thioguanine-anhydrous and Multiple-Myeloma

In the prospective phase 3 HOVON-50/GMMG-HD3 trial, patients randomized to TAD (thalidomide, doxorubicin, dexamethasone) had a significantly higher response rate (at least PR) after induction compared with patients randomized to VAD (vincristine, adriamycin, dexamethasone, 72% vs. 54%, p<0.001). Complete remission (CR) and very good partial remission (VGPR) were also higher after TAD. After High Dose melphalan 200mg/m(2) response was comparable in both arms, 76% and 79% respectively. However, CR plus VGPR were significantly higher in the patients randomized to TAD (49% vs. 32%, p<0.001). CTC grade 3-4 adverse events were similar in both arms.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Dexamethasone; Female; Humans; Male; Medical Oncology; Middle Aged; Multiple Myeloma; Remission Induction; Thalidomide; Thioguanine; Treatment Outcome; Vincristine

Peripheral blood stem cell (PBSC) transplantation gives rapid recovery of neutrophils and platelets and sustained haemopoiesis. However in patients with acute myeloid leukaemia (AML) platelet recovery has a distinctive rapid rise and then secondary fall between 3 to 8 weeks post-transplant. This study compares platelet and neutrophil recovery after PBSC transplantation in 15 patients with AML and 29 patients with other diseases consecutively transplanted in a single unit. PBSC were collected during recovery from consolidation chemotherapy in AML patients and after cyclophosphamide or cytokine administration in the other patient groups. Mononuclear cell numbers collected were similar but CFU-GM numbers were greater from the AML patients. A significant secondary fall occurred only in the platelet count and only in AML patients. Long-term recovery of the platelet count was the same in AML as in the other patients. In AML patients, the fall was the same in the long term remitters as in those who eventually relapsed. Previous studies have not, demonstrated a difference in type of precursors mobilized by differing methods, but have not included AML patients. Megakaryocyte precursors were assayed in this study and showed no consistent differences in number between patient groups however pre-progenitor assays are not yet established especially in the megakaryocytic lineage. The possible explanation for this secondary fall in AML patients is discussed.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Bone Marrow; Cell Differentiation; Cell Lineage; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Female; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Leukemia, Myeloid; Lymphoma, Non-Hodgkin; Male; Megakaryocytes; Multiple Myeloma; Ovarian Neoplasms; Platelet Count; Thioguanine; Time Factors

The association of acute leukemia and multiple myeloma (MM) has been usually described not only as a complication of chemotherapy but also in the absence of chemotherapy or together at the time of diagnosis. Such leukemias are typically acute myeloid leukemia (AML). The myelomonocytic subtype is particularly found.. We report a case of a 68-year-old female who developed AML 2 years after the diagnosis of light chain (kappa) myeloma. She had been treated with oral melphalan and prednisone for MM. The patient was treated with an anthracycline-lacking therapy consisting of etoposide 120 mg/m2, thioguanine 100 mg/m2 orally twice daily on 1-5 days, and cytarabine 40 mg/m2 subcutaneously on day 1 (ETC) because of poor cardiac performance.. Following ETC therapy our particular patient has been in complete hematologic remission for 29 months. This therapy might be a safe alternative in secondary leukemia especially for elderly patients.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Drug Administration Schedule; Etoposide; Female; Humans; Injections, Subcutaneous; Leukemia, Myeloid, Acute; Multiple Myeloma; Remission Induction; Thioguanine

Topics: Animals; Antibodies, Monoclonal; B-Lymphocytes; Cell Division; Cell Fusion; Cell Line, Transformed; Chromosomes, Human; Culture Media; Hepatitis B Antibodies; Hepatitis B Core Antigens; Herpesvirus 4, Human; Humans; Hybrid Cells; Hybridomas; Hypoxanthine Phosphoribosyltransferase; Immunoglobulin M; Mice; Multiple Myeloma; Ouabain; Recombinant Proteins; Selection, Genetic; Thioguanine; Tumor Cells, Cultured

Thirty-three patients with relapsing or refractory multiple myeloma were treated with 6-Thioguanine (6TG) at a dose of 1 g/M2, with therapy given over four hours every three weeks. The major toxicity seen was myelotoxicity; thrombocytopenia was more commonly noted than neutropenia. One patient achieved a PR, two were clinically improved. 6TG in this short infusion schedule proved to be myelotoxic, but demonstrated little activity in previously treated myeloma patients.

Topics: Drug Evaluation; Humans; Infusions, Intravenous; Multiple Myeloma; Thioguanine

An Epstein-Barr-virus-transformed lymphoblastoid cell line (ECEBV) was derived from a multiply transfused renal dialysis patient. ECEBV was shown to secrete specific antibody in a cellular enzyme-linked immunosorbent assay (CELISA) and was hybridized with the mutagenized human fusion partner G M1500 resistant to 6-thioguanine and ouabain. Hybridomas surviving hypoxanthine-aminopterin-thymidine (HAT) and ouabain selection were cloned by limiting dilution. The hybridomas continue to secrete antibody which reacts with some human cells but not with others after 14 months in culture. None reacts with K562 (no HLA-A, -B, -C or -DR) or with Daudi (no HLA-A, -B, or -C). This is a preliminary report of the production of a human monoclonal antibody to HLA. Application of this technique could result in the large-scale production of human monoclonal antibodies for HLA typing, the production of anti-idiotype antibodies for use in transplant patients to prevent acute rejection, and for the study of the structure and function of HLA in man.

Topics: Antibodies, Monoclonal; Cell Line; Cell Transformation, Viral; Drug Resistance; Enzyme-Linked Immunosorbent Assay; Herpesvirus 4, Human; HLA Antigens; Humans; Hybridomas; Lymphocytes; Multiple Myeloma; Ouabain; Thioguanine

Topics: Animals; Antigens; Antigens, Neoplasm; Cell Differentiation; Cell Line; Cell Membrane; Cell Survival; Clone Cells; Cyclic AMP; Hydrocortisone; Immune Sera; Iodine Radioisotopes; Lectins; Lymphoma; Mice; Multiple Myeloma; Protein Binding; Thioguanine; Thymidine

Topics: Animals; Antineoplastic Agents; Female; Mice; Mice, Inbred Strains; Multiple Myeloma; RNA Nucleotidyltransferases; Templates, Genetic; Thioguanine

Topics: Adult; Bronchopneumonia; Cytarabine; Humans; Leukemia, Myeloid, Acute; Male; Melphalan; Multiple Myeloma; Plasmacytoma; Thioguanine

Topics: Adult; Aged; Azaserine; Drug Synergism; Female; Humans; Male; Middle Aged; Multiple Myeloma; Thioguanine

Topics: Alkylating Agents; Antineoplastic Agents; Biomedical Research; Blood Chemical Analysis; Bone Marrow; gamma-Globulins; Geriatrics; Multiple Myeloma; Thioguanine; Toxicology