, bone marrow biopsy, and serial blood sampling. RESULTS: Median plasma and whole-body half-lives (T1/2) were 16 hours and 14 hours, respectively. Plasma and whole-body radiation doses were 0.0081 Gy/mCi and 0.0022 Gy/mCi, respectively. Specific tumor visualization was noted in eight of 18 patients. HAMA was detected in 12 of 16 patients. Nonhematologic toxicity was limited to asymptomatic elevations of thyroid-stimulating hormone (TSH) in five of 15 patients. Hematologic toxicity was observed in six of 18 patients, but was severe in only two patients. MTD in patients with diffuse lymphomatous bone marrow involvement was determined to be 200 mCi in four divided doses of 50 mCi 131I/25 mg OKB7. Antitumor activity was observed in 13 of 18 patients (one partial response [PR] and 12 mixed responses) and was dependent on the 131I-OKB7 dose administered. In general, palpable peripheral lymphadenopathy, enlarged spleens, skin lesions, and circulating OKB7-positive peripheral lymphocytes responded most readily to treatment. 131I-OKB7 was safely administered to a patient in leukemic phase of NHL with prompt subsequent loss of approximately 1 kg of tumor cells from the peripheral blood without associated tumor lysis syndrome. CONCLUSION: Because antitumor activity with tolerable toxicity was observed in the majority of this group of heavily pretreated patients, phase II investigation of mAb OKB7 radioconjugates in the therapy of NHL is warranted.

Adult↗
PubMed1993

Accelerated hyperfractionated total-lymphoid irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for refractory and relapsing patients with Hodgkin's disease.

PURPOSE: To evaluate the feasibility and therapeutic effect of accelerated hyperfractionated total-lymphoid irradiation (TLI), high-dose chemotherapy, and autologous bone marrow transplantation (AuBMT) in patients with relapsing or chemotherapy-resistant Hodgkin's disease (HD). PATIENTS AND METHODS: Forty-seven patients with HD who either relapsed after chemotherapy (n = 19), or failed to respond (n = 28) to at least two regimens of combination chemotherapy were studied. No patient received prior radiation therapy (RT). Treatment started with reinduction with standard-dose chemotherapy, followed by involved-field irradiation (15 Gy) to areas of relapsed or persistent disease and TLI (20.04 Gy given in 1.67 Gy fractions three times per day for 4 days). Subsequently, patients received etoposide and high-dose cyclophosphamide, followed by infusion of unpurged autologous bone marrow. All surviving patients had a minimum follow-up duration of 1 year. The median follow-up duration for survivors was 40+ months, and the maximum follow-up duration was 80+ months. RESULTS: Of the 47 patients treated, eight (17%) died of toxicity during the peritransplant period. Twenty-nine of the remaining 39 assessable patients (74%) attained a complete response (CR), while 10 remained with residual disease and progressed early after AuBMT. Four of the CR patients (14%) relapsed and 25 patients remained alive and free of disease. The actuarial disease-free survival (DFS) rate for the entire group at 6.5 years was 50%. Patients who received the protocol for relapsing HD had a significantly better DFS rate (79%) compared with patients treated for continuous refractory disease (DFS, 33%; P < .03). CONCLUSION: Previously unirradiated patients with relapsing or chemotherapy-resistant HD who have exhausted conventional chemotherapy may still respond to an aggressive therapeutic approach consisting of accelerated hyperfractionated TLI, high-dose chemotherapy, and AuBMT rescue. This program offers a potential for long-term DFS to approximately one half of patients who would otherwise have a dismal prognosis with standard-dose salvage therapy.

Adolescent↗
PubMed1992

Four cycles of chemotherapy and regional radiation therapy for clinical early-stage and intermediate-stage Hodgkin's disease.

To achieve a high percentage of durable complete remissions (CR) and prolonged survivals and reduce toxicity in patients with early-stage and intermediate-stage Hodgkin's disease, a randomized trial of four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) versus four cycles of thiotepa, bleomycin, and vinblastine (TBV) combined with regional radiation therapy (RT) was conducted. For MOPP and RT, the CR percentage was 98% (60 of 61), and at 5 years, the percentage of patients in CR was 90%, with freedom from progression of 89% and overall survival of 91%. For TBV and RT, the CR percentage was 93% (55 of 59), with a 5-year duration of CR of 83%, freedom from progression of 81%, and overall survival of 91% (P greater than 0.15). The median follow-up was 65 months (range, 7 to 96 months). For 27 patients with clinical Stage IIIA, the CR percentage for MOPP and RT was 75% (12 of 16), with 1 relapse and 4 deaths. For TBV and RT, the CR percentage for clinical Stage IIIA was 73% (8 of 11) with 2 relapses and 2 deaths. Short-term toxicity except for transient leukopenia was less for TBV and RT than for MOPP and RT. Good results are achievable with combined treatment without excessive toxicity.

Adolescent↗
PubMed1992

Comparison of technetium-99m-MIBI and thallium-201-chloride uptake in primary thyroid lymphoma.

A case of primary thyroid lymphoma demonstrating uptake of 99mTc-hexakis-2-methoxy isobutyl isonitrile (MIBI) is presented. The 99mTc-MIBI image more clearly delineated the extent of tumor as demonstrated on CT compared to 201Tl-chloride and [99mTc]pertechnetate images. Following two courses of chemotherapy, repeat radionuclide studies and CT scan showed complete resolution of the thyroid tumor. Technetium-99m-MIBI may be useful in the assessment of disease activity and monitoring response to treatment in patients with lymphoma.

Female↗
PubMed1991

Mitoxantrone, etoposide, mitoguazone and vinblastine chemotherapy (MV2) in relapsed and refractory lymphomas.

As part of a program to develop less leukemogenic chemotherapy regimens for the treatment of favorable prognosis Hodgkin's disease, a phase I-II trial of mitoxantrone, etoposide, mitoguazone, and vinblastine was used to treat patients with relapsed and refractory malignant lymphoma and Hodgkin's disease. An overall partial response rate of 41% was observed. Although useful responses were seen, the absence of complete remissions is disappointing.

Adolescent↗
PubMed1991

Impact of adjuvant radiation on the patterns and rate of relapse in advanced-stage Hodgkin's disease treated with alternating chemotherapy combinations.

The role of adjuvant radiation therapy (RT) in the management of advanced-stage Hodgkin's disease (HD) was analyzed in 222 patients who attained a complete remission (CR) with alternating chemotherapy combinations. Mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) or MOPP/ABV alternating with the lomustine, melphalan, and vindesine combination (MOPP/ABV/CAD) were similarly effective in inducing a CR in 222 of 270 (83%) patients. These patients were scheduled to receive consolidative RT to bulky disease or other critical sites of initial nodal involvement to a total dose of 2,000 cGy, with an optional additional boost of 1,000 cGy. However, only 125 (56%) patients received radiation to all initial nodal sites of disease. In 69 (31%) patients, only selected nodal sites were included in the radiation fields, and 28 (13%) did not receive any RT. Of the 222 CR patients, 42 (19%) relapsed during a median follow-up period of 6.5 years (range, 2 to 15 years). Of these, 26 (62%) patients relapsed exclusively in unirradiated nodal sites, six (14%) within irradiated sites, and 10 (24%) both within and outside irradiated fields. The actuarial 10-year relapse-free survival (RFS) and overall survival (OS) for patients receiving radiation to all initially involved nodal sites were 89% and 94%, respectively, compared with 68% and 71% (P less than .0001) for patients who had only partial or no RT. Cox proportional hazards regression analysis showed that RT to all sites of initial disease was the most significant independent covariate (P less than .005) affecting RFS and OS. These data demonstrate that residual microscopic disease is relatively frequent in patients with apparent CR after alternating combination chemotherapy, and that irradiation of all sites of initial nodal involvement decreases relapse and improves survival in advanced-stage HD.

Actuarial Analysis↗
PubMed1991

Diffuse large cell lymphoma. Prognostic factors with treatment.

Five successive chemotherapy protocols for stages II, III and IV diffuse large cell lymphoma (DLCL) have resulted in identical overall survivals. Between 35% to 45% of patients survived. In a multivariate analysis employing the Weibull model 3 factors were associated with shortened survival: bulky mediastinal and/or retroperitoneal disease, elevated serum LDH and advanced age. In young patients with bulky mediastinal and/or retroperitoneal disease and high serum LDH, autologous bone marrow transplantation following high dose chemotherapy and radiation therapy (RT) as part of the initial treatment have produced more promising results. In a randomized trial, a significantly longer disease-free survival was found for patients with stages I or IE diffuse lymphomas with RT followed by adjuvant chemotherapy than with RT alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Small non-cleaved-cell lymphoma (undifferentiated lymphoma, Burkitt's type) in American adults: results with treatment designed for acute lymphoblastic leukemia.

PURPOSE: Small non-cleaved-cell lymphoma (SNCL) "Burkitt's type," a rapidly growing lymphoma, has been rare among adults in the United States, but has greatly increased in incidence with the acquired immunodeficiency syndrome epidemic. This report details the results of treatment of adult SNCL with a series of protocols originally designed for the treatment of acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Between July 1973 and May 1987, 29 adults with newly diagnosed SNCL were treated at Memorial Hospital with intensive chemotherapy originally designed for ALL: the cyclophosphamide L-2, L-10, L-17, and L-20 protocols. Nine patients had positive serologies for human immunodeficiency virus (HIV) infection. One patient with all measurable disease resected was not evaluable for response. RESULTS: Sixteen of 28 evaluable patients (57%) achieved a complete remission with treatment. With follow-up as long as 153 months (median, 47 months), 50% of all patients and 59% of patients with negative or unknown HIV serologies have survived and are probably cured. Patients with an initial serum lactic acid dehydrogenase (LDH) level of greater than 500 U/L had a significantly shortened survival as compared with those with a lower serum LDH. Other pretreatment patient characteristics associated with a shortened survival of borderline statistical significance were high National Cancer Institute stage (C, D) and bone marrow involvement. These results are similar to those for ALL and lymphoblastic lymphoma and are comparable to those for American SNCL in the literature. CONCLUSIONS: Approximately one half of adults with SNCL are curable with intensive chemotherapy. More intensive chemotherapy with hematopoietic growth factor and/or autologous bone marrow or peripheral stem cell support may increase curability.

Adolescent↗
PubMed1990

Lymphoma and other HIV-associated malignancies.

The immunodeficient state that evolves in persons infected with the human immunodeficiency virus (HIV) appears to increase their risk of certain types of cancer. Among these are primary lymphoma of the central nervous system, undifferentiated non-Hodgkin's lymphoma, squamous cell carcinoma, anorectal carcinoma, and cutaneous malignancies. These malignancies are similar in incidence to those seen in other immunodeficient patients. Lymphoma, in particular, is associated with a more aggressive disease state. In HIV-infected patients, the disease is usually diagnosed at a more advanced stage, frequently has extranodal involvement, and usually responds poorly to chemotherapy. Viruses, such as Epstein-Barr virus and papillomavirus, have been implicated in the pathogenesis of lymphoma and other malignancies in immunosuppressed patients, including those with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Treatment results with an aggressive chemotherapeutic regimen (MACOP-B) for intermediate- and some high-grade non-Hodgkin's lymphomas.

Seventy previously untreated patients with stage II, III, and IV intermediate- or high-grade lymphoma were treated with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between September 1985 and November 1987. Forty-nine of these patients had diffuse large-cell lymphoma (DLCL), and eight of these patients were human immunodeficiency virus (HIV)-positive. Complete responses were achieved in 54% of all patients and 52% of those with DLCL. With follow-up extending to 36 months, 45% of all DLCL patients are alive, and 50% are still living, if the HIV-positive patients are excluded from the analysis. Chemotherapy was quite toxic. Seventy-five percent of patients had severe mucositis, 42% had peripheral neuropathy, 50% required hospitalization, and 54% experienced leukopenia with a WBC count below 1,000/microL. Seven percent (five patients) died of toxicity related to the chemotherapy. Our analysis of prognostic parameters indicated that B symptoms, a performance status below 80, and, to a lesser extent, elevation of serum lactic acid dehydrogenase (LDH) (in HIV-negative DLCL patients) were associated with an inferior survival. Advanced age, sex, and bulky disease were not found to have a statistically significant effect on survival. Our preliminary results indicate that MACOP-B chemotherapy is an effective regimen for high- and intermediate-grade lymphomas. However, the survival for patients with DLCL treated with MACOP-B is no different than that achieved with previous regimens at our institution.

Adolescent↗
PubMed1990

A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: effects of tumor burden and antigen expression.

Eighteen patients with relapsed non-Hodgkin's lymphoma (NHL) were infused with escalating doses of monoclonal antibody (mAb) OKB7, trace-labeled with iodine-131 (131I), in order to study toxicity, pharmacology, antibody localization, and dosimetry of radioiodine. OKB7 is a noncytotoxic mouse immunoglobulin G2b (IgG2b) mAb reactive with B cells and most B-cell NHL. Three patients each were treated at six dose levels ranging from 0.1 mg to 40 mg. All patients had radionuclide imaging and counting daily, had serial blood sampling to study pharmacokinetics, human antimouse antibody (HAMA), and circulating antigen, and had a biopsy of accessible lymphoma to determine delivery of isotope to tumors and assess the effect of tumor antigen expression on mAb delivery. Bone marrow biopsies were also done in the majority of patients. There was no toxicity. Serum clearance showed a median early phase half-life of 1.9 hours and a later phase half-life of 21.7 hours. Median total body clearance half-life was 22 hours. Pharmacokinetics were not dose-related. HAMA was detected in five patients. Circulating blocking antigen was detected in the serum of four patients, but at levels that were of pharmacologic consequence only in one. Biopsied tumor tissue from five patients did not express OKB7 antigen. No significant uptake of antibody was seen in these tumor sites. Mean total uptake of isotope into lymphoma measured in biopsies correlated linearly over the 400-fold increase in injected mAb dose. However, the percent of injected dose found per gram of tumor was unrelated to dose, but correlated inversely with tumor burden. In two patients with minimal tumor burden, 1.0 mg and 5.0 mg doses of OKB7 resulted in tumor to body radioisotope dose ratios of 22 and 7, which would theoretically permit tolerable delivery of 4,400 and 1,400 rads to these tumors, respectively, if OKB7 were conjugated with higher doses of 131I.

Adult↗
PubMed1990

Prognostic factors among 185 adults with newly diagnosed advanced Hodgkin's disease treated with alternating potentially noncross-resistant chemotherapy and intermediate-dose radiation therapy.

The initial promising results with alternating chemotherapy regimens (mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine [MOPP/ABVD]; lomustine, melphalan, and vindesine [CAD] plus MOPP plus ABV) combined with intermediate-dose radiation therapy (RT) have been sustained with further follow-up; 82.2% of patients (152 of 185) achieved a complete remission (CR), and overall survival is 71.7% +/- 4.4% at 8 years (median follow-up is 55 months among the survivors). No statistically significant differences were found in CR percentage, CR duration, or survival between stages IIB, IIIB, and IV patients. For that reason, stepwise Cox regression analyses to identify the important prognostic factors were performed on overall survival, tumor mortality, freedom from disease progression, and survival following disease progression. Pretreatment characteristics were also tested for association with the probability of achieving CR, CR duration, and death due to other causes. Characteristics that were consistently associated with an independently unfavorable prognosis were low hematocrit, high serum lactic acid dehydrogenase (LDH), age more than 45 years, inguinal node involvement, mediastinal mass greater than .45 of the thoracic diameter, and bone marrow involvement. Patients with two or more unfavorable characteristics were much more likely to fail treatment (median survival, 62.4 months) than those with none or only one unfavorable factor (greater than 95% survival). This striking difference between the low- and high-risk groups remained even if the comparison was restricted to patients less than or equal to 45 years of age. These results provide a basis for selecting the young patients at high risk of failure for more intensive initial treatment with either autologous bone marrow rescue or hematopoietic growth factors.

Adult↗
PubMed1989

CT of primary lymphoma of the liver.

Primary lymphoma of the liver is a rare disease. In each of six cases, a large, often poorly defined mass of low attenuation was present within the liver. Four lesions originated in the right lobe and two originated in the left lobe. Satellite nodules were seen at presentation in one case and developed after presentation in two others. Other features, such as enhancement after contrast administration, necrosis, and calcification, were variable. Three of six lesions had areas of very low density, suggestive of necrosis. One mass had calcifications. After IV contrast administration, no enhancement occurred in three tumors, patchy enhancement occurred in two, and an enhancing ring was seen in the remaining tumor. The radiologic presentation of primary lymphoma of the liver differs from that of secondary involvement of the liver in systemic lymphoma. Whereas secondary lymphoma is often diffusely infiltrative and difficult to detect on CT, the lesions of primary lymphoma of the liver are easily identified on CT scans even before the administration of IV contrast material. Although rare, primary lymphoma of the liver should be included in the differential diagnosis of a large, hypodense liver mass on CT.

Adult↗
PubMed1989

Treatment of advanced Hodgkin's disease.

MOPP chemotherapy was the significant breakthrough that improved the outlook for patients with advanced Hodgkin's disease. Results with alternating potentially non-cross-resistant drug combinations, including MOPP/ABVD, CAD/MOPP/ABV, and MOPP/ABV, are similar and seem to be slightly superior to those with MOPP alone. Limited adjuvant RT does not seem to add appreciably to the morbidity of chemotherapy, although its role in improving on results with chemotherapy alone has not been well studied in prospective, randomized, controlled clinical trials. There are two major challenges for the future. The first is to improve the outcome for advanced Hodgkin's disease patients, perhaps with more intensive chemotherapy and RT with use of cytokines such as the colony-stimulating factors or interleukin-1 or with rescue employing autologous bone marrow transplantation or both. The second challenge is to reduce the morbidity but not the effectiveness of treatment for advanced Hodgkin's disease patients without adverse prognostic factors.

Adolescent↗
PubMed1988

Primary lymphoma of the spleen. Clinical features and outcome after splenectomy.

A retrospective review was made of patients with primary splenic non-Hodgkin's lymphoma (PSL) diagnosed at surgery at Memorial Hospital between 1970 and 1981. Four patients had splenic involvement only (Group I), three patients had splenic and splenic hilar nodal involvement (Group II), and 14 had involvement of the spleen and other sites including liver (11 patients), bone marrow (eight patients), and distant abdominal lymph nodes (five patients) (Group III). Three of the seven Group I and II patients are alive without disease at 24, 42, and 144 months. There was a trend toward a longer survival for the Group I and II patients as compared with the Group III patients. Patients with truely localized PSL seem to have the same outlook as other Stage I non-Hodgkin's lymphoma patients.

Adolescent↗