Anthony V. Pisciotta

Increased Incidence of Acute Leukemia in Polycythemia Vera Associated with Chlorambucil Therapy

In studies to determine the optimal treatment for polycythemia vera, 431 previously untreated patients whose disease met established diagnostic criteria were entered into a prospective, randomized controlled trial between 1967 and 1974. Three treatment regimens were used: phlebotomy alone, chlorambucil supplemented by phlebotomy, or radioactive phosphorus supplemented by phlebotomy. Despite minor differences in age and sex, the three groups were comparable in initial hematocrit, white-cell and platelet counts, and disease-related symptoms. The median duration of follow-up is now more than 6 1/2 years. As of February 15, 1980, there were no statistically significant differences in survival among the groups. However, the risk of acute leukemia in patients given chlorambucil was 2.3 times that in patients given radioactive phosphorus and 13 times that in patients treated with phlebotomy alone. The increased incidence of leukemia during chlorambucil treatment is statistically significant (P less than or equal to 0.002); accordingly, the Polycythemia Vera Study Group has discontinued the use of chlorambucil in the treatment of polycythemia vera.

Anemia, Cataracts, and Seizures in Patient With Glucose-6-Phosphate Dehydrogenase Deficiency

CONGENITAL CONGENITAL nonspherocytic hemolytic anemia is a heterogenous group of hemolytic disorders characterized by disturbances of glycolytic metabolism in the erythrocyte. One category has been associated with defects in the Embden-Meyerhof pathway of glucose metabolism; patients with erythrocytes defective in pyruvate kinase 1 and triose phosphate isomerase 2 activity have been described. Another group has been associated with diminished glucose-6-phosphate dehydrogenase (G-6-PD) activity. This abnormality results in an inability to generate reduced triphosphopyridine nucleotide (TPNH) in the hexose monophosphate shunt. Deficient erythrocyte G-6-PD activity is associated with a number of hemolytic diseases of variable severity. In some cases, red cells deficient in this enzyme activity do not ordinarily hemolyze unless the patient is exposed to certain oxidizing drugs, such as primaquine. 3 This manifestation occurs in 10% to 15% of American Negro men as a sex-linked recessive trait. On the other hand, most affected Caucasians show almost constant hemolysis. Because

Fibrinolytic purpura in acute leukemia

Summary 1.In an eighty-two year old man, acute leukemia was associated with fatal hemorrhagic phenomena. The chief factor in the mechanism of hemorrhage was destruction of the fibrin clot by a fibrinolytic enzyme. 2.The patient also showed thrombocytopenia due to absence of megakaryocytes, increase in prothrombin time, impairment of prothrombin consumption and increase of a heparinoid substance with antithrombic activity.

On the Possible Mechanisms and Predictability of Clozapine-Induced Agranulocytosis

SummaryStudies were conducted on serum removed from 15 patients before, during, and after, clozapine-induced agranulocytosis. Cytotoxic studies were compared with samples taken from patients during treatment with clozapine who did not develop agranulocytosis or treatment controls (TC); additional controls consisted of allogeneic (NC) and autogeneic serum from apparently normal people. The effect of serum on measurable functions of polymorphonuclear neutrophils (PMNs) taken from normal people was tested. Procedures under study included suppression of post-phagocytosis-induced 14CO2-indicated respiratory burst, as well as ejection of trypan blue by test PMNs. PMNs exposed to active agranulocytosis serum plus complement displayed diminished 14CO2 emission during phagocytosis or failed to eject trypan blue. PMNs exposed to serum of TC and NC continued to function normally as regards 14CO2 emission and trypan blue ejection. Five patients studied before the development of agranulocytosis showed suppressed PMN function, which increased to peak value during agranulocytosis and then disappeared within 40 days of recovery. Similar suppression of colony forming units of granulocytes and macrophages (CFU-GM) was found whenever agranulocytosis serum was included in the marrow culture. The cytotoxic material required complement for its full expression, was not dialysable, was neutralised by anti-IgM serum, and was absorbed by test PMNs. Furthermore, solutions of clozapine or 5 of its metabolites offered no similar suppression of PMN function in vitro after incubation in an aqueous medium or with normal serum. These observations favour development of an immunogenic clone in sensitive people during active treatment with clozapine, which eventually leads to precipitous depletion of PMNs and their precursors. The early appearance of this suppressive substance may offer an early warning for development of agranulocytosis.

Chronic granulocytic leukemia following radiation therapy for Hodgkin's disease

A 33‐year‐old white man was treated with irradiation for Hodgkins disease involving the mediastinum; four years later he developed typical Philadelphia chromosome‐positive chronic granulocytic leukemia. The patient has been treated with chronic low‐dose busulfan to maintain peripheral blood counts in the normal range and he continues to remain well 27 years after the initial diagnosis of Hodgkins disease and 23 years following the onset of leukemia.

Hodgkin's disease with leptomeningeal involvement: Report of a case with long survival

A 30‐year‐old white man with Stage IV B Hodgkins disease, mixed cellularity type, developed leptomeningeal involvement shortly after relapsing on nitrogen mustard, Oncovin (vincristine), procarbazine, and prednisone (MOPP), and while receiving Adriamycin (doxorubicin), bleomycin, Velban (vinblastine), and dacarbazine (ABVD). Whole brain irradiation and intrathecal methotrexate were successfully incorporated into his treatment program. The patient has now been in complete remission for more than 40 months. A review of this rare complication of Hodgkins disease is presented.

Thermodynamics of equilibria of hemoglobins M Milwaukee-I and Saskatoon and isolated chains of hemoglobin a with carbon monoxide

Abstract The thermodynamic parameters of the CO-equilibria of isolated chains of hemoglobin A and of two α-chains in hemoglobins M Milwaukee-I and Saskatoon at 25°, pH 7.0 were determined. The parameters for the binding of the first CO molecule to the hemoglobins M were ΔH′=−17 and −18 kcal/mole heme and ΔS′=−30 and −29 e.u. for hemoglobins M Milwaukee-I and Saskatoon, respectively. In contrast to this the characteristics of the second step of the binding were ΔH′=+5.9 · and +4.3 kcal/mole and ΔS′=+51 and +49 e.u. These values for the second step were also significantly different from those of the isolated α-chain (ΔH′=−15 kcal/mole and ΔS′=−11 e.u.).