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Biomedical subjects

R T Hoppe

Publications and source records attributed to R T Hoppe.

At least 109 records · Page 6Linked to original sources

Intercurrent death after Hodgkin disease therapy in radiotherapy and adjuvant MOPP trials.

STUDY OBJECTIVE: To assess long-term differences in mortality associated with initial Hodgkin disease therapy. DESIGN: Retrospective review of patients treated in prospectively randomized clinical trials. PATIENTS: Three hundred twenty-six patients with pathologic stage I, II, or III, A or B Hodgkin disease treated between 1967 and 1980 with median follow-up exceeding 14 years. INTERVENTIONS: Patients at the same stage of disease were randomized to receive radiation alone (167 patients) or radiation followed by 6 cycles of mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone (MOPP) chemotherapy (159 patients) with additional therapy for progression or recurrence. MEASUREMENTS AND MAIN RESULTS: No significant differences between treatment regimens for actuarial survival, intercurrent disease, or Hodgkin disease mortality were seen. Thirty-three patients who received radiation alone and 30 patients who received adjuvant chemotherapy died without evident Hodgkin disease. Death was caused by second neoplasms in 28 patients (relative risk, 2.35; 95% CI, 1.46 to 3.24). Six patients developed acute myelogenous leukemia or a myeloproliferative disorder after treatment including MOPP. Chemotherapy exposure varied among the 8 patients with lung cancers, 6 with gastrointestinal and 3 with other adenocarcinomas, 3 with sarcomas, 1 with diffuse large cell lymphoma, and 1 with melanoma. Acute myocardial infarction caused 9 of 17 cardiovascular disease deaths with 5 occurring in patients between the ages of 33 and 43. Nonetheless, the risk for acute myocardial infarction was not clearly increased (relative risk, 0.86; 95% CI, 0.42 to 1.57). Fifteen patients died from infection: 5, opportunistic; 5, asplenic sepsis; and 5, other pneumonias. Two patients died in accidents, and 1 died from radiation pneumonitis. CONCLUSIONS: Adjuvant MOPP chemotherapy improved freedom from relapse without significant survival benefit or impairment. Leukemogenesis was the only lethal complication associated with MOPP. Survivors of Hodgkin disease had an increased risk for death from a second neoplasm, but no apparent increased risk for death from acute myocardial infarction.

Actuarial Analysis↗

Nodular and diffuse types of lymphocyte predominance Hodgkin's disease.

The nodular form of lymphocyte predominance Hodgkin's disease has been shown to be immunophenotypically distinct from the histologically diffuse form and from other types of Hodgkin's disease. We undertook a clinicopathological study of 73 cases to determine whether any clinical differences between the nodular and diffuse subtypes could be discerned. Patients with the diffuse form (n = 41) tended to have a course similar to that of other types of Hodgkin's disease; there were few relapses and only two deaths due to Hodgkin's disease. In contrast, patients with the nodular form (n = 32) had significantly more relapses, which were independent of stage or treatment and equally distributed up to 10 years after initial therapy. Despite the frequent relapses, patients with the nodular form had an indolent course, and there was only one death due to Hodgkin's disease. There were seven fatal second cancers and two non-neoplastic treatment-related deaths, equally distributed between the nodular and diffuse groups. We conclude that nodular lymphocyte predominance Hodgkin's disease may have important clinical as well as immunophenotypic differences from other forms of Hodgkin's disease, and that patients with this condition should be followed carefully because of the possibility of late relapse.

Adolescent↗

Dissection of the mechanisms of immune injury in rheumatoid arthritis, using total lymphoid irradiation.

Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation. After radiotherapy, there was a marked decrease in the number and function of peripheral blood helper/inducer (Leu-3+) T lymphocytes, in the spontaneous secretion of interleukin-1 by synovial biopsy specimens, and in the activity of the joint disease. In contrast, levels of IgM, IgA, and IgG rheumatoid factors and C3 concentrations in blood and synovial fluid samples did not change significantly after therapy with total lymphoid irradiation.

Arthritis, Rheumatoid↗

Treatment of lupus nephritis with total lymphoid irradiation. Observations during a 12-79-month followup.

Seventeen patients with intractable lupus nephritis and nephrotic syndrome were treated with total lymphoid irradiation. Statistically significant improvement in mean renal disease and serologic activity parameters occurred within 3 months and persisted for at least 3 years. Although there was a marked reduction of T helper cell numbers and function after total lymphoid irradiation, recovery of these parameters was not associated with a return of disease activity. Risks of sterility, severe infections, and hematologic malignancy appeared to be lower than with alkylating agents.

Adolescent↗

Combined modality therapy for stage I-II large cell lymphoma.

Between January 1978 and December 1986, 94 patients with Stage I-II large cell lymphoma were evaluated at Stanford University Medical Center and treated with a combination of chemotherapy (CTX) and irradiation (XRT). The predominant histology was diffuse large cell (78), followed by immunoblastic (7), follicular large cell (6), and diffuse mixed small and large cell lymphoma (3). Twenty-three patients had Stage I and 71 had Stage II disease. Fifty-one had extranodal involvement (13 IE, 38 IIE), and 11 had B symptoms (2 IB, 9 IIB). Lymphoma was supradiaphragmatic in 58 patients, infradiaphragmatic in 21, and only in extranodal sites in 15. Patients received either involved (81) or extended (13) field XRT with a median dose of 40 Gy and combination CTX with 2 to 9 cycles (median 6) of either CHOP (68), M-BACOD (8), C-MOPP (8), MACOP-B (4), or other (6). Seventy-two patients remain with no evidence of disease, 21 are dead with disease, and one suffered an intercurrent death. Among the 19 patients who relapsed, there were six failures within the XRT field only, two within and outside the XRT field, and 11 outside of the XRT fields only. Actuarial survival and freedom from relapse (FFR) for the entire population were 74% and 72% at 5-years, respectively (33 month median follow-up). Stage I patients achieved 81% survival and 78% FFR, and Stage II patients had 72% survival and 70% FFR. In univariate and multivariate analyses, a favorable outcome was associated with the CTX-XRT-CTX sequence of therapy (p = 0.001), low LDH (p = 0.01), and small tumor bulk (p = 0.04). There were no relapses or deaths among the 21 patients receiving the "sandwich" sequence (CTX-XRT-CTX) of therapy. This series may serve as a comparison with single modality treatment programs for localized large cell lymphoma using either XRT or CTX alone.

Actuarial Analysis↗

Benign and malignant forms of erythroderma: cutaneous immunophenotypic characteristics.

In order to determine if immunohistologic features are useful in distinguishing benign from malignant types of erythroderma, we studied the immunophenotype of lesional T cells in 20 patients (8 mycosis fungoides/Sézary syndrome, 12 benign) and found them to be generally similar. In all cases, the majority of T cells were Leu-1+, Leu-4+, and Leu-5+, as is typical of mature T cells. Although in most cases a majority of Leu-3+ (helper/phenotype) T cells were present, in 2 there was a majority of the Leu-2+ (cytotoxic/suppressor) subset and in 12 others, a significant minority (20%-40%) of these cells. Low percentages of Leu-2+ cells (less than or equal to 10%), resulting in high Leu-3+/Leu-2+ ratios, did not distinguish benign from malignant erythroderma. Leu-8 antigen deficiency was common in both mycosis fungoides/Sézary syndrome and benign cases (62% vs 75%, respectively). In contrast, Leu-9 antigen deficiency was present in only one patient in each group. The lack of combined Leu-8/9 antigen deficiency in our patients may be due to a heavy inflammatory T cell component, obscuring the antigen deficiencies seen in most nonerythrodermic mycosis fungoides cases. We conclude that immunophenotypic studies with the use of the current antibody panel show many similarities between benign and malignant forms of erythroderma, as well as some minor differences that may prove diagnostically useful if corroborated by future studies.

Antibodies, Monoclonal↗

Clinical and immunological studies of cadaveric renal transplant recipients given total-lymphoid irradiation and maintained on low-dose prednisone.

Twenty-five recipients of cadaveric renal transplants were given total lymphoid irradiation (TLI), perioperative antithymocyte globulin, and low-dose prednisone as the sole maintenance immunosuppressive drug. Nine patients were diabetic, and follow-up was between 19 and 37 months. One-year graft and patient survival was 76% and 87%, respectively, Serious complications included four deaths from cardiovascular disorders, and two deaths from viral infections. Studies of peripheral blood T cell subsets showed a prolonged reduction in the absolute number of helper (Leu-3+) cells, and a rapid recovery of cytotoxic/suppressor (Leu-2+) cells. Analysis of the latter subset, using the monoclonal antibody 9.3, showed that the ratio of suppressor/cytotoxic cells was approximately 10:1. The normal ratio is 1:1. The mean mixed leukocyte reaction remained below 30% of the pre-TLI value for 6 months, and approached 80% at two years. Similar kinetics were observed in the proliferative response to mitogens. The results show that maintenance immunosuppressive drug therapy can be reduced after TLI as compared with conventional drug regimens that use prednisone in combination with cyclosporine and/or azathioprine.

Adult↗

Vinblastine, bleomycin, and methotrexate: an effective adjuvant in favorable Hodgkin's disease.

Sixty-seven patients with favorable pathologic stage (PS) I and IIA or B or IIIA Hodgkin's disease were randomized to receive subtotal or total lymphoid irradiation (STLI/TLI) alone or involved field irradiation (IF) plus six cycles of a novel adjuvant chemotherapy containing vinblastine, bleomycin, and methotrexate (VBM). With a follow-up from 6 to 72 months (median, 37 months), the actuarial freedom-from-progressive disease (FFP) at 5 years is 70% after STLI/TLI and 95% after IF plus VBM. One death has occurred in the irradiation-only treatment group. The data for IF plus VBM are significantly superior to previous actuarial results at 5 years using IF alone (FFP = 35%, P less than .00001) and compare favorably with prior results with IF plus nitrogen mustard, vincristine, procarbazine, +/- prednisone (MOP[P]) chemotherapy (FFP = 80% at 5 years, P = .10). VBM is well tolerated with greater than 90% of calculated doses delivered. As anticipated, VBM has had relatively little adverse effect on male or female fertility. Selected pulmonary functions are reduced early after IF plus VBM to a greater degree than with irradiation of the mediastinum alone, but the differences are modest. Based upon our current numbers and follow-up, we can be 90% confident that VBM as an adjuvant to irradiation in favorable Hodgkin's disease is as effective, or even superior, to MOP(P) chemotherapy. Because of its lesser toxicity, adjuvant VBM may have a broader role in the management of Hodgkin's disease.

Adult↗

Clonal rearrangement of the T cell receptor beta gene in the circulating lymphocytes of erythrodermic follicular mucinosis.

Follicular mucinosis is a condition characterized by the abnormal accumulation of acidic mucopolysaccharides in hair follicles. It is classically described as occurring idiopathically in young persons and within the infiltrates of mycosis fungoides in older individuals. We report a 12-year-old girl who had erythrodermic follicular mucinosis, hypereosinophilia, circulating Sezary cells, and both immunophenotypic and genotypic evidence of T cell neoplasia. Erythrodermic follicular mucinosis may represent an unusual variant of the Sezary syndrome, which to date has not been described in children or adolescents.

Alopecia↗

Poikilodermatous mycosis fungoides and atrophic large-plaque parapsoriasis exhibit similar abnormalities of T-cell antigen expression.

We studied the immunohistologic findings of skin biopsy specimens from 21 patients with poikiloderma (14 with mycosis fungoides [MF] and seven with atrophic large-plaque parapsoriasis [ALPP]). Both types of poikiloderma were similar with regard to T-cell antigen expression. In each case, most T cells expressed the CD4+ (helper/inducer) phenotype and lacked Leu-8 antigen. T cells were also deficient in Leu-9 antigen in most cases (MF, 11/14 [79%]; ALPP, 4/7 [57%]). These T-cell antigen deficiencies are similar to those described previously in various types of MF and indicate that such deficiencies are common in minimally infiltrated, patch-stage MF lesions. Because combined Leu-8/Leu-9 antigen deficiencies are uncommon in inflammatory skin diseases, our findings are consistent with the view that ALPP is an early form of MF, as had been suggested previously by results of clinicopathologic studies.

Adult↗

Extracutaneous mycosis fungoides.

The clinical course of 40 patients with histologically documented extracutaneous mycosis fungoides (ECMF) was reviewed. Thirty one patients had documentation of nodal disease only (Stage IVA). Nine patients had histologic evidence of visceral involvement (Stage IVB). A wide variety of topical, regional and/or systemic therapies were used in the management of these patients. The median survival for the entire group was 14.5 months. Eleven patients (28%) obtained a complete response (CR) and had a median survival of 21 months as compared with 8 months among 29 patients not obtaining a CR. One patient is without evidence of disease (NED) at 10 years. Multiple prognostic factors were examined with respect to survival. Prognostic factors found to be significant at the P = 0.05 level included ECMF at presentation of skin disease (versus at the time of relapse), the ability to achieve a CR, and management incorporating the use of topical therapy, especially electron beam treatment. Tabulation of all trials of chemotherapy either at diagnosis of ECMF or subsequently revealed that cyclophosphamide, vincristine and prednisone (CVP) and cyclophosphamide, vincristine, prednisone, and bleomycin (COP-Bleo) were the most effective chemotherapeutic combinations. In a multivariate analysis with survival as the endpoint, the best model consisted of only two covariates: ECMF at presentation of skin disease, and the use of topical therapy. Other covariates found not to be significant at the P = 0.05 level included age, gender, clinical extent of cutaneous and extracutaneous disease, Stage IVA versus Stage IVB disease, the presence of Sezary cells in the peripheral blood smear, and management incorporating the use of systemic therapy.

Adult↗

Long-term followup of rheumatoid arthritis patients treated with total lymphoid irradiation.

Total lymphoid irradiation was administered to 32 patients with intractable rheumatoid arthritis. Twenty-four patients showed at least a 25% improvement in 3 of 4 disease activity parameters, which persisted during the followup period of up to 48 months. Eight of the 32 patients required adjunctive immunosuppressive drug therapy to maintain improvement. Four patients died after total lymphoid irradiation; the causes of death were acute myocardial infarction (1 patient), pulmonary embolism (1 patient), and rheumatoid lung disease complicated by respiratory infection (2 patients). After therapy, patients exhibited a prolonged reduction in the number and function of circulating T helper cells.

Aged↗

Minimal long-term cardiopulmonary dysfunction following treatment for Hodgkin's disease.

UNLABELLED: We studied the long term cardiopulmonary function, at rest and during exercise, of 57 patients who were at least 1 year (mean 5 years) post-treatment for Hodgkin's disease. To establish the maximum degree of dysfunction we studied 40 patients who had extensive intrathoracic disease treated with radiotherapy alone (Exten-X; n = 20) or combined modality therapy (Exten-XC; n = 20). Patients without intrathoracic disease given either prophylactic mantle therapy (Proph-X, n = 10) or no chest irradiation ( CONTROL: n = 7) were used as controls. An abnormal electrocardiogram, by virtue of a conduction defect, was observed in seven patients, six in the Exten-X or Exten-XC groups. Borderline abnormalities including ST-T changes, prolonged QT interval, or axis deviation occurred in 14 patients distributed evenly throughout the groups. Resting mean pulmonary function test values were normal in all treatment groups. Exercise tolerance, as indicated by peak oxygen consumption (VO2), was significantly lower for the Exten-XC group compared to Proph-X (p less than 0.01). However, the mean value of VO2 for group Exten-XC was only 15% below that predicted. Of the 12 patients with abnormally low VO2 (greater than 20% below their predicted value), 11 were in the Exten-X or Exten-XC group with no difference between the two groups. Patients who received radiotherapy to at least one lung field, using either the thin lung block technique or open field irradiation, had significantly lower exercise tolerance than those treated with full thickness blocks (p less than 0.05). Despite these abnormalities only a single patient complained of marked dyspnea. We conclude that extensive treatment to the mantle field, especially when followed by chemotherapy in patients with extensive intrathoracic Hodgkin's disease, can result in minimal cardiopulmonary dysfunction in approximately one-third of patients.

Adolescent↗

Mycosis fungoides: management with topical nitrogen mustard.

The technique of treatment, response rate, freedom from relapse, survival, and complications of therapy in 123 patients treated with topical nitrogen mustard (HN2) for cutaneous mycosis fungoides (MF) at Stanford University Medical Center are reviewed. Patients were treated with HN2 in an aqueous or ointment base with equal efficacy. Response rates depended on the extent of skin involvement. In limited plaque (T1) disease, complete and overall response rates were 51% and 88%, respectively, while in generalized plaque (T2) disease they were 26% and 69%. No patients with tumorous involvement (T3) achieved complete skin clearance and all 13 of these patients developed progression of disease. Only two of nine patients with erythrodema (T4) achieved a complete response (CR), and both later relapsed. After achieving a CR, 40% of patients with T1 disease and 60% with T2 disease later relapsed; however, subsequent therapies, including repeat courses of topical HN2, often were successful in achieving later skin clearance. Overall, 42% of T1 patients and 31% of T2 patients were without evidence of MF at last follow-up. When death occurred, it was usually unrelated to MF in the T1 group. However, half of the deaths of patients with T2 disease were attributable to MF. Among the 22 patients with T3 or T4 disease, 80% of deaths were attributable to MF. The most common complication observed was a cutaneous hypersensitivity reaction, which occurred much more commonly with the aqueous than the ointment preparation. Fourteen patients (11%) developed subsequent cutaneous malignancies.

Adult↗

Solitary plasmacytoma of bone: treatment, progression, and survival.

Twenty patients with solitary plasmacytoma of bone were treated by radiation therapy. Local control was achieved in 19 and most patients developed systemic myeloma. To evaluate disease progression, 65 patients, including 45 from published series, were analyzed. Younger patients seemed less likely to progress (P = .06), but other clinical characteristics including site of involvement and paraprotein status did not influence progression. After dissemination, patients had a clinical course similar to patients with stage I myeloma, with a median survival of 47 months. Overall, patients with solitary plasmacytoma of bone had an indolent course of disease, with a median survival of 10.7 years and a 5-, 10-, and 20-year survival of 75%, 52%, and 37%, respectively.

Adult↗