Splenectomy for palliation of chronic myelocytic leukemia.

Sixty patients with chronic myelocytic leukemia (CML) (most, in the "terminal phase" of the disease) were subjected to splenectomy because of symptomatic splenomegaly, thrombocytopenia or anemia for which they required frequent transfusions. Surgical morbidity and mortality were high when the procedure was performed on a "casual" basis, but both were reduced sharply after care of these patients was restricted to a single medical-surgical-nursing team and improved technics of surgery and perioperative management were developed. Significant hematologic and clinical benefit was achieved in half of the patients and temporary arrest of the disease was often observed, but in most patients, the basic evolution of CML was not greatly altered. In eight patients, however, long-lasting improvement (one to nine years) was recorded. Measurement of the doubling time of circulating leukemic cells and other observations were consistent with the hypothesis that, in some patients, the spleen contains a more rapidly proliferating and "more malignant" population of leukemic cells than the marrow. We conclude that splenectomy is often a useful palliative procedure in advanced stages of CML, and that it may be strikingly beneficial in 10 to 15 per cent of such cases.     

Graft-versus-host reaction following blood product transfusion

The observation of graft-versus-host (GVH) reaction after platelet transfusion in a patient with Hodgkin's disease led us to analyze 38 reported cases in the literature, to outline prognostic factors and to characterize patients at risk. Overall mortality was 68 percent. It was higher among children (76 percent) than among adults (62 percent), and among patients with Hodgkin's disease and immune deficiency syndromes (88 percent) than among those with leukemias (23 percent, p < 0.005). Following blood transfusions from normal donors, mortality was higher (88 percent) than after transfusions from donors with chronic myelocytic leukemia (25 percent, p < 0.05). Minimal lymphocyte doses necessary to cause GVH reaction are in excess of 10⁷/kg. Adults seem more resistant to homografts than do children, and the host's cellular immune status is of major prognostic importance. Lymphocytes from donors with chronic myelocytic leukemia may be deficient, and after a threshold dose, the number of lymphocytes transfused does not correlate with clinical outcome. Effective prophylactic measures do exist for this complication but satisfactory therapy does not.     

Fibroblast interferon treatment of a patient with chronic active hepatitis. Increased number of circulating T lymphocytes and elimination of rosette-inhibitory factor.

A 23 year old woman with chronic active hepatitis documented by liver biopsy demonstrated persistent hepatitis B surface antigen, hepatitis B virus specific DNA polymerase hepatitis B core antigen (HBcAg), for approximately one year. The number of circulating T lymphocytes that rosetted with sheep erythrocytes was decreased, and a rosette-inhibitory factor was present in her peripheral blood. Interferon treatment (1 X 10(6) U/day intramuscularly for 82 days) resulted in a decrease of HBsAg and disappearance of HBcAg, (HBeAg) and specific DNA polymerase. In addition, the number of T lymphocytes increased to normal, and the rosette-inhibitory factor disappeared from the circulation. These findings suggest that the effect of interferon in chronic active hepatitis is mediated in part through its action on the immune system.     

In vitro leukocyte thymidine uptake and prognosis in chronic lymphocytic leukemia.

Among 60 patients with chronic lymphocytic leukemia, higher in vitro uptake of tritiated (3H) thymidine by leukocytes of a standard volume of peripheral blood was associated with a higher lymphocyte count, a more advanced stage, greater frequency of functional impairment and shorter survival. Appropriate analyses demonstrated that leukocyte thymidine uptake correlated with survival independently of these other disease features. Relative thymidine uptake (radioactivity per 10(3) lymphocytes) did not prove to be a useful prognostic parameter. Among 33 patients not receiving antileukemic therapy at the time of study, 15 of 17 (88 per cent) of those with higher thymidine uptake values, but only 3 of 16 (19 per cent) of those with lower values, were treated during a median follow-up period of four and a half years (p less than 0.001). Seven of the former group, but none of the latter group, died during the first three years of follow-up (p less than 0.01). We conclude that thymidine uptake by circulating leukocytes constitutes a relatively accurate index of the proliferating leukemic cell mass in this disease and provides useful prognostic information.     

Chromosome analysis in hematologic disorders: The leukemias

For two decades, cytogenetic studies have been used to rule in (or out) the Philadelphia (Ph¹) chromosome associated with chronic myeloid leukemia. Beyond this single purpose, chromosome studies have generally not been utilized in or applied to the practice of hematology-oncology. This report presents male and female patients, teens to 70s in age, with representative hematologic disorders, in whom the cytogenetic findings were useful clinically. These cases illustrate the following principles: (1) hematologic disorders can be characterized by chromosome analysis; (2) chromosome findings help in the diagnosis, prognosis, and treatment of blood diseases; (3) blood and bone marrow samples can be processed routinely for cytogenetic analysis; (4) these samples can be transported long distances from clinic to laboratory; and (5) the contemporary practice of hematology and oncology requires chromosome analysis for fuller evaluation and understanding of hematologic conditions.     

Morbidity of staging laparotomy in Hodgkin's disease

The morbidity of exploratory laparotomy and splenectomy in Hodgkin's disease was determined at three institutions—a university hospital, a major university affiliated hospital and a large community hospital. Of the 90 patients who underwent exploratory laparotomy, 33 (37 per cent) sustained a major or minor complication within two weeks of surgery. Seventeen patients (19 per cent) sustained a minor complication and 16 patients (18 per cent) a major complication. There was no mortality. A higher complication rate occurred in patients more than 28 years of age (p = 0.01), and in patients with advanced clinical stage when age was controlled (p = 0.05). We suggest that prior to performing an exploratory laparotomy in a given patient, the necessity of the procedure be weighed against its potential hazards.     

Gaucher's disease associated with Hodgkin's disease

A patient with chronic adult-onset Gaucher's disease is described. The diagnosis was based on the finding of typical Gaucher cells in the spleen, liver and bone marrow associated with deficiency of glucocerebrosidase. The patient also had Hodgkin's disease, nodular sclerosis type, stage III. The patient is alive and relatively well six years after presentation, having been treated with a combination of chemotherapeutic regimens.Previously reported cases of Gaucher's disease concurrent with Hodgkin's disease are reviewed.     

Suppressive therapy of nontoxic goiter

In a double-blind study, 114 patients with clinically benign nontoxic goiter were treated either with liothyronine (T3), 50 μg/day, or thyroxine (T4), 200 μg/day. After 12 weeks of therapy, patients whose goiters decreased in size were continued on the same therapy for an additional 16 weeks. Those who did not respond were randomly divided into two groups: in one group the same dose of the same medication was continued, and in the other twice the dose of their original medication was given. By the end of 28 weeks, 40 of 54 patients treated with T3 and 29 of 59 patients treated with T4 showed a significant decrease in goiter size. The difference in effectiveness of the two agents was statistically significant (p < 0.025). Both T3 and T4 were effective in reducing small goiters, but T4 was relatively ineffective in shrinking large goiters. Duration of treatment, rather than dose of thyroid hormone, was the major determinant of goiter shrinkage.T3 produced a uniform and consistent depression of radioiodine uptake and circulating hormonal iodine levels, and was effective shrinking both small and large thyroid nodules, whether or not radioiodine uptake was reduced to hypothyroid levels. T4 uniformly increased circulating hormonal iodine levels. However, in T4-treated patients who responded with regression of thyroid nodules, suppression of radioiodine uptake was substantially greater than in those who did not respond.     

Interaction of glucocorticoids and androgens with skeletal muscle.

This review is a discussion of recent developments in our understanding of the metabolic changes that occur in skeletal muscle following treatment with glucocorticoid and androgenic steroid hormones. Exposure of muscle to glucocorticoids results in protein wasting due to a reduction in protein synthesis and an increase in intracellular proteolysis. The protease involved in this response appears to be located in the myofibrillar fraction and its activity is increased by glucocorticoid treatment as well as starvation, diabetes, and tumor-induced cachexia. Treatment with androgens causes an anabolic response in skeletal muscle, mainly due to enhancement of protein-synthesizing machinery. These metabolic changes are reviewed in the light of our current knowledge of the functional role of receptor proteins in steroid hormone action. In rat muscle, two classes of receptors are present that bind cortisol and the synthetic steroids dexamethasone and triamcinolone acetonide, respectively. The cortisol-binding macro-molecule resembles cortisol-binding glubulin or transcortin in several of its physicochemical properties. Attempts to identify specific receptors for androgens in rat skeletal muscle have not been successful. However, in this tissue androgens compete, both in vivo and in vitro, with the receptor proteins that bind dexamethasone. Thus the antagonism of glucocorticoid-induced muscle wasting by concomitant androgen administration may be a consequence of the competition between these steroids for the same site on a receptor in muscle which mediates the catabolic action of glucocorticoids. Current progress in the area of muscle response to steroidal hormones depends on the development of procedures for the measurement and identification of proteolytic enzymes in muscles that are involved in the muscle-wasting diseases. A new approach to the study of muscle protein degradation is based on evidence that 3-methylhistidine is a unique amino acid insofar as it is present in skeletal muscle in relatively high concentrations. The methylation of histidine to form this derivative takes place only after histidine is incorporated into protein. Since the methyl derivative is not reutilized for protein synthesis, the rate of release of 3-methylhistidine from muscle serves as a marker for protein degradation. Future studies are also required to assess the role of normal and abnormal concentrations of blood glucocorticoids in muscle metabolism, and to delineate the sequence of events occurring in these target cells following cytoplasmic binding of the hormones and culminating in the catabolic response.     

Extralymphatic Hodgkin's disease: Prognosis and response to therapy

Three hundred eighteen patients with pathologic stage IA and IB, IIA and IIB, and IIIA Hodgkin's disease who entered into Stanford University Medical Center randomized trials comparing radiation therapy alone to radiation therapy plus six cycles of adjuvant chemotherapy were evaluated. Of these, 54 patients had extralymphatic (E) lesions. There were five relapses among these patients (9 percent), not different from the 37 relapses among the remaining 264 patients (14 percent) with Hodgkin's disease confined to the lymphatic system. Actuarial survival and freedom from relapse were not significantly different for patients with or without extralymphatic disease. The survival of patients with extralymphatic disease was similar whether they received radiation therapy alone or radiation therapy plus chemotherapy.     

Cardiac failure in Addison's disease

In an average 30 years of follow-up study, seven of 22 patients with primary adrenal insufficiency have had cardiac failure. Comparison of these seven with the 15 who remain free of this complication revealed that the former group were somewhat older and had higher incidences of unrelated cardiac disease and of nonsteroid-dependent hypertension, but that their replacement regimens, with respect to sodium supplementation and sodium-retaining steroids, were identical with the latter. Coincident with the appearance of cardiac failure, all seven patients had a decrease in sodium requirements. Adequate control of the adrenal disease was subsequently possible with elimination of mineralocorticoid support in one of the six who had initially required this therapy and a reduction in dosage in the other five. In all seven, dietary sodium supplements were no longer required. In three patients with severe failure, sodium restriction was imposed and diuretics were added, although the latter therapy has required close monitoring to avoid sodium depletion.     

Acquired Gaucher's cells in Hodgkin's disease

A patient with Hodgkin's disease associated with low glucocerebrosidase levels in the peripheral leukocytes, and Gaucher's cells in the bone marrow and lymph nodes, is described. After MOPP therapy, complete remission of Hodgkin's disease was accompanied by normalization of the glucocerebrosidase level and disappearance of Gaucher's cells. This observation appears unique when compared with the four cases of combined Hodgkin's and Gaucher's disease reported in earlier literature in which Gaucher's disease remained unchanged after chemotherapy. We conclude that our patient had Hodgkin's disease and acquired Gaucher's cells with diminished glucocerebrosidase levels, rather than a combination of Hodgkin's disease and Gaucher's disease.     

Sporothrix schenckii meningitis in a farmer with Hodgkin's disease

A fatal case of chronic meningeal sporotrichosis occurring as an opportunistic infection in a patient with Hodgkin's disease is presented. A pulmonary source of infection was identified at autopsy. The diagnostic importance of the isolation of Sporothrix schenckii from cerebrospinal fluid, even if only from a single specimen, is stressed.     

Circulating immune complexes in Hodgkin's disease

Levels of circulating immune complexes (CIC) in the serum of patients with Hodgkin's disease were measured by the Raji cell radioimmunoassay. Elevated levels of immune complexes (mean value of 49 μg/ml ± 21 SE) were detected in 20 of 40 (50 per cent) untreated patients. After treatment, the level of CIC was normal (< 15 μg/ml) in 39 of 41 patients. Recurrent disease developed in two of the 39 patients with normal post-treatment levels of CIC and in one of the two patients with elevated post-treatment levels during the follow-up period of six months to six years. Elevated levels of CIC were detected in patients with Hodgkin's disease in stages I, II and III but not in stage IV. No significant correlations were found in the frequency of elevated levels of CIC or the values observed, and the presence or absence of symptoms (fever, sweats, weight loss) or the histologic subtype of the tumor. Our data indicate that the measurement of CIC by the sensitive and specific Raji cell assay may prove useful in the management of patients with Hodgkin's disease. In particular, serial measurement of the level of CIC could be employed to monitor the response to treatment and to detect recurrent diseases.     

Immune thrombocytopenia and Gaucher's disease

A 35-year-old Ashkenazi woman with Gaucher's disease was evaluated for persistent thrombocytopenia. The diagnosis of Gaucher's disease was made by bone marrow aspiration and confirmed by the determination of glucocerebrosidase levels in leukocytes and cultured skin fibroblasts. Studies of platelet-associated IgG and in vivo platelet survival demonstrated immune-mediated destruction of platelets consistent with immune thrombocytopenic purpura. A trial of prednisone had no effect on the platelet count. Total splenectomy resulted in a complete and prolonged remission. The clinical implications of Gaucher's disease and concurrent immune thrombocytopenic purpura are discussed.