thioguanine-anhydrous and Leukemia--Erythroblastic--Acute

The first multicenter treatment study for AML in childhood in Germany was performed from 1978 onwards. The therapy plan was designed similar to that for the acute lymphoblastic leukaemia (ALL). The drugs with the highest efficacy in AML, cytarabine cutting catara-bine and anthracyclines, were combined during induction and consolidation, followed by preventive cranial irradiation and maintenance therapy similar to that in ALL. The remission rate of the initial study was 80%, and the 5-year survival rate increased from less than 10% before 1970 to 40%. 5 subsequent trials have further increased the 5-year survival to now 70% and even 90% in the subgroup of core-binding factor leukaemias by using an intensified and optimised treatment schedule.The AML-BFM studies were the only prospective study sequence testing the benefit of cranial irradiation. Results from study -87 including the non-randomized patients showed an increased risk of CNS and/or bone marrow relapses in non-irradiated patients. Later on there was evidence that 12 Gy resulted in the same relapse rate as 18 Gy. The AML-BFM studies always used the experience from the previous study to optimize the next study. This approach was essential together with improved supportive treatment and experience of the medical staff for the step-wise and considerable increase of longterm survival within the 6 subsequent AML-BFM studies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Cranial Irradiation; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Etoposide; Germany; Humans; Idarubicin; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Methotrexate; Multicenter Studies as Topic; Prednisone; Randomized Controlled Trials as Topic; Survival Rate; Thioguanine; Vincristine

One hundred patients were entered in a cooperative study comparing the efficacy of two different regimens in the induction treatment of acute nonlymphocytic leukemia (ANLL). Patients were randomly allocated to receive either the DAT or VAT combination; half of the patients were also randomized to receive CNS prophylaxis including intrathecal methotrexate + prednisone and cranial irradiation. Consolidation and maintenance therapy were uniform in responding patients. Out of 82 evaluable patients 41 (50%) attained complete remission (CR) with no significant difference between the two regimens. Median remission duration was slightly longer in the DAT group (32.5 vs 22 weeks); median survival was 34 weeks for all evaluable patients with no difference between the two schedules. Meningeal relapse occurred only in two patients after 19 and 99 weeks of continuous remission. Fourteen patients are still alive after 61 to greater than or equal to 155 weeks, of whom seven are in their initial remission (six in the DAT and one in the VAT group). We conclude that 1) DAT and VAT are equally effective in inducing CR in a high proportion of ANLL patients; 2) until marrow remission can be prolonged significantly, preventing CNS leukemia will not have any significant impact of the course of ANLL.

Topics: Adolescent; Adult; Antineoplastic Agents; Child; Child, Preschool; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Meningeal Neoplasms; Methotrexate; Middle Aged; Prednisone; Remission, Spontaneous; Thioguanine; Time Factors; Vincristine

To evaluate the incidence and outcome of acute myeloid leukaemia (AML), FAB M6 (erythroleukaemia).. A demographic study in the Northern Health Region of England between 1983 and 1999.. Thirty three cases were diagnosed and registered prospectively. The overall incidence was 0.077 cases/100,000/year. There was a pronounced rise in incidence in patients aged 56 years or more: 6.6 times higher than that in younger patients. Overall survival was poor; median survival was 11 months for those aged less than 56 years, and three months for patients aged 56 years and above (p = 0.045). Acquired karyotypic abnormalities were found in 17 of 27 patients where analysis was attempted. When classified according to the criteria of the Medical Research Council AML trials, karyotype predicted survival, with a median overall survival of 14 months for those with "standard risk" cytogenetic results and two months for "poor risk" results (p = 0.005).. This study demonstrates a worse survival for patients with erythroleukaemia than that reported in some published trials of selected patients.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cytarabine; Cytogenetics; Daunorubicin; England; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Leukemia, Erythroblastic, Acute; Male; Middle Aged; Prospective Studies; Risk; Survival Rate; Thioguanine; Treatment Outcome; Vidarabine

The ability of excess thymidine (10(-6)-10(-3) M) to enhance the frequency of 6-thioguanine (6-TG) resistant cell mutants and 2,6-diaminopurine (DAP) resistant cell mutants in Friend mouse erythroleukaemia cells, clone 707, was investigated. A significant increase in mutant frequency for both markers was observed at the higher (10(-4) and 10(-3) M) thymidine treatments. Measurements of deoxyribonucleoside triphosphate pool sizes in the cells revealed a dramatic elevation of the deoxythymidine triphosphate and deoxyguanosine triphosphate pools, an increase in the deoxyadenosine triphosphate pool and an almost complete disappearance of the deoxycytidine triphosphate pool at the higher thymidine treatments. This complemented the mutagenesis data. These results support the view that increases in mutant frequency may take place following perturbations in DNA precursor pools through a resultant decrease in the fidelity of DNA synthesis. Measurements of deoxyribonucleoside triphosphate pools were also carried out on clone 707 Friend cells and a thymidine kinase-deficient subclone, 707 BUF. The thymidine kinase-deficient subclone had significantly reduced deoxythymidine triphosphate and deoxyguanosine triphosphate pools relative to those observed in-clone 707 cells. The previously observed mutagen hypersensitivity in thymidine kinase-deficient Friend cells may result through pool imbalance rendering DNA excision repair error prone.

Topics: 2-Aminopurine; Animals; Cell Cycle; Cell Line; Cell Survival; Clone Cells; Deoxyribonucleotides; Drug Resistance; Friend murine leukemia virus; Leukemia, Erythroblastic, Acute; Mice; Mutagens; Mutation; Thioguanine; Thymidine

Chromosome studies of a case of erythroleukemia in a 57-year-old female patient were made from bone marrow aspirates using the fluorescent primary stain/counterstain methodology. The chromosome number ranged from 42 to 110. There was a high proportion of hypotetraploid cells and a few hypertetraploid and hypooctaploid ones. Structurally normal chromosomes varied in number from cell to cell, ranging from one to seven in the polyploid cells. A number of marker chromosomes were observed, some of which occurred repeatedly in two copies per hypotetraploid cell. The chromosomes involved in aberrations were tentatively identified as #3, #5, #7, #12, #13, #15, #16, #18, #19, and #21. In the abnormal chromosome #16, which was missing a normal short arm, a new kind of heterochromatin was demonstrated by sequential staining with DA-DAPI and DAPI-AMD, suggesting de novo amplification of an A-T-rich satellite DNA sequence.

Topics: Bone Marrow; Chromosome Banding; Cytarabine; Female; Humans; Karyotyping; Leukemia, Erythroblastic, Acute; Metaphase; Middle Aged; Polyploidy; Thioguanine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Cytarabine; Drug Combinations; Female; Humans; Leukemia, Erythroblastic, Acute; Prednisone; Thioguanine; Vincristine

13 patients with erythroleukaemia were observed between 1971-1982. The initial laboratory findings revealed normocytic anaemia with the presence of erythroblasts up to 73% of nucleated cells. The leukocyte count was normal in 5 patients, low in 5 patients and elevated in the rest. Thrombocytopenia was present in all patients. The bone marrow showed hyperplasia of erythroid series. In the majority of cases structurally abnormal erythroblasts could be found. Myeloblasts in peripheral blood and bone marrow were found at diagnosis in 12 patients. In the terminal phase, the bone marrow showed the picture of acute granulocytic leukaemia, only in one patient of acute monoblastic leukaemia. Partial remission was obtained in 6 patients, the rest did not respond to any protocol. Survival time amounted to 2 to 30 months after diagnosis.

Topics: Adrenal Cortex Hormones; Adult; Aged; Asparaginase; Blood Cell Count; Bone Marrow Examination; Cytarabine; Female; Humans; Leukemia, Erythroblastic, Acute; Male; Middle Aged; Neoplastic Stem Cells; Thioguanine; Vincristine

A monoclonal antibody (LICR.LON.R10) specific for the major sialoglycoprotein of the erythroid cell membrane, glycophorin A (alpha), has been used to test the possibility that "cryptic" erythroleukemia may be diagnosed as acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML). In addition to 27 overt erythroleukemias, 724 leukemias, including 329 ALL (103 in relapse), 205 AML, and 109 blast crises of Ph1-positive chronic myeloid leukemia, were analyzed. Twenty cases with a significant proportion of glycophorin-A-positive (gA+) cells were found; 8 of these (5 AML and 3 blast crises of chronic myeloid leukemia, CML) had an obvious erythroid component, but 12 others were diagnosed as AML (2), AMML (1), CML in myeloid blast crisis (4) or megakaryoblastic blast crisis (1), acute megakaryoblastic leukemia (2), or acute lymphoblastic leukemia (2). The latter two patients had no immunologic evidence supporting a diagnosis of ALL and were resistant to chemotherapy. We conclude that AML and ALL only very rarely express gA, and these are probably genuine "cryptic" erythroleukemias. Other gA+ leukemias (megakaryoblastic and CML blast crises) may arise from bi- or pluripotent stem cells and contain distinct and separable blast cell populations.

Topics: Antibodies, Monoclonal; Cytarabine; Daunorubicin; Female; Glycophorins; Humans; Infant; Leukemia, Erythroblastic, Acute; Sialoglycoproteins; Thioguanine

A case is reported of a 12-year-old boy with Di Guglielmo's syndrome who achieved complete remission for over three years before developing a central nervous system relapse. The poor results of treatment in this disease are reviewed and the arguments for routine central nervous system prophylaxis discussed.

Topics: Antineoplastic Agents; Child; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Erythroblastic, Acute; Male; Meningeal Neoplasms; Prednisolone; Thioguanine; Time Factors

Wild type Friend erythroleukaemia cells (clone 707) and thymidine kinase (EC. 2.7.1.2.1) deficient derivatives were examined for sensitivity to killing by ultra-violet (UV) irradiation. Deficiency of thymidine kinase leads to increased cell killing as evidenced in all of twelve thymidine kinase deficient clones examined. A revertant thymidine kinase positive clone was found to have a level of thymidine kinase activity and UV sensitivity intermediate between wild type cells and its thymidine kinase deficient parent clone. The increased cell killing in thymidine kinase deficient clones is also reflected in increased mutagenesis by UV to 6-thioguanine resistance. It is suggested that the increased mutagenesis and sensitivity is due to defective DNA repair as a result of an imbalance in deoxyribonucleoside triphosphate pools in thymidine kinase deficient cells.

Topics: Animals; Cell Line; Cell Survival; Clone Cells; DNA Repair; Drug Resistance; Leukemia, Erythroblastic, Acute; Mice; Mutation; Thioguanine; Thymidine Kinase; Ultraviolet Rays

The effect of hemin on the differentiation program of murine erythroleukemia (MEL) cells has been investigated. While hemin treatment does induce increased levels of globin mRNA and hemoglobin, it fails to lead to other biochemical changes associated with MEL cell differentiation induced by DMSO and thioguanine. These include increased levels of the nuclear protein IP25 and of the enzyme cytidine deaminase. Clonal analysis of hemin-treated cells revealed that unlike other inducers, hemin does not cause a reprogramming of MEL cells to a specific limitation of proliferative capacity. These observations suggest that hemin differs from DMSO and thioguanine in that it exerts specific effects on globin expression in MEL cells without triggering commitment to the terminal differentiation program.

Topics: Animals; Cell Differentiation; Cell Line; Dimethyl Sulfoxide; Globins; Heme; Hemin; Hemoglobins; Leukemia, Erythroblastic, Acute; Leukemia, Experimental; Mice; RNA, Messenger; Thioguanine

The need for prophylactic therapy of the central nervous system in adult acute nonlymphoblastic leukemia has been suggested but no proven. Over a 4-year period from January 1973, to December 1976, we have maintained 40 patients achieving complete remission on a regimen consisting of monthly courses of Cytosine Arabinoside and 6-thioguanine. Twenty patients remain in remission with a predicted median remission duration for the entire group of 14.5 months. Thirty nine of the patients did not have central nervous system leukemia at diagnosis, and only one of these patients (2.6%) has had remission tenance regimen there is little need for central nervous system prophylaxis in adult acute nonlymphoblastic leukemia.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Brain Neoplasms; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Remission, Spontaneous; Thioguanine

The results of treatment of 57 patients suffering from acute non-lymphoid leukemia by two protocols are compared. The more aggressive Coap protocol rendered a higher remission rate (57.1%), than the mild Guyer protocol where the remission rate has been 25%. The best results have been achieved in the former group in the younger population; in the latter group there has been no age-effect relationship. Although the remission rate differed in both protocols there has been no statistically significant difference in survival.

Topics: Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Middle Aged; Prednisone; Prognosis; Thioguanine; Vincristine

Topics: Anemia, Pernicious; Blood Cell Count; Bone Marrow Cells; Cytarabine; Cytoplasm; Follow-Up Studies; Hematologic Diseases; Humans; In Vitro Techniques; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Megakaryocytes; Mercaptopurine; Plasmacytoma; Polycythemia; Thioguanine; Thrombocytopenia

Topics: Adolescent; Adult; Aminosalicylic Acids; Asparaginase; Blood Cells; Bone Marrow; Bone Marrow Cells; Daunorubicin; Diagnosis, Differential; Doxorubicin; Esterases; Histocytochemistry; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Methotrexate; Middle Aged; Peroxidases; Prednisolone; Thioguanine; Vincristine

Topics: Adult; Age Factors; Aged; Antineoplastic Agents; Bone Marrow Cells; Carmustine; Chromosome Aberrations; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitosis; Nitrosourea Compounds; Prednisone; Prognosis; Thioguanine; Time Factors; Vincristine

Topics: Aged; Ampicillin; Bone Marrow; Bone Marrow Cells; Carbamates; Cephaloridine; Cyclophosphamide; Cytarabine; Daunorubicin; Environmental Exposure; Humans; Imines; Insecticides; Leukemia, Erythroblastic, Acute; Lysosomes; Macrophages; Male; Microscopy, Electron; Mitochondria; Pneumonia; Prednisone; Sulfides; Tetracycline; Thioguanine; Vincristine

Topics: Bone Marrow Cells; Bone Marrow Transplantation; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Erythroblastic, Acute; Prednisone; Remission, Spontaneous; Thioguanine; Time Factors; Transplantation, Homologous

A preliminary report is given of a trial of the T.R.A.P. regimen (thioguanine, rubidomycin, cytosine arabinoside, and prednisolone) for the treatment of acute myeloid leukaemia. Out of 27 patients treated 13 (48.1%) obtained complete remission. The treatment was well tolerated and produced especially good results in elderly patients.

Topics: Adolescent; Adult; Age Factors; Aged; Child; Cytarabine; Daunorubicin; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; London; Middle Aged; Prednisolone; Remission, Spontaneous; Thioguanine

Topics: Acute Disease; Adolescent; Adult; Aged; Bacterial Infections; Cytarabine; Drug Combinations; Female; Hemorrhage; Humans; Hydroxyurea; Length of Stay; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Patient Isolators; Prednisone; Remission, Spontaneous; Thioguanine