Untreated Leukemia Research Articles

Nitrous oxide reduces growth of experimental rat leukemia

The ability of nitrous oxide to inhibit the in vivo growth of hematological neoplasms was investigated in a rat model for acute myeloid leukemia (BNML). Nitrous oxide, administered in a concentration of 67% with 33% oxygen, resulted in a reduction of spleen and liver weights of approx. 30%, as compared with leukemic rats kept in ambient air. Peripheral white cell counts were also considerably lower in the treated rats. Plasma levels of vitamin B 12 were found to be elevated in untreated leukemia, but fell to about normal levels after nitrous oxide exposure. On the contrary, folic acid levels were low in untreated leukemic rats, and significantly higher in animals exposed to nitrous oxide. The observed effects of nitrous oxide appeared to be dose-dependent. The deoxyuridine suppression test performed with leukemic cells became abnormal after nitrous oxide inhalation, in accordance with the effect on normal bone marrow. These results indicate that the interference of nitrous oxide with vitamin B 12-related metabolism, which leads to impairment of de novo thymidine synthesis, has the potency to reduce leukemic proliferation in vivo.

Acute lymphoblastic leukaemia associated antigen. III Alterations in expression during treatment and in relapse

315 adult patients with untreated leukaemia or lymphoma attending St. Bartholomew's Hospital, London, between June 1973 and December 1978 were studied. Forty-five had blast cells which were specifically reactive with antibody to common (non-T, non-B) ALL ( = cALL +). The morphological diagnosis was of ALL (33 cases), AUL (5 cases) or Ph 1 positive CML in blast crisis (4 cases). Four of the ALL cases were Ph 1 positive and had had no clinically evident CML phase. Bone marrow suspensions from 19 of these patients have been examined serially for up to 4 years in order to assess the stability of the immunological phenotype and the possible prognostic value of monitoring levels of ALL + cells throughout treatment. In some instances the re-appearance of cALL + cells preceded relapse. Isolated relapses of the CNS, skin or testis were also associated with transient increases in cALL + cells in the bone marrow. The potential monitoring value of anti-ALL was compromised by three observations: the rapid appearance of leukaemic blasts in relapse with no prior detectable increase in cALL + cells, the re-appearance of weakly stained cALL + cells without subsequent relapse particularly during post maintenance chemotherapy associated lymphocytosis and finally the emergence of cALL antigen negative leukaemic cells in relapse. Of 119 other ALL cases studied (mostly children) 20 showed a phenotypic shift of membrane marker expression in relapse. The clinical and biological implications of these observations are discussed.

Nucleotide composition analysis of tRNA from leukemia patient cell samples and human cell lines.

A technique developed for analysis of less than microgram quantities of tRNA has been applied to the study of human leukemia. Leucocytes from peripheal blood and bone marrow samples of six, untreated leukemia patients and cells of five different established human cell lines were maintained for 18 hours in media containing (32P)-phosphate. Incorporation of radioactive phosphate into the cells from the patient samples was slightly less than that of the cell lines. Likewise, incorporation of (32P)-phosphate into the tRNA of the patient samples (approximately 5 x 106 DPM/mug tRNA) was also less then that incorporated into the tRNA of the cell lines. The major and minor nucleotide compositions of the unfractionated tRNA preparations from each patient sample and each cell line were determined and compared. Similarities and differences in the major and minor nucleotide compositions of the tRNA preparations are discussed with reference to types of leukemia and the importance of patient sample analysis versus analysis of cultured human cells.

Cytologic expressions of spontaneous tumor-specific immunity in an untreated myelomonocytic leukemia. Sustained, complete remission following minimal immunosuppressive therapy.

A monocytosis of about 40% had been persistently described for several months in a 49-year-old Caucasian female during examination for benign upper respiratory and gastrointestinal viral-type infections. Finally, a persistent low-grade fever, asthenia and abdominal discomfort led to the hematological diagnosis of acute myelomonocytic leukemia. The past history revealed multiple atopies. In the peripheral blood there were different kinds of lymphocytes with predominance of small, round agranular ones and moderate eosinophilia; the leukemic cells were large monocytoid elements with bizarre poly-lobulated nuclei of fine chromatin mesh, pale blue, agranular cytoplasm with many large vacuoles. The remarkable feature was that the monocytoid elements were in spherical clusters of 5–50 or more cells and that these clusters always contained a few small lymphocytes. These clusters were not broken by the smearing on the slide and because of their mass they rolled to the edges of the smear. The length of the smoldering, asymptomatic disease with ‘monocytosis’, the abundance of small lymphocytes and the clustering or rosetting of monocytoid-lymphocytic elements were taken as indications of autoimmune leukemic cytolysis which entertained a partial spontaneous remission or at least a prolonged host-tumor symbiosis. In recognition of these expressions of host-resistance a minimal immunosuppressive therapy (MIST) program was tried. A complete, sustained (40 weeks) remission was obtained since.

Fever in treated and untreated leukemias and hematosarcomas

SummaryThe authors have studied the causes of prolongated fevers during the evolution of malignant hemopathies.Details are given of infectious complications, bacterial or viral, observed during investigations carried out on 208 patients treated at the University Clinic of Louvain.The collected data from the necropsies of 32 patients, died from leukaemia, revealed the high incidence of fungal infections as a cause of prolonged fever.

Chromosomal Aberrations in Irradiated Blood and Blood Cultures of Normal Subjects and of Selected Patients with Chromosomal Abnormality

While performing chromosome studies on the families of patients with congenital malformations and other disorders, we encountered several subjects with an excessive rate of persistent chromosomeor chromatid-type aberrations. Certain of these abnormalities are known to occur in people exposed to ionizing radiation (1, 2), after infection with viruses (3, 4), and in leukemia. In blood cultures from untreated leukemia, an excess of chromosome breaks is uncommon, but the presence of aneuploidy and polyploidy is quite frequent (5, 6). One of our subjects with spontaneous chromosomal aberration had been exposed to excessive X-radiation, but in others no obvious etiological factor could be detected. Persistence of abnormality in the repeated chromosome studies during the period ranging from 12 to 24 months makes viral infection an unlikely cause (3); also, there was no evidence of leukemia on examination of blood and bone marrow. Further follow-up of these subjects is planned, but in the meantime we have irradiated their blood and blood cultures and then processed for chromosome spreads. This was done with the view of finding out whether the rates of chromosomeor chromatid-type aberrations after irradiation in vitro are different in patients with chromosomal abnormalities from rates in normal people.

Leukocyte alkaline phosphatase: electrophoretic variants associated with chronic myelogenous leukemia.

Starch-gel electrophoresis of leukocyte alkaline phosphatases, rendered soluble by treating normal leukocytes with butanol, revealed three electrophoretic variants of the enzyme. The phosphatases in similarly prepared extracts of leukemia cells differed from the normal isozymes in electrophoretic. mobility. A single variant was detected in one case of untreated leukemia; a similar component and three additional ones were seen in leukemia treated with 6-mercaptopurine.

EFFECT OF ADMINISTRATION OF ALKYLATING AGENTS OR 6-MERCAPTOPURINE ON SERUM LEVEL OF DEOXYRIBONUCLEASE I IN LEUKEMIA PATIENTS.

SummarySerum deoxyribonuclease I (DNase I) is slightly lowered in untreated carcinoma patients in comparison with normal subjects. However, there are no significant differences between the serum DNase I of untreated leukemia patients and normal subjects. A reduction in number of leukocytes following therapy with 6-mercaptopurine, nitrogen mustard or Myleran in leukemia patients is accompanied by a lowering in serum DNase I activity. A possible mechanism for the lowering of DNase I activity is discussed.

Insufficiency of acute response of basophil and eosinophil leukocytes and of blood histamine after the administration of ACTH and cortisone in untreated myelocytic leukaemia.

Insufficiency of acute response of basophil and eosinophil leukocytes and of blood histamine after the administration of ACTH and cortisone in untreated myelocytic leukaemia.