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Biomedical subjects

R T Hoppe

Publications and source records attributed to R T Hoppe.

At least 163 records · Page 9Linked to original sources
PubMed1983

Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation.

Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values.

Adult↗
PubMed1983

Changes in T-cell subsets in patients with rheumatoid arthritis treated with total lymphoid irradiation.

Patients with intractable rheumatoid arthritis (RA) were treated with total lymphoid irradiation (TLI, 2000 rads). We previously reported long-lasting clinical improvement associated with marked suppression of in vitro lymphocyte function in this group. In an attempt to better understand the mechanism of immunosuppression and clinical changes observed after TLI, we studied in greater detail changes in peripheral blood T-cell subsets identified by monoclonal antibodies. Before TLI, RA patients had a higher percentage of Leu-3 (helper subset) cells and a lower percentage of Leu-2 (suppressor/cytotoxic subset) cells than normals. Immediately after TLI, the absolute numbers of both Leu-2 and Leu-3 cells were reduced by at least 90%. Within 6-12 weeks, the number of Leu-2 cells returned to the pretreatment levels, but the levels of Leu-3 cells remained depressed for months thereafter. The lack of repopulation of Leu-3 cells resulted in a marked increase in the ratio of Leu-2 to Leu-3 cells as compared to pretreatment values (1.73 +/- 0.23 vs 0.39 +/- 0.06), and in a decrease in the percentage and absolute number of total T (Leu-1 and Leu-4) cells. The failure of Leu-3 cells (which mediate predominantly helper/inducer functions) to repopulate the peripheral blood may contribute to the prolonged clinical immunosuppression observed after TLI. Similar changes in T-cell subsets were not observed in RA patients given remittive drugs or low doses (200 rads) of radiotherapy. Thus, TLI differs from other treatment modalities with regard to its prolonged selective effect on the Leu-3 subset.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1983

Treatment of intractable rheumatoid arthritis with total lymphoid irradiation (TLI): immunological and clinical changes.

Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation in a feasibility study. The mantle and the inverted Y fields were treated successively to a cumulative dose of 2000 rads. Nine of eleven patients showed at least a 35% improvement in three of four clinical parameters by six months and continued to maintain at least this level of improvement at their last observation points (13-28 months after TLI). There was a marked decrease in the percentage of total T cells and Leu-3 cells (helper), but an increase in the percentage of Leu-2 cells (suppressor/cytotoxic), resulting in a dramatic increase in the Leu-2/Leu-3 ratio. There was also a decrease in response to PHA, Con A and MLR.

Animals↗
PubMed1983

Histologic conversion in the non-Hodgkin's lymphomas.

Between July 1, 1971 and December 31, 1978, 150 patients with favorable subtypes of non-Hodgkin's lymphoma [nodular poorly differentiated lymphocytic (NLPD), nodular mixed, or diffuse well differentiated lymphocytic] were entered into prospective randomized clinical trials at Stanford University. Treatments included involved field, total lymphoid, or whole body irradiation, single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine and prednisone (CVP) or with cyclophosphamide, vincristine, procarbazine, and prednisone (C-MOPP), or various combinations of chemotherapy and irradiation. The initial complete response rate (CR) was 79%. Among patients who achieved a CR, 31% later relapsed. There were 78 patients who either failed to achieve a CR or achieved a CR and later relapsed. Histologic conversion (change from initially favorable to an unfavorable subtype of non-Hodgkin's lymphoma) was documented in 22/78 patients (28%). However, the actuarial risk for conversion was actually much greater (60% at 8 yr). The median time to documentation of conversion was 51 mo. The most common type of histologic conversion was from NLPD to diffuse histiocytic lymphoma. Documented histologic conversion was often associated with a more aggressive clinical behavior of the lymphoma, and the median survival after conversion was less than 1 yr. However, those patients who achieved a CR after conversion had a more favorable outcome (actuarial survival 75% at 5 yr). No specific risk factors predictive of histologic conversion could be identified.

Actuarial Analysis↗
PubMed1983

Extralymphatic involvement in diffuse non-Hodgkin's lymphoma.

Between 1961 and 1982, 543 patients with diffuse histiocytic, mixed, or undifferentiated lymphoma were treated at Stanford University, Stanford, Calif. Of this group, 281 (52%) had extralymphatic lesions and the 111 patients with stage IE and IIE disease were subjected to analysis. Most patients (94) had diffuse histiocytic lymphoma. Lymphangiography was performed in 77%, bone marrow biopsy in 91%, and diagnostic or staging laparotomy in 52% of the patients. All but five patients were treated with megavoltage irradiation and 35 patients received combination chemotherapy. Median follow-up was 4.0 years. Kaplan-Meier actuarial survival at five and 10 years was 46% and 36%, respectively. Freedom from relapse (FFR) at five years was 49% with no relapses beyond that point. The most common extralymphatic sites were the gastrointestinal tract, the head and neck region, and the lung. Prognosis could not be correlated with the specific sites of involvement. Patients with bulky disease (greater than 10 cm) or more than three sites of involvement had a significantly lower survival and FFR. There was no significant difference in outcome for patients treated with irradiation or combined modality therapy. Most patients (62%) relapsed in distant extralymphatic sites.

Actuarial Analysis↗
PubMed1982

Morphologic types of diffuse large-cell lymphoma.

One hundred eighty-seven patients with confirmed diffuse non-Hodgkin's lymphoma were selected from a consecutive series of 391 patients who were evaluated and treated at Stanford University Medical Center. Lymphomas with any degree of nodularity and diffuse lymphomas of "well-differentiated" and "poorly differentiated" lymphocytic type were excluded from this study. Each of four observers identified cases of diffuse large-cell lymphoma from the 187 cases and further subdivided these cases into six morphologic types in accordance with criteria proposed by Strauchen et al. Initial intraobserver and interobserver agreement was relatively low but was greatly enhanced when the initial six morphologic types were grouped as either follicular center-cell or nonfollicular center-cell types. When individual observer results were pooled, statistically significant differences were seen between survival of patients in these two groups, with the patients in the nonfollicular differences were seen between survival of patients in these two groups, with the patients in the nonfollicular center-cell group having a worse prognosis (P = 0.04). This effect of morphologic type appeared to be independent of pathologic stage. Mitotic counts did not correlate with survival.

Diagnosis, Differential↗
PubMed1982

Hodgkin's disease: a clinicopathologic study of 659 cases.

A large number of histologic and clinical parameters were assessed, tabulated and intercorrelated in 659 patients with Hodgkin's disease evaluated and treated at Stanford University Medical Center. Nodular sclerosis was the most common pattern (60%) and also had the best total survival, but lymphocyte predominance had the best relapse-free survival. While a number of histologic parameters showed a significant correlation with relapse-free survival, multivariate analysis showed that age, stage, and treatment were relatively more important. Of the histologic parameters, only the number of lymphocytes, fibroblasts, and amount of sclerosis remained significant after multivariate analysis. The positive correlation of sclerosis, negative correlation of the number of fibroblasts and lack of correlation of lacunar cells with relapse free survival in patients with nodular sclerosis suggested that the type of mesenchymal reaction was of prime importance in determining prognosis in that form of Hodgkin's disease. The number of lymphocytes did not independently affect prognosis in patients with nodular sclerosis but did so for the entire group. The cellular phase of nodular sclerosis was found to have an overall survival and some clinical features more akin to mixed cellularity Hodgkin's disease.

Adolescent↗
PubMed1982

Central nervous system involvement in non-Hodgkin's lymphoma: an analysis of 105 cases.

Records of 105 patients with central nervous system (CNS) lymphoma were analyzed in order to better define the incidence, setting, and management of CNS lymphoma and the role for CNS prophylaxis. Survival was best for patient under 30 years of age treated with whole-brain irradiation and intrathecal (IT) chemotherapy whose CNS involvement was an isolated event (median survival time, 1.8 years). Survival was worst for patients over 30 years of age whose CNS invasion occurred at a time of progressive systemic lymphoma (median time ten weeks if treated with whole-brain irradiation with or without IT chemotherapy). The risk of CNS invasion was greatest for those with lymphoblastic lymphoma. Among patients with Stage IIE, III, or IV histiocytic lymphoma, the risk of CNS involvement was greatest for those with progressive or relapsing disease or involvement of the testes, peripheral blood, or epidural space of the spinal cord.

Adult↗
PubMed1982

Subtypes of cutaneous T-cell lymphoma defined by expression of leu-1 and Ia.

Monoclonal antibodies were used to characterize immunohistologically the expression of cellular antigens in 25 patients with cutaneous T-cell lymphoma (CTCL). Although all cases expressed the Leu-2a-/Leu-3a+ immunophenotype characteristic of helper T cells, four subtypes were defined based on variable expression of Leu-1 and Ia. In individual patients, the immunophenotype was constant irrespective of body compartment sampled or interim therapy. Ia+ non T-cells typically constituted one-third of the cellular infiltrate. Along with neoplastic cells, Ia+/T6+ dendritic cells were observed within Pautrier microabscesses, dermis, and individually throughout the epidermis. It will be important to determine if different CTCL immunophenotypes represent different biologic subsets of disease or have prognostic relevance. Prospective studies will be facilitated by single- and double-label immunohistologic techniques that allow the simultaneous evaluation of cellular antigen expression and architectural detail.

Adult↗
PubMed1982

Successful murine tumor allotransplantation after total lymphoid irradiation.

C3H/Km (H-2k) mice were treated with fractionated total lymphoid irradiation (TLI) (17 x 200 rad) and then were inoculated with 3 x 10(6) tumor cells from the EMT6 tumor cell line derived from the BALB/c (H-2d) mouse. One group of mice also received an i.v. infusion of BALB/c bone marrow (3 x 10(7) cells). Tumors in control animals (no TLI) became palpable within 10 days after inoculation, but subsequent tumor regression was rapid, with complete disappearance in all animals by 23 days. Initial tumor growth was exponential in both groups of mice treated with TLI, but tumors regressed after 30 days in the animals treated with TLI alone. In the group treated with TLI and bone marrow infusion exponential tumor growth continued until pulmonary metastases developed and all animals died. The TLI-treated mouse provides a model for tumor allografting. Further development of this model may demonstrate its efficacy in human tumor xenotransplantation.

Animals↗
PubMed1982

The management of stage I--II Hodgkin's disease with irradiation alone or combined modality therapy: the Stanford experience.

At Stanford University, between 1968 and 1978, 230 patients with pathologic stage I--II Hodgkin's disease were treated on prospective clinical trials with either irradiation alone or irradiation followed by 6 cycles of adjuvant combination chemotherapy. The actuarial survival at 10 yr was 84% for patients in either treatment group. Freedom from relapse at 10 yr was 77% among patients treated with irradiation alone and 84% after treatment with combined modality therapy [p(Gehan) = 0.09]. Freedom from second relapse at 10 yr was 89% and 94%, respectively [p(Gehan) = 0.56]. Several prognostic factors were evaluated in order to identify patients at high risk for relapse or with poor ultimate survival after initial treatment with irradiation alone. Systemic symptoms, histologic subtype, age, and limited extranodal involvement (E-lesions) did not affect the prognosis of patients and failed to identify patients whose survival could be improved by the routine use of combined modality therapy. Patients with large mediastinal masses (mediastinal mass ratio greater than or equal to 1/3) had a significantly poorer freedom from relapse when treated with irradiation alone than when treated initially with combined modality therapy [45% versus 81% at 10 yr, p(Gehan) = 0.03). The 10-yr survival of these patients, however, was not significantly different (84% versus 74%). The implications of these observations on the management of patient with early stage Hodgkin's disease are discussed.

Adult↗
PubMed1982

The treatment of mycosis fungoides with ointment-based mechlorethamine.

The use of topical mechlorethamine hydrochloride in the treatment of skin disease has been restricted because of the frequent development of contact dermatitis. A series of 24 patients with mycosis fungoides in stages 1A (eight patients), 1B (15 patients), and 2 (one patient) were treated with ointment-based mechlorethamine, prepared by an anhydrous method. This preparation was therapeutically effective. Complete clearing occurred in 15 of 18 patients with active disease over evaluation periods of up to 27 months, and one patient had partial clearing. Two patients showed a partial relapse during their evaluation periods. The incidence of contact dermatitis was very low: 8% in individuals with a history of hypersensitivity to mechlorethamine and 0% in patients being exposed to the medication for the first time. This new preparation has been shown to be effective therapy for mycosis fungoides. Patient use is associated with minimal side effects.

Administration, Topical↗
PubMed1981

Non-Hodgkin's lymphoma presenting as thyroid enlargement.

From 1969 to 1978, 11 patients with non-Hodgkin's lymphoma presenting as thyroid enlargement were evaluated and treated in the Division of Radiation Therapy at Stanford University Hospital. All patients were staged with lymphangiogram and bone marrow biopsy. Eight patients had Stage I-II disease and three patients had Stage III-IV disease. The histologic pattern of the biopsies was diffuse in nine cases, and eight cases were classified as histiocytic lymphoma. All eight patients with Stage I or II disease were treated with irradiation. There is an 83.3% survival at three years and a 75% relapse-free survival at two years. No instance of local recurrence was observed in this group of patients. The three patients with Stage III or IV disease were treated by either irradiation or chemotherapy. Two relapsed within one year and died with disease; the third remained free of disease for nine years before relapse and died with disease six months later. High dose regional irradiation is the recommended treatment for patients with Stage I-II lymphoma of the thyroid.

Adult↗
PubMed1981

Treatment of intractable rheumatoid arthritis with total lymphoid irradiation.

Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweek mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

Antibodies, Monoclonal↗
PubMed1981

Female reproductive potential after treatment for Hodgkin's disease.

The probability of maintaining ovarian function, becoming pregnant, and delivering a normal child is important to young women anticipating successful therapy for Hodgkin's disease. In this study, reproductive function was retrospectively examined in 103 women 40 years old or younger who had undergone treatment for Hodgkin's disease with total-lymphoid irradiation (TLI) alone, combination chemotherapy, or combined TLI and chemotherapy. Infertility was directly related to gonadal exposure to therapy and to age at treatment. Twenty women became pregnant after receiving total-nodal irradiation or combination chemotherapy or both. No fetal wastage occurred, and no birth defects were seen in the 24 infants born to these women. Even after intensive treatment programs, women successfully treated for Hodgkin's disease have become pregnant and delivered phenotypically normal children.

Adolescent↗
PubMed1981

Hodgkin's disease at autopsy: 1972-1977.

The autopsies of 80 patients with Hodgkin's disease (HD) were reviewed. Nearly one-third of the patients died without evidence of HD at autopsy. Four patients died with clinically unsuspected HD. Infection was the most common cause of death but a significant number of patients died of complications of therapy, both benign and malignant, including five patients with hematologic or de novo lymphoid malignancies. There was wide histologic variation of HD at autopsy and many cases had a pleomorphic appearance with few of the typical features of Hodgkin's disease. Fibrous nodules interpreted as sites of eradicated HD were found in many organs, most commonly lymphoreticular. Nonfatal histopathologic effects of therapy were common and specifically assessed thyroid and gonads.

Adolescent↗