Acute Granulocytic Leukemia Research Articles

Serum myeloperoxidase in leukaemia and polycythaemia vera.

Myeloperoxidase is a haem enzyme which is a characteristic constituent of the neutrophil granulocyte series and of monocytes.Using myeloperoxidase purified from human granulocytes and myelocytes, a radio‐immunodiffusion method for the measurement of this protein has been developed. Normal sera were found to contain only traces (up to 2 mg/l) of myeloperoxidase. Elevated concentrations (up to above 10 mg/l) were found in some patients with acute leukaemia, monocytic leukaemia, and chronic myelocytic leukaemia. Minor elevations occurred in 5 of 13 cases of polycythaemia vera.The findings are discussed in relation to current knowledge on the synthesis and intracellular localization of myeloperoxidase.

Degeneration of the pineal gland of patients with cancer.

Gross and microscopic changes of the pineal gland in 275 cancer patients were studied. Multiple slit-like cystic cavities, gliosis, and large numbers of Rosenthal fibers were found in the enlarged pineal gland of 31 patients (mostly children and adolescents). Twenty-four of the 31 patients died with acute granulocytic or lymphocytic leukemia. These morphological abnormalities of the pineal gland have been recognized for a long time. However, a review of the literature revealed no previous description of such changes in the pineal gland of cancer patients.

Serine and Aspartic Acid Metabolism in Leukemic Leukocytes: Correlation to Effectiveness of Therapy

Abstract Leukocytes from patients with acute granulocytic leukemia (AGL), acute monocytic leukemia (AMoL) and blastic crisis of chronic granulocytic leukemia (BC) were incubated with serine-U-C14 or aspartic acid-U-C14. The metabolism was followed by determination of radioactivity of CO2, lipids, proteins, organic acids, and nucleotides. Leukemic leukocytes in AGL, AMoL, and BC exhibit high serine utilization compared to lymphocytic leukemias. Significant changes in the metabolic pattern of the leukocytes from patients with chronic granulocytic leukemia (CGL) preceded the onset of blastic crisis. Serine utilization remained abnormal in two patients with AGL after complete remission was achieved. Low conversion of serine to CO2 in AMoL was associated with achievement of complete remission and long survival time. Aspartic acid was most actively metabolized by leukemic cells in BC. The results of these studies indicate that the metabolic pattern of serine and aspartic acid varies with the type of leukemic cell. There is evidence that mature polymorphonuclear (PMN) leukocytes in the blood of leukemic patients may possess an abnormal metabolism.

Colony Growth of Human Leukemic Peripheral Blood Cells In Vitro

Abstract The colony-forming potential of peripheral white blood cells from patients with acute leukemia on normal human peripheral WBC feeder layers has been studied. White blood cells from 12 of 20 patients with acute granulocytic leukemia gave rise to large numbers of colonies, while WBC from eight patients with AGL, four patients with acute lymphocytic leukemia and three patients with acute stem cell leukemia gave rise to no colonies or only small numbers. Colonies formed from WBC of patients with AGL appear to go through a process of morphologic maturation to segmented granulocyte forms. Leukemic WBC will not serve as feeder layers in this system, but are not inhibitory in this respect. The significance of these findings is discussed.

Colony-stimulating Factor and Inhibitor Levels in Acute Granulocytic Leukemia

Abstract Assays were performed on bone marrow colony-stimulating-factor (CSF) levels in the serum and urine of 33 patients with acute granulocytic and myelomonocytic leukemia. Of 251 serum samples, 30% showed elevated CSF levels as did 53% of 1422 urines tested. Levels of serum inhibitors of colony formation were abnormally low or undetectable in 57% of sera from leukemic patients. Patients in relapse were unable to respond to infections by developing high serum CSF levels and low serum-inhibitor levels were more common in patients with a short survival time and in some types of patient during relapses.

Cytosine arabinoside in acute granulocytic leukemia.

Gytosine arabinoside (Ara‐G) is an antimetabolite of demonstrated activity in acute granulocytic leukemia (AGL). Between 1966 and 1969, 49 patients with AGL received remission induction chemotherapy with this drug at the National Gancer Institute. Ara‐G was given by 4 hour infusion at a dose of 70 to 150 mg. per square meter per day in repeated 4 day courses. Gomplete remissions were achieved in 42 per cent of patients. Of patients receiving Ara‐G as initial chemotherapy, 25 per cent died during attempted induction and 25 per cent attained complete remission; of patients who had received prior chemotherapy (irrespective of response), 67 per cent achieved complete remission (p<0.02). Infection (73 per cent} and hepatic dysfunction (44 per cent) were common complications of therapy. Median duration of remission in 21 patients receiving weekly Ara‐G at 75 mg. per square meter subcutaneously as maintenance chemotherapy was 5 months. Median survival in patients achieving remission with Ara‐G was 17 months; patients failing induction with this drug lived a median of 6 months. Ara‐G is an effective and well‐tolerated chemotherapeutic agent in AGL.

Myelomonocytic leukemia: disorderly proliferation of all marrow cells.

Myelomonocytic leukemia, our preferred designation for leukemia involving two or more marrow cell lines, is currently the most common type of leukemia seen at the Mayo Clinic. In an attempt to clarify the clinical picture and natural course of this myeloproliferative disorder, 132 patients first seen between 1955 and 1959 were studied. The disease, which usually had its onset after 50 years of age, was preceded in 41 patients by a preleukemic phase of variable duration. At the onset of overt leukemia, predominant involvement was of the erythrocytic and megakaryocytic compartments; during this phase the hematologic findings often suggested vitamin B12 or folate deficiency. As the disease evolved, it resembled acute granulocytic or monocytic leukemia or a mixture of these. The course, which was variable and unpredictable, ranged from a few weeks to several years.

Smoldering acute leukemia. Clinical and cytogenetic studies in six patients.

Smoldering acute leukemia is a variant of acute granulocytic leukemia which may have a more benign course than the usual form of acute leukemia. The bone marrow shows increased numbers of blast cells and the blood shows cytopenias without blast cells. Such patients do not have life-threatening acute infection or bleeding seen in patients with acute leukemia. The absence of these findings help to distinguish smoldering acute leukemia from aleukemic

Smoldering Acute Leukemia

Smoldering acute leukemia is a variant of acute granulocytic leukemia which may have a more benign course than the usual form of acute leukemia. The bone marrow shows increased numbers of blast cells and the blood shows cytopenias without blast cells. Such patients do not have life-threatening acute infection or bleeding seen in patients with acute leukemia. The absence of these findings help to distinguish smoldering acute leukemia from aleukemic

Acid phosphatase isoenzyme in human leukocytes in normal and pathologic conditions.

Acid phosphatase in human leukocytes was examined in a large number of patients with a variety of hematologic diseases. In chronic lymphocytic leukemia the total leukocyte acid phosphatase activity was markedly decreased. This was due to the drastic increase of enzyme-poor leukemic lymphocytes and the concomitant decrease of enzyme-rich monocytes and neutrophils. Further examination by disc gel electrophoresis revealed that the leukocytes in this disease contained only one of the five acid phosphatase isoenzymes present in a normal leukocyte preparation. Total acid phosphatase activity was not significantly altered in other hematologic disorders, yet different ratios of the isoenzymes shown by disc gel electrophoresis were observed in Hodgkin's disease, chronic granulocytic leukemia, acute granulocytic leukemia, infectious mononucleosis and leukemic reticuloendotheliosis.

Leukopoietic activity in human urine. The granulocytic leukemias.

Abstract Urine from normal persons and patients with acute and chronic leukemia was tested for ability to stimulate granulocyte bone-marrow colony growth in vitro. All eight patients with chronic granulocytic leukemia had high levels of colonygrowth-stimulating activity. Six out of seven patients with acute stem-cell or acute lymphatic leukemia also had high levels, whereas nine out of 15 patients with untreated acute granulocytic leukemia had low or absent levels. In acute granulocytic leukemia, levels may rise during treatment, often becoming normal to very high with remission, only to fall again to subnormal levels with relapse.

Acute granulocytic leukemia complicating Hodgkin's disease

Acute granulocytic leukemia complicating Hodgkin's disease

Acute Granulocytic Leukemia Complicating Hodgkin's Disease

The coexistence of acute leukemia and Hodgkin's disease is rare. 1 However, Crosby 2 in a recent survey estimated the incidence of acute granulocytic leukemia in Hodgkin's disease to be increased tenfold, and suggested that this may be a sequel to radiotherapy, not directly related to the disease. We present here two patients with Hodgkin's disease of long duration, in both of whom acute leukemia developed. A refractory sideroblastic anemia, which rapidly progressed to erythroleukemia (acute Di Guglielmo syndrome) developed in one; pancytopenia developed in the other, who died of acute granulocytic leukemia nine months later. Patient Summaries In 1954, a 36-year-old woman had Hodgkin's disease involving cervical, supraclavicular, and mediastinal nodes. She received radiotherapy (2,400 roentgens) to these areas. Laboratory values were as follows: hemoglobin, 12.4 gm/ 100 ml; leukocytes, 9,100/cu mm, with 58% neutrophils, 21% lymphocytes, 16% monocytes, and 5% eosinophils. In 1960, adenopathy recurred, with systemic symptoms.

Spontaneous rupture of the spleen in acute granulocytic leukaemia

Spontaneous rupture of the spleen in acute leukaemia is of extreme rarity. Although the present case was under close observation in hospital, rupture of the spleen presented considerable diagnostic difficulty. The patient, a man of 53yr., with untreated acute granulocytic leukaemia without obvious splenic enlargement was awakened from sleep by severe epigastric pain. At laparotomy 48hr. later, a grossly disrupted and fragmented spleen weighing 240g. was removed. The patient died four days after splenectomy from unexpected cardiac arrest. Histological examination showed subcapsular haemorrhages in a leukaemic spleen.

Megaloblastic anemia of pregnancy simulating acute leukemia.

Two patients had megaloblastic anemia of pregnancy, presenting with histories and bone marrow smears compatible with acute granulocytic leukemia. A review of the reported cases of acute leukemia in pregnancy indicates the difficulty in making a definitive diagnosis on the basis of clinical history and smears of the blood and bone marrow. The role of concurrent iron deficiency in obscuring the diagnosis of megaloblastic anemia is suggested. A brief trial of folic acid and vitamin B12 is indicated in all patients with equivocal marrow findings or the possibility of vitamin deficiency.

To Treat or Not to Treat Acute Granulocytic Leukemia. II

In a recent editorial in this journal¹Crosby expressed the opinion that there are certain varieties of acute myeloblastic leukemia (AML) in which specific antileukemic therapy should not be employed. Specifically, he stated that the following types of patients are "not improved by chemotherapy": those with such morphologic subvarieties of this disease as myelomonocytic, promyelocytic, and acute granulocytic leukemia with megaloblastosis (erythroblastic leukemia); patients with the smouldering type of acute leukemia, and patients over the age of 50. In a previous study,²we were unable to demonstrate any influence of cell type or age upon the rate of response of AML to mercaptopurine. However, the number of patients treated with mercaptopurine in that series was small (63 patients) and experience with certain of the less common varieties of the disease was limited. We therefore have reviewed patients treated in our clinics since that date in order to enlarge

Myeloid Metaplasia: A Study of 98 Cases

A comparative study of 98 cases of myeloid metaplasia and 93 cases of chronic granulocytic leukemia suggests a common pathogenetic mechanism. The laboratory procedures most helpful in differentiation were leukocyte alkaline phosphatase determinations and cytogenetic studies. Acute leukemia occurring in four cases of myeloid metaplasia supports the theory that polycythemia vera, myeloid metaplasia, and chronic and acute granulocytic leukemia constitute a spectrum of myeloproliferative disorders.

Cytogenetic Findings in Erythroleukemia

Abstract Cytogenetic studies of marrow cell lines were done in 10 cases of erythroleukemia and in 6 cases of potentially preleukemic refractory megaloblastic anemia. Abnormalities consisting of aneuploidy, increased polyploidy and chromosome breakage were found in 9 cases, 6 in the erythroleukemia group and 3 in the refractory anemia group. Observations in these cases support the concept that erythroleukemia is a clinical variant of acute granulocytic leukemia. They also indicate that marrow chromosome analysis can assist in the diagnosis of cases where leukemia is suspected but not clinically proven.

Treatment of AGL

<h3>To the Editor.</h3> —The editorial by William H. Crosby, MD, "To Treat or Not to Treat Acute Granulocytic Leukemia" (Arch Intern Med<b>122</b>: 79-80 [July] 1968), prompts the following comments. The decision whether or not to treat intensively a given patient with acute granulocytic leukemia (AGL) is indeed a difficult one. In his editorial, Dr. Crosby attempts to resolve the problem by listing a series of six variants of AGL in which "the remission rate is zero," and in which, therefore, treatment other than general support is not indicated. Our experience does not accord with Dr. Crosby's dicta. Over the past six years we have personally observed 169 patients with AGL who have been treated within two weeks (usually within a few days) of the time of diagnosis. These patients have all been treated on studies of the Acute Leukemia Cooperative Chemotherapy Group B (ALB) with one or several of

Treatment of AGL.

Editor. —The editorial by William H. Crosby, MD, To Treat or Not to Treat Acute Granulocytic (Arch Intern Med 122 : 79-80 [July] 1968), prompts following comments. The decision whether or not to treat intensively a given patient with acute granulocytic leukemia (AGL) is indeed a difficult one. In his editorial, Dr. Crosby attempts to resolve problem by listing a series of six variants of AGL in which the remission rate is zero, and in which, therefore, treatment other than general support is not indicated. Our experience does not accord with Dr. Crosby's dicta. Over past six years we have personally observed 169 patients with AGL who have been treated within two weeks (usually within a few days) of time of diagnosis. These patients have all been treated on studies of Acute Leukemia Cooperative Chemotherapy Group B (ALB) with one or several of