Leon Stutzman

Acute nephrotic syndrome as a manifestation of active Hodgkin's disease: Report of four cases and review of the literature

Abstract Four patients are described in whom an acute nephrotic syndrome was associated with clinical relapse of Hodgkins disease. In three there were multiple episodes of increased proteinuria, hypoalbuminemia and edema; each of these periods was associated with evidence of recurrent growth of Hodgkins tumor. The proteinuria was promptly relieved by effective treatment of the Hodgkins disease with either chemotherapy or local radiation therapy delivered to areas distant from the renal bed. The data in ten similar cases of Hodgkins disease associated with single episodes of an idiopathic nephrotic syndrome, previously reported, are summarized. In these unusual patients the nephrotic syndrome appears to be etiologically related to the presence of the Hodgkins tumor; removal or destruction of the tumor relieves the proteinuria. It is suggested that a substance originating in tumor damages the renal glomerular basement membrane, perhaps after combining in an antigen-antibody complex.

Fibrous dysplasia of the bone: Review of twenty-four cases

Abstract Twenty-four cases of fibrous dysplasia were studied and clinical features reviewed. Three cases of particular interest are presented in detail. In one, both pituitary gigantism (in addition to severe deformity of facial bones) and hyperthyroidism were present. In the other two, familial hyperparathyroidism and fibrous dysplasia were present, a combination not previously reported. These latter two cases suggest the possibility that hyperparathyroidism may be another endocrinopathy associated with fibrous dysplasia and that this syndrome may also be familial.

Long survival in Hodgkin's disease

Abstract The records of fifty-eight patients with Hodgkins disease who survived for ten or more years from the time of diagnosis are reviewed in detail. These patients had more localized disease and a more favorable distribution of histologic patterns on admission than patients who died of Hodgkins disease within ten years. However, neither these factors nor the treatment they received (principally, radiation therapy) are sufficient to explain their long survival. Host factors, possibly related to cellular immune mechanisms, appear to play a major role in determining in which patients remissions will be prolonged. Our data confirm the reports of others that the nodular sclerosis histologic type of Hodgkins disease has distinctive clinical features. This form of the disease occurs predominantly in young female subjects in whom mediastinal adenopathy uniformly develops during its course and in whom manifestations of Hodgkins disease are tolerated which usually preclude long survival. Complete clinical remission of ten years or more warrants consideration of the possibility that a patient may have been cured of his Hodgkins disease. Only three of twenty-three patients with such remissions have shown subsequent evidence of Hodgkins disease, during follow-up periods approaching forty years.

A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease

Five hundred and sixty‐six patients with either Stage III or IV Hodgkins disease were prospectively randomized to test whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine with procarbarine and prednisone. The combination of CCNU, vinblastine, procarbazine, and prednisone (CVPP) was shown to be a highly effective program with a complete response frequency of 69%. The use of CCNU as part of the induction program was also shown to be the most significant determinant of prolonged remissions (P = .025). Reduced vomiting and neurotoxicity, as well as the oral administration, were the chief advantages of the CVPP as compared with MOPP. These factors resulted in improved patient and physician compliance. The MVPP regimen was also shown to be a highly effective regimen with a complete response frequency of 73% in patients without prior exposure to chemotherapy. However, the induction regimens containing vinblastine were associated with a significantly higher frequency of fatal hematopoietic toxicities than the induction regimens containing vincristine (P = .05). This higher frequency was almost exclusively seen in the elderly or in patients previously treated with both chemotherapy and radiotherapy. At this time, the remission durations maintained by vinblastine with periodic reinforcement are longer when compared with vinblastine maintenance alone (P = .06), but there is no corresponding increase in survival.

A comparative study of a bcnu containing 4-drug program versus mopp versus 3-drug combinations in advanced Hodgkin's disease. A cooperative study by the cancer and leukemia group B

A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkins disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3‐drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4‐drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3‐drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4‐drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.

Staging Laparotomy and Splenectomy in Early Hodgkin's Disease No Therapeutic Benefit

In a prospective randomized study of treatment for early-stage Hodgkins disease presenting above the diaphragm, 76 patients had staging by laparotomy (Group I) and 28 had staging by closed techniques (Group II). Treatment consisted of involved-field radiotherapy alone (44 patients), involved-field radiotherapy followed by chemotherapy (38 patients), total nodal radiotherapy alone (15 patients), or total nodal radiotherapy followed by chemotherapy (seven patients). On presentation, both groups had similar clinical features and similar treatment distribution. With similar follow-up (87 months), no significant differences in remission or survival were observed between Groups I and II: remission 59 versus 68 percent; survival 74 versus 92 percent; p value 0.27 and 0.09, respectively. Multiple areas of relapse were more frequently observed in Group I (11 of 32 had relapse) as compared with Group II (none of nine had relapse, p less than 0.082). In Group I, relapse in the abdomen was observed as an isolated event or as part of disseminated relapse in 12 percent of patients compared with 3 percent (one patient) in Group II with abdominal relapse alone. Seven patients in Group I and two patients in Group II died with Hodgkins disease. Six other patients in Group I died with complete remission of non-Hodgkins lymphoma (one patient), leukoencephalopathy (one patient), sepsis during chemotherapy (two patients), myocardial infarction (one patient), and cerebrovascular accident (one patient). Three other patients in this group had other secondary malignancies successfully controlled (histiocytic lymphoma, squamous cell carcinoma of the cervix, and malignant schwannoma). No second primary lesions or death with complete remission were observed in Group II. Staging laparotomy with splenectomy in early-stage Hodgkins disease did not improve the duration of remission or survival or decrease the number of abdominal relapses compared with closed staging.

Correlation of delayed hypersensitivity responses with chemotherapeutic results in advanced Hodgkin's disease

Delayed skin test responses to several or all of a battery of six antigens were evaluated in 64 patients with disseminated Hodgkins disease before, during, and after multiple‐agent chemotherapy. Before therapy, 53% of patients had one or more positive skin tests, as compared to 55% during intensive chemotherapy, 79% during maintenance therapy, and 100% after discontinuation of all treatment, Pretreatment skin tests were of no value in predicting clinical response to chemotherapy. Response rates, duration of response, and survival were similar among anergic patients and patients with positive skin tests before treatment. There were too few patients who remained anergic after intensive induction chemotherapy to permit a correlation of immunologic reactivity with course. We conclude that skin test responses to recall antigens, before or during aggressive treatment, are more indicative of Hodgkins disease activity (and also, of the immunosuppressive effects of treatment routines) than of prognosis.

Lymphosarcoma. A comparison of extended to conservative chemotherapy

Sixty‐three patients with Stage III and IV lymphocytic lymphoma were randomized for induction treatment between a single course of nitrogen mustard and a 14‐day course of prednisone (conservative therapy) or sequential rotation of BCNU, nitrogen mustard and cytoxan with intermittent vincristine and prednisone for 6 months (extended therapy). Maintenance therapy by an oral alkylating agent (cytoxan or chlorambucil) with or without prednisone was given. Complete remission occurred in 75% of the conservative and 77% of the extended therapy group. The median duration of remission was similar, and greater than 27 months in both groups, and there was no difference in survival. At 1 year 80% of patients with no prior chemotherapy were in remission vs. 47% of patients with prior chemotherapy (p < .01). No significant advantage for extended chemotherapy was found. The addition of vincristine was not helpful in induction and prednisone during maintenance did not improve the duration of remission or survival.

Systemic mast cell disease: Physiologic considerations and report of a patient treated with nitrogen mustard

Abstract A case of systemic mast cell disease, a rare cause of unexplained hepatic and splenic enlargement, is presented. Although associated with urticaria pigmentosa, the significance of the skin lesions may be easily overlooked. Routine tissue sections may not allow recognition of mast cell infiltration; special stains are necessary when this condition is suspected. Definite but temporary improvement followed nitrogen mustard therapy, and no untoward pharmacologic reactions were seen. No histaminemia or increase in excretion of serotonin metabolites occurred during treatment. No histaminuria was noted. Hydrocortisone and prednisone therapy produced no clinical improvement, although heparinemia following large intravenous doses of hydrocortisone indicated mast cell degranulation or destruction. Tracer doses of S 35 were incorporated into mast cells as shown by radioautography. Its possible use in therapy has been considered, but rejected in this case because of potential risks to a patient whose clinical status was satisfactory.

Long term follow-up of combination chemotherapy--radiotherapy of Stage III Hodgkin's disease. A Cancer and Acute Leukemia Group B study

The Cancer and Acute Leukemia Group B studied the effect of combination chemotherapy‐radiotherapy on Stage III Hodgkins disease. Chemotherapy consisting of 4 weekly doses of vinblastine and one dose of mechlorethamine hydrochloride was followed by no therapy (CT), radiation to involved fields (CTIF) or total nodal radiation (CTTN). Two other treatment arms included total nodal radiation alone (TN) or total nodal radiation followed by chemotherapy (TNCT). Maximum follow‐up is ten years. Complete remission percentages were 36 (8/22) for CT, 71 (17/24) for CTIF, 100 (21/21) for CTTN, 86 (19/22) for TNCT and 89 (16/18) for TN. Disease‐free survival in patients receiving radiation ± chemotherapy is 23%(19/73) at 5 years, but even after 9 years relapses were observed in two patients. Forty‐one percent of all patients are alive and 32% have survived for five years. Ability to administer adequate therapy was the main determinant for response duration and survival. Factors influencing the outcome of the disease include histology, age, splenectomy, initial white blood cell count and performance status, whereas symptomatology, initial absolute lymphocyte count and sex played no role on survival.