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Biomedical subjects

D J Straus

Publications and source records attributed to D J Straus.

At least 73 records · Page 4Linked to original sources

The non-Hodgkin's lymphomas. I. A retrospective clinical and pathologic analysis of 499 cases diagnosed between 1958 and 1969.

A retrospective clinical and histopathological review was made of 499 previously untreated cases of non-Hodgkin's lymphoma with adequate initial biopsy material diagnosed at Memorial Hospital between 1958 and 1969. Three hundred-eighty-four cases (77%) had diffuse, 104 (21%) nodular, nine (2%) nodular and diffuse, and two (less than 1%) unclassifiable histologic types. Overall median survival was 16 months, and 79% of the patients died with lymphoma. For all treatments, survival of responding patients was the same as that of nonresponders, a reflection of the palliative approach. Significant differences in survival were found between patients in the various Ann Arbor stages. Median survival was 42 months for the nodular group and 11.5 months for the diffuse (P less than 0.001). The ten-year survival was 12% for the diffuse and 22% for the nodular patients. The overall difference in survival was due to early deaths in the diffuse group. Long-term follow-up is necessary to appreciate the usual fatal course of patients with all types of non-Hodgkin's lymphomas treated conservatively.

Adolescent↗

Combination chemotherapy for the treatment of Hodgkin's disease in relapse. Results with lomustine (CCNU), melphalan (Alkeran), and vindesine (DVA) alone (CAD) and in alternation with MOPP and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV).

Vindesine (desacetyl vinblastine amide sulfate, DVA) was used in combination with CCNU (lomustine) and melphalan (Alkeran) (CAD) to treat 15 heavily pretreated patients with Hodgkin's disease in relapse. The patients were treated with up to six cycles, depending upon their response. Two patients (13%) achieved a complete remission (CR) and five (33%) patients a partial remission (PR). The major toxicity was prolonged thrombocytopenia, which was decreased by a reduction in the initial drug doses for patients who had received extensive prior chemotherapy and radiotherapy (RT). The CAD regimen was then alternated with nitrogen mustard or cyclophosphamide, vincristine, procarbazine, and prednisone (MOPP, C-MOPP) and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV) for a total of nine cycles in 25 patients with Hodgkin's disease in relapse with somewhat more favorable prognostic features. Two patients also received low-dose RT to areas of bulky nodal disease. Eleven patients (44%) achieved a CR and seven (28%) a PR. Of the 11 CR patients, six remain in remission. The serious toxicity was comparable to that seen with other combination chemotherapy regimens. These results indicated that the CAD/MOPP/ABVD regimen is as active as other so-called 'salvage' regimens for Hodgkin's disease in relapse, and suggest that it might be useful for newly diagnosed Hodgkin's disease.

Adolescent↗

Treatment of acute lymphoblastic leukemia in adults: results of the L-10 and L-10M protocols.

Two successive protocols (L-10 and L-10M) employing multidrug induction therapy with vincristine, prednisone, and doxorubicin (Adriamycin) plus an intensive consolidation phase and maintenance program have led to a significant improvement in the prognosis of adult acute lymphoblastic leukemia (ALL). The complete remission (CR) rates for the 34 patients entered on the L-10 protocol and the 38 patients entered on the L-10M protocol were 85% and 84%, respectively. The median duration of remission has not yet been reached for either the L-10 (median follow-up, 5.5 years; range, 3.5-7.5 years) or the L-10M protocol (median follow-up, 2.5 years; range, 1-3.5 years). The median survival time has not yet been reached for the L-10M protocol. Central nervous system prophylaxis with intrathecal methotrexate alone was effective in preventing central nervous system relapse. An analysis of possible prognostic factors indicated that patients less than 25 years of age had a higher CR rate than older patients (p = 0.02). Patients with an initial leukocyte count below 15,000/microL experienced longer remissions than patients with a leukocyte count above 15,000/microL (p = 0.008), and patients who achieved CR within the first month of therapy were in remission longer than those requiring a longer time to achieve CR (p = 0.04). Patients with T cell ALL did not have a poorer prognosis than other patients treated on these protocols. The L-10 and L-10M protocols were well tolerated with minimal morbidity.

Adolescent↗

Treatment of advanced diffuse histiocytic lymphoma: an analysis of prognostic variables.

Sixty-five patients with Stages III and IV diffuse histiocytic lymphoma (DHL) were treated with two different and successive combination chemotherapy protocols. Twenty-seven patients were treated with the cyclophosphamide (CTX) L2 protocol, which included maintenance chemotherapy for three years. Thirty-eight patients received the NHL-3 program. Both protocols included radiotherapy (1350--4000 rad) to areas of initial bulky disease or persistent tumor, as well as central nervous system prophylaxis with intrathecal methotrexate or cytosine arabinoside in patients with bone marrow involvement. Two-year survival rates were 44 and 56%, respectively, for the CTX-L2 and NHL-3 protocols. Of the 65 patients, 59 were evaluable for response to therapy. The CTX-L2 produced a 58% total response (TR) rate, 39% complete (CR), and 19% partial (PR). The patients on NHL-3 achieved a TR rate of 82%, 33% CR, and 48% PR. The difference in TR was significant (P = 0.05), but in CR was not. Prior chemotherapy (P = 0.077) and serum lactic dehydrogenase (LDH) level above 500 U/liter (P = 0.01) significantly lessened the chances for achievement of a CR. However, sex, age, the presence of systemic symptoms, stage (III vs. IV), and prior RT were not found to be significantly related to CR rate. This analysis suggests that a high level of serum LDH characterizes a subgroup of patients with particularly aggressive DHL that requires a more intensive modality of treatment.

Adolescent↗

Multidisciplinary treatment of advanced Hodgkin's disease by an alternating chemotherapeutic regimen of MOPP/ABDV and low-dose radiation therapy restricted to originally bulky disease.

Ninety-one evaluable patients with advanced Hodgkin's disease (patients with stages IIB, IIIB, or IV disease and patients with IIIA disease who were greater than 35 years old or had mixed cellularity or lymphocyte depletion histology) received chemotherapy with MOPP and ABDV given in alternating months; radiation therapy (RT) (2000 rad in 2 weeks) was given during Month 5 of therapy to the previously untreated patients through ports that were limited to the originally bulky disease. The complete remission rates observed were: 88% in previously untreated patients, 69% in patients who had had prior RT but minimal chemotherapy, and 50% in patients who had had prior heavy chemotherapy. The actuarial relapse-free survival rates at 4 years, for patients who had complete remission, are: previously untreated, 84%; prior RT, 70%; and prior heavy chemotherapy, 30%. The total actuarial survival rates at 5 years for all 118 patients, evaluable and nonevaluable, who were entered in the study, are: previously untreated, 80%, prior RT, 57%; and prior heavy chemotherapy, 40%.

Adolescent↗

Combination chemotherapy for patients with relapsed malignant lymphoma using methyl-GAG and teniposide (VM-26).

We treated 45 patients with advanced malignant lymphoma, using a combination of methyl-GAG and teniposide (VM-26). All patients had received extensive prior treatment with combination chemotherapy with or without irradiation. Both methyl-GAG (600 mg/m2) and VM-26 (100 mg/m2) were administered on Days 1 and 8 of the treatment protocol and, in responding patients, every 2 weeks thereafter. Partial responses occurred in six of 12 patients with Hodgkin's disease and in ten of 31 patients with non-Hodgkin's lymphoma. The median duration of response for all patients was 3 1/2 months (range, 1 1/2-11). There were moderate toxic effects, including nausea, myalgia, weakness, and myelosuppression. Relative to our recent experience with methyl-GAG as a single agent, the addition of VM-26 to methyl-GAG did not produce a superior rate or duration of response in similar, heavily pretreated patient populations with malignant lymphoma; however, the combination caused considerably more myelotoxicity. We conclude that the use of VM-26 with methyl-GAG in this dose schedule offers no advantage over single-agent therapy. Methyl-GAG, when administered on a biweekly schedule, is effective and well-tolerated. This agent should be considered for incorporation into chemotherapy protocols for the therapy of previously untreated patients with malignant lymphoma.

Clinical Trials as Topic↗

Angioimmunoblastic lymphadenopathy: clinical spectrum of disease.

The clinical features of 13 patients with angioimmunoblastic lymphadenopathy were analyzed to determine prognostic factors and response to therapy. Eleven patients presented with sudden onset of fever, weight loss, generalized lymphadenopathy, and hepatosplenomegaly. Laboratory features included autoimmune hemolytic anemia and polyclonal hypergammaglobulinemia. Pulmonary involvement was seen in six cases and skin rash in four. Two patients had localized lymphadenopathy without systemic symptoms. Both are alive at 5.5 and 2.5 years, respectively, after diagnosis, although the latter patient has required intermittent prednisone for recurrent lymphadenopathy. An additional patient is alive on treatment for months following diagnosis. The remaining ten have died, nine of sepsis and one of cerebral hemorrhage. The immunosuppression and myelosuppression of combination chemotherapy may have hastened their deaths. An individualized, conservative treatment approach is recommended.

Aged↗

Osteonecrosis in patients with malignant lymphoma: a review of twenty-five cases.

A retrospective study of 25 patients with malignant lymphoma who had osteonecrosis of either the femoral or humeral head(s) was undertaken. The common factor present among all patients was the administration of intermittent steroid-containing combination chemotherapy. Seventeen Hodgkin's disease patients received chemotherapy predominantly consisting of an alkylating agent, vincristine, procarbazine, and moderate amounts of prednisone. The non-Hodgkin's lymphoma patients were on various moderate dosage steroid-containing protocols, except three who received prolonged high-dose steroid-containing chemotherapy regimens. Sixteen of the 17 Hodgkin's disease patients and five of the eight non-Hodgkin's lymphoma patients received radiotherapy to the bones that subsequently developed osteonecrosis. Two of the three non-Hodgkin's lymphoma patients who were not irradiated were treated with high-dose steroid-containing chemotherapy regimens. Symptoms developed in patients 12 months and 32 months after completion of chemotherapy and radiotherapy, respectively. Osteonecrosis was a long-term complication of treatment between 1970 and 1979 and occurred in 1.6% of the Hodgkin's disease and 0.12% of the non-Hodgkin's lymphoma patients treated. The authors conclude that the patients at highest risk for this complication are those who receive both radiotherapy to the affected bone(s) and intermittent steroid-containing multiple drug chemotherapy.

Adult↗

The treatment of advanced hodgkin's disease.

Between January, 1975, and December, 1978, 118 patients with advanced Hodgkin's disease were treated with 8 months of alternating MOPP and adriamycin, bleomycin, dacarbazine and vinblastine (ABDV) combined with 1 month of low-dose radiation therapy (2,000 rad) to areas initially involved with bulky disease. Among 57 evaluable previously-untreated patients, 50/57 (88%) achieved complete and 7/57 (12%) partial remissions. The estimated relapse rate among the complete responders was 16% at 36 months from date of remission. Toxicity was comparable to that of other combination chemotherapy regimens. These results are among the best reported for the treatment of patients with advanced Hodgkin's disease.

Adolescent↗

Treatment of acute leukemia in relapse with 4'(9-acridinylamino) methanesulfon-m-anisidide (AMSA) in combination with cytosine arabinoside and thioguanine.

Thirty-seven patients with acute leukemia in relapse were treated with a three-drug combination that included a 3- or 4-day course of AMSA with total doses ranging from 600 mg/m2 to 740 mg/m2 I.V., cytosine arabinoside 25 mg/m2 I.V. followed by 200 mg/m2 by continuous infusion daily for 5 days, and thioguanine 100 mg/m2 p.o. q 12h for 5 days. Eight of the 25 patients with acute nonlymphoblastic leukemia achieved a complete remission and 3 a partial remission. None of the five patients with acute lymphoblastic leukemia achieved a response and there was one partial remission in the seven patients with myelodysplastic syndrome or blastic CML. Reversible toxicity included nausea and vomiting (78%), alopecia (100%), pancytopenia (100%), mild stomatitis (63%), and hepatic dysfunction (24%). One patient developed seizures and cardiac arrhythmias. The activity of this combination in heavily treated patients with ANLL is comparable to that of the anthracycline-containing regimens, and its use in previously untreated patients with ANLL should now be explored.

Acute Disease↗

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma.

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl-GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.

Adult↗

The eight-drug/radiation therapy program (MOPP/ABDV/RT) for advanced Hodgkin's disease: a follow-up report.

Eighty-four evaluable patients with advanced Hodgkin's disease (Stages IIB, IIIA age greater than 35 or mixed cellularity or lymphocyte depletion histology, IIIB, IVA, and IVB) were treated with alternating monthly MOPP and Adriamycin, bleomycin, dacarbazine, and vinblastine (ABDV). Radiation therapy (RT), 2000 rads in two weeks, was given to areas of initial bulky disease in untreated patients. Complete remission (CR) rates were 80% for previously untreated, 65% for prior RT or minimal chemotherapy treated, and 50% for heavily pretreated patients. Among 49 previously untreated patients there were no primary treatment failures. The estimated two-year relapse rate for the CR group was 9%. The therapeutic effectiveness of this program may have been due to either or both of the following elements: (1) two non-cross-resistant drug combinations, (2) low dose adjuvant RT to initial sites of bulky disease. These early results are among the best reported for the treatment of advanced Hodgkin's disease.

Adolescent↗

The acute monocytic leukemias: multidisciplinary studies in 45 patients.

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

Adolescent↗

Fatal graft-versus-host disease following blood transfusion in Hodgkin's disease documented by HLA typing.

Fatal graft-versus-host disease (GVHD) developed in a patient with Hodgkin's disease treated with combined chemotherapy and radiotherapy following the transfusion of 2 U of packed red blood cells. Clinical features of the GVHD included the development of exfoliative dermatitis, progressive hepatic dysfunction, aplastic anemia, and finally progressive fatal pneumonia. GVHD was documented by skin biopsy and chimerism by HLA typing. The HLA phenotype of the patient's skin fibroblasts [A3, Bw44 (w4)/A2, B15 (w4)] was appropriate for parental haplotypes and probably represented her true HLA phenotype. Lymphocytes from the patient (peripheral blood and lymph node biopsy) were of a different HLA phenotype (A3; Bw35, w38, w4, w6; Cw4), which was inappropriate for parental HLA haplotypes but identical to the HLA phenotype of one of the blood donors. The HLA-DR typing of the patient's family and of the blood donor demonstrated that the patient and the donor probably were HLA-DR identical (DRw5/DRw6), although no B lymphocytes could be obtained from the patient for direct DR typing. We are currently irradiating all blood products administered to patients with Hodgkin's disease receiving intensive treatment. Further observations will be necessary to determine whether transfusions to other cancer patients with immunodeficiency states should be restricted to irradiated blood products.

Adolescent↗