thioguanine-anhydrous and Anemia--Aplastic

The results of four consecutive trials designed by the GIMEMA group for the treatment of ANLL in elderly patients are reviewed. Complete remission (CR) has been achieved in 20.8% of patients older than 60 years treated with 5-day courses of ARA-C plus thioguanine, in 22.7% of patients treated with high dose ARA-C (HDARAC) plus Asparaginase, in 39.5% of patients aged 55 to 80 receiving either Idarubicin or Daunorubicin in combination with Cytarabine in a standard 3+7 protocol and in 51% of patients older than 60 years treated with intermediate dose ARA-A (IDARAC) plus Mitoxantrone. From 1988, patients ineligible for aggressive chemotherapy entered a study of palliative treatment with Thioguanine and ARA-C. This 18 year GIMEMA experience showed that: CR can be obtained only with regimens producing marrow aplasia, the inclusion of anthracyclines or Mitoxantrone improves the CR rate, without prohibitive toxicity, haematological toxicity is very high in elderly patients and account for the most frequent cause of treatment failure namely death in aplasia, palliative treatment does not improve the quality of life and prolongs median survival only slightly. When comparing the results of these trials, it appears that in the GIMEMA group the capability of offering effective treatment to elderly patients with ANLL has continuously improved and that IDARAC plus Mitoxantrone is so far the most active and best tolerated regimen. Death in aplasia remains a major problem and future trials will be aimed at exploiting the possibility of reducing the haematological toxicity by using recombinant colony stimulating factors.

Topics: Age Factors; Aged; Aged, 80 and over; Anemia, Aplastic; Antineoplastic Combined Chemotherapy Protocols; Cause of Death; Cytarabine; Daunorubicin; Drug Administration Schedule; Feasibility Studies; Humans; Idarubicin; Infusions, Intravenous; Italy; Leukemia, Myeloid, Acute; Middle Aged; Mitoxantrone; Remission Induction; Thioguanine

The study included 68 children aged from 1 to 16 years treated for acute leukemias and bone marrow aplasia. Cytomegalovirus antigen (CMV) was detected by immunofluorescence in urinary sediment cells and in cell cultures after their inoculation with CMV. Besides, the activity of IgG and IgM classes of antibodies against CMV was determined. Presence of one or more markers of CMV infection was demonstrated in 31 children, i.e., 45.5%. In eight children (11.7%) clinical manifestation of CMV infection were demonstrable with fever, hepatitis, pneumonia, rash. In all the children who completed the treatment with hyperimmune globulin, regression of clinical symptoms and signs of CMV infection with the elimination of virus antigen from urine was achieved.

Topics: Adolescent; Anemia, Aplastic; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Cytomegalovirus Infections; Daunorubicin; Female; gamma-Globulins; Humans; Immune Tolerance; Immunization, Passive; Infant; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Male; Methotrexate; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Thioguanine; Vincristine

The induction of mutants at the hypoxanthine-guanine phosphoribosyltransferase and Na+/K+ ATPase loci by photoaddition of two bifunctional psoralens was compared in normal and in Fanconi's anemia lymphoblasts from the genetic complementation group A. For the two loci, the frequency of mutants was significantly lower in Fanconi's anemia than in normal cells. This is true whether the data are expressed as a function of dose or as a function of survival level. It is suggested that the chromosomal instability characteristic of Fanconi's anemia is responsible for the cancer proneness rather than the mutability at the gene level.

Topics: Anemia, Aplastic; Cell Survival; Fanconi Anemia; Furocoumarins; Humans; Hypoxanthine Phosphoribosyltransferase; Methoxsalen; Mutation; Sodium-Potassium-Exchanging ATPase; Thioguanine; Trioxsalen; Ultraviolet Therapy

One hundred ninety-six patients with acute myelogenous leukemia (AML) were treated with intensive induction chemotherapy using similar daunorubicin/cytarabine/thioguanine regimens. Treatment results of 44 patients who had a documented preleukemic syndrome or cytopenia present for more than 2 months before developing over AML were compared with 152 patients with de novo AML. Eighteen (41%) patients with preleukemia evolving into AML achieved complete remission compared with 111 (73%) patients with de novo AML (P less than .01). Patients with preleukemia-AML had a significantly longer period to recovery of granulocytes. Multivariate analysis indicated that presence of a previous preleukemic syndrome and advancing age were independent poor prognostic indicators for achieving remission. For patients who achieved remission, disease-free survival and overall survival were also inferior for patients with previous preleukemia; disease-free survival was 17 +/- 17% at 3 years compared with 29 +/- 10% in patients with de novo AML (P = .02). These data indicate that intensive chemotherapy has limited efficacy in patients with AML following a preleukemic syndrome. Durable remissions may be achieved in some patients.

Topics: Age Factors; Anemia, Aplastic; Anemia, Refractory, with Excess of Blasts; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute; Multivariate Analysis; Neural Tube Defects; Preleukemia; Prognosis; Regression Analysis; Survival Rate; Thioguanine

The incidence of spontaneous 6-thioguanine-resistant (TGr) lymphocytes was studied in the peripheral blood collected from seven Fanconi anemia (FA) patients and five of their heterozygous parents using an autoradiographic or a lymphocyte cloning method. Five of the seven patients showed a significantly elevated incidence of TGr lymphocytes as compared to age- and sex-matched healthy controls. There was, however, no difference between FA heterozygotes and controls. These results suggest some variability among the patients similar to those reported in clinical and cytogenetic investigations. The basis for the increase in TGr cells in the patients is not known, but the inherent genomic instability reflected as increased frequencies of chromosomal aberrations is one possible explanation.

Topics: Adolescent; Adult; Anemia, Aplastic; Autoradiography; Child; Child, Preschool; Chromosome Aberrations; Drug Resistance; Fanconi Anemia; Female; Heterozygote; Humans; Lymphocytes; Male; Mutation; Thioguanine

Fanconi anemia (FA) fibroblasts are known to be exceptionally sensitive to the cytotoxic action of mitomycin C (MMC). The survival of FA cells was enhanced significantly when 0.5 mM caffeine or 0.5 mM adenine was added for 72 h after the cells were exposed to MMC. In other experiments in which MMC was not used, FA fibroblasts were shown to be significantly more sensitive than control cells to 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), and 6-azauridine (6-AU). These observations offer a new approach to defining the basic biochemical defect in FA.

Topics: Anemia, Aplastic; Ataxia Telangiectasia; Azauridine; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Fanconi Anemia; Humans; Mercaptopurine; Mitomycins; Skin; Thioguanine

Topics: Anemia, Aplastic; Antineoplastic Agents; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Humans; Leukemia, Myeloid; Methylprednisolone; Thioguanine

The role of the ABO blood group system in determining the outcome of bone marrow transplantation was investigated in 53 patients with aplastic anemia and acute leukemia grafted from HLA-identical siblings. There was no correlation between ABO compatibility and marrow engraftment, graft rejection, or graft-versus-host disease. In 5 recipients with antibodies prior to transplantation to antigens of the ABH system present on the cells of their donors, plasma exchange and antibody absorption in vivo were effective in permitting engraftment of ABO-incompatible bone marrow. These findings indicate that the ABO system is not a clinically significant barrier to successful bone marrow transplantation in otherwise histocompatible individuals.

Topics: ABO Blood-Group System; Adolescent; Adult; Anemia, Aplastic; Antilymphocyte Serum; Bone Marrow Cells; Bone Marrow Transplantation; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Graft Rejection; Graft vs Host Disease; Histocompatibility; Humans; Immunosuppression Therapy; Isoantibodies; Leukemia; Male; Thioguanine; Transplantation Immunology; Transplantation, Homologous

Topics: Aged; Anemia, Aplastic; Arsenic; Arsenic Poisoning; Autopsy; Biopsy; Bone Marrow Cells; Cytarabine; Environmental Exposure; Humans; Klebsiella Infections; Leukemia, Myeloid, Acute; Male; Oxymetholone; Penicillamine; Pesticides; Poisoning; Prednisone; Recurrence; Sepsis; Thioguanine

Topics: Anemia, Aplastic; Bone Marrow Examination; Cell Nucleus; Child; Cytarabine; Erythrocytes; Erythropoiesis; Humans; Leukemia, Myeloid, Acute; Male; Megakaryocytes; Methotrexate; Mitosis; Reticulocytes; Thioguanine