Pure red cell aplasia associated with angioimmunoblastic lymphadenopathy with dysproteinemia.

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) can best be described as a disorder of T-cells resulting in amplification of the B-cell response and clinical symptoms of lymphadenopathy, fever, hepatosplenomegaly, and a variety of blood abnormalities. Pure red cell aplasia (PRCA), an autoimmune disorder resulting in selective aplasia of the erythroid series, has only rarely been associated with AILD. Herein we report three cases of AILD and PRCA. Serum from one patient was available for study and contained a dose-dependent inhibitor of the CFU-E but not CFU-GM cultures from normal bone marrow. This activity was found in the globulin fraction after ammonium sulfate precipitation. Patients with AILD are known to make antibodies to many autologous epitopes, and the most well-characterized mechanism of PRCA involves antibodies to red cell precursors. Our serum data are consistent with the hypothesis that such an antibody existed in our patient. Aggressive treatment of these patients resulted in transient improvement in two; however, all three died without achieving a durable complete remission with two dying of infectious complications.

In vivo regulation of human leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase: increased enzyme protein concentration and catalytic efficiency in human leukemia and lymphoma.

The activity of microsomal HMG-CoA reductase in freshly isolated leukocytes from patients with a variety of hematologic malignancies was significantly increased (up to 20-fold) when compared to enzyme activity in leukocytes from normal subjects (average 10.3 +/- 0.8 pmol/min per mg). Increased enzyme activity was not due to nonspecific leukocyte stimulation or to the presence of a malignancy, since normal enzyme activity was observed in subjects with either viral illnesses or solid tumors. Increased HMG-CoA reductase activity accompanying hematologic malignancy could also not be attributed to alterations in enzyme-substrate kinetic parameters (Km), or to alterations in the phosphorylation state or thiol-disulfide status of the enzyme, nor was it correlated with differences in serum lipid or lipoprotein concentrations. The increase (3.6-fold) in HMG-CoA reductase activity in leukocytes from patients with preleukemia was due entirely to a rise in enzyme catalytic efficiency (specific activity), whereas the increase (4.3-fold) observed in leukocytes from patients with overt leukemia or non-Hodgkin's lymphoma was due to a concomitant increase in both enzyme catalytic efficiency (2.5-fold) and enzyme protein concentration (1.6-fold). Similar increases in HMG-CoA reductase activity and catalytic efficiency were also noted for both transformed, nonmalignant, and malignant cultured leukocytes, suggesting that increased enzyme catalytic efficiency is not a nonspecific consequence of physiological changes occurring in response to the malignancy but may be an integral aspect of the malignant phenotype. HMG-CoA reductase protein concentrations, however, were not elevated in either transformed, nonmalignant, or malignant cultured leukocytes, suggesting that increases in enzyme protein levels may be secondary to other physiological changes that occur during the development of overt leukemia. Taken together, these observations suggest that an increase in the activity of HMG-CoA reductase, the rate-controlling enzyme in cholesterol synthesis, is a common occurrence in human hematologic malignancies and that a biphasic elevation of enzyme activity may exist in malignant leukocytes, such that changes in catalytic activity may occur early in tumorigenesis and may be followed by secondary changes in enzyme levels.

Myelodysplastic syndromes presenting in pregnancy. A report of five cases and the clinical outcome.

Five female patients, ranging in age between 22 and 36 years, presented with myelodysplastic syndromes during pregnancy between June 1982 and March 1987. Three of these five cases evolved into acute leukemia. A bone marrow transplant was attempted in the fourth. It is suggested that the association of myelodysplastic syndromes during pregnancy is more than coincidental and that acute leukemia evolves in a majority of these cases. Furthermore, refractory macrocytic anemias in pregnancy need to be carefully evaluated for a primary myelodysplastic state.

Total body irradiation for stage II-IV non-Hodgkin's lymphoma: ten-year follow-up.

Between 1972 and 1977, a prospective study was conducted at the University of Florida on the role of total body irradiation (TBI) in the management of stage II-IV non-Hodgkin's lymphoma (NHL). Forty-four consecutive de novo (DN) patients (including ten stage II, 18 stage III, and 16 stage IV), as well as 16 previously treated (PT) patients, were accrued. Twenty of the 44 DN patients were symptomatic at presentation. Complete clinical responses were obtained in 20 of the 27 DN patients with favorable histologies (FH), and six of the 17 with unfavorable histologies (UH). Partial responses were obtained in six patients with FH and 11 patients with UH; only one patient showed no response to TBI. By univariate analysis, PT patients showed a trend for decreased relapse-free survival (P = .066) and decreased survival (P = .093). Multivariate analysis identified the best predictors of response rate to be histology (P = .0146) and marrow involvement (P = .0854); of relapse-free survival, histology (P = .0035), and TBI dose (P = .002); and of absolute survival, age (P = .0012), histology (P = .012), and TBI dose (P = .029). Thirty of the 41 patients who relapsed underwent salvage treatment with either chemotherapy or radiation. Twenty-three of the 30 undergoing salvage therapy obtained a second complete clinical response. There were no treatment-related deaths. The most common complication was thrombocytopenia. The major late complications were myeloproliferative disorders in four patients, which occurred only after cumulative TBI doses in excess of 200 cGy.

Intensive short-term chemotherapy for patients with acute myelogenous leukemia: long-term follow-up.

Our pilot study addresses the problem of early relapse from complete remission in young adults with acute myelogenous leukemia (AML). Twelve patients with AML, 16-58 years of age, were entered in a study of four intense courses of cytotoxic chemotherapy using the following drugs: cytarabine, daunorubicin, 5-azacitidine, and 6-thioguanine. They received no maintenance therapy. Nine of 12 patients achieved complete response. With a minimum follow-up of 35 months, the observed disease-free survival at 2 years was 67% (14 +/- SE) and the actuarial disease-free survival at 4 years was 38% (17 +/- SE). It appears that brief intensive chemotherapy early in the management of AML can produce prolonged remission without the need for maintenance therapy.

Intravenous immunoglobulin administration in the treatment of severe chronic immune thrombocytopenic purpura.

Human immunoglobulin was administered intravenously to nine adult patients having severe chronic immune thrombocytopenia purpura. The response in three patients was an increase in the platelet count to greater than 50,000/mm3, a hemostatically adequate level. Response was associated with a pretreatment platelet-associated immunoglobulin level of more than 5,000 molecules per platelet, and successful treatment resulted in a decrease in that level. In those patients with pretreatment platelet-associated immunoglobulin levels less than 5,000 molecules per platelet, there was neither a significant decrease in that level nor an increase in their platelet count. Immunoglobulin infusion may prove useful for selected patients with severe chronic immune thrombocytopenia.

High-dose intravenous immunoglobulin therapy in patients with immune thrombocytopenic purpura.

Four patients with severe chronic immune thrombocytopenic purpura who were refractory to all conventional therapy for that disorder were initially seen with either refractory bleeding or the necessity for an operation. We treated each of these patients with intravenous human serum immunoglobulin, and three of the four patients had a rapid and substantial increase in their platelet counts. This new method for ameliorating chronic immune thrombocytopenic purpura deserves further study and consideration.

Iron studies in hemophilia.

Although iron deficiency is not recognized as a usual complication of hemophilia, we questioned whether intermittent occult loss of blood in urine or stool might predispose hemophiliacs to chronic iron deficiency. Seven men with factor VII and one with factor IX deficiency were studied. Blood studied, bone marrow aspirates, urine and stool samples, and ferrokinetics with total-body counting up to five months were examined. These data showed no excessive loss of blood during the study period; however, marrow iron stores were decidedly decreased, being absent in four subjects. We suggest that in some hemophiliacs, iron deposits in tissues such as synovial membranes may form a high proportion of the body's total iron stores.

Cutaneous melanoma and its relation to melanoma of the uveal tract.

Current tactics under study in the control of cutaneous melanoma may prove to be of benefit in management of uveal melanoma. These include precise staging at diagnosis and analysis of pathologic data correlated with the subsequent clinical course. The potential role of adjuvant chemotherapy and immunotherapy is discussed.

Pyridoxine-responsive hypolipidemia and hypocholesterolemia in a patient with pyridoxine-responsive anemia.

A case of pyridoxine-responsive anemia with hypolipidemia and hypocholesterolemia responsive to pyridoxine is presented. It is suggested that abnormalities of the serum lipids are common but often unrecognized in patients with pyridoxine-responsive anemia. A mechanism to explain their occurrence is postulated.