thioguanine-anhydrous and Hodgkin-Disease

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Evaluation; Drug Resistance; Etoposide; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Melphalan; Neoplasm Recurrence, Local; Neoplasms; Thioguanine; Transplantation, Autologous

Approximately half of conventional-chemotherapy-resistant, far-advanced Hodgkin's disease patients can be placed into remission with existing intensive therapy regimens and ABMT; these results are similar to those noted in less-heavily pretreated non-Hodgkin's lymphoma patients. While a few of these end-stage patients have prolonged remissions, failure frequently occurs in a pattern that suggests the inadequacy of the intensive regimens rather than reinoculation of malignant cells in the marrow autograft. The use of additional local radiotherapy may be helpful in selected patients, and more effective regimens may be developed in the future. However, treatment of less advanced disease is primarily indicated. Due to previous treatment features, patients with advanced Hodgkin's disease may have more morbidity and mortality than a similar group of non-Hodgkin's lymphoma patients. This problem can be minimized by better patient selection, earlier marrow storage and the avoidance of TBI-containing regimens in patients at high risk of interstitial pneumonitis. Routine marrow purging is unlikely to be required for Hodgkin's disease patients given ABMT. The use of intensive therapy and ABMT for the treatment of Hodgkin's disease is currently indicated most clearly for treatment of a patient in initial partial remission, early relapse from an initial chemotherapy-induced remission, or consolidation of a second remission reinduced by conventional therapy.

Topics: Alkylating Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Transplantation; Carmustine; Cell Separation; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Resistance; Etoposide; Hodgkin Disease; Humans; Lomustine; Pulmonary Fibrosis; Risk; Thioguanine; Transplantation, Autologous; Whole-Body Irradiation

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Evaluation; Drug Resistance; Etoposide; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma; Melphalan; Neoplasm Recurrence, Local; Neoplasms; Thioguanine; Transplantation, Autologous

The clinical picture and results of treating malignant lymphoma in children, diagnosed and treated at the Pediatric Institute of Pomeranian Medical Academy in Szczecin during the period between May 1979 and February 1992, were analyzed. The studied group consisted of 33 children (23 boys, 10 girls) aged between 41-169 months (median 112 months, mean 110 months) having Hodgkin's lymphoma (HL), and 35 children (26 boys, 9 girls), aged between 35-171 months (median 101 months, mean 104 months), with non-Hodgkin's lymphoma (NHL). Till 1987 the children with HL were treated according to MOPP program, and since 1988 with MVPP/B-DOPA. Two children were treated according to COMP and ABVD programs. The NHL children were treated till 1985 with LSA2L2 or COAMP, and from 1986 with BFM-NHL 86 with the modification of methotrexate doses. The duration of observation involving HL cases ranged from 2 to 156 months (median 76, mean 78 months), that covering NHL cases from 3 to 153 months (median 28 months, mean 44 months). It was proved that the results of HL treatment in the Pediatric Institute of Pomeranian Medical Academy in Szczecin were comparable with the results of other centers. The probability of event free survival (EFS) for the whole group was 0.818, for children treated by MOPP program was 0.888, for children with MVPP/B-DOPA was 0.900. Unfortunately, the results of NHL treatment in our center in Szczecin are worse than those of other hematologic-oncologic institutions. The EFS was 0.550. The reason why our results were poor in treating NHL in our center was: delay in beginning the remission-inducing treatment because of diagnostic difficulties (especially in smaller hospitals): prolongation of the first remission-inducing therapy over 14 days, mainly due to generalized infection, generalized diathesis haemorrhagica with bleeding from the alimentary tract, and finally the need of modifying the treatment program BFM 86 concerning primarily the lowering of methotrexate doses from 5 g/m2 to 0.5 g/m2. That was necessary in view of our inability of monitoring the level of methotrexate in blood. All of those findings suggest the necessity of: 1) earlier proper diagnosis; the physicians taking care of children should be aware of high incidence of such neoplasms in children, especially with atypical clinical presentation; 2) full realization of the therapeutic program (particularly remission-inducing one). A general real improvement of the treatment conditions in hospi

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Bleomycin; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Dacarbazine; Disease-Free Survival; Doxorubicin; Female; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Mechlorethamine; Methotrexate; Prednisolone; Prednisone; Procarbazine; Prognosis; Risk Factors; Thioguanine; Vinblastine; Vincristine

Currently no treatment has proved successful in inducing ovarian steroidogenic and/or gametogenic recovery in patients with haematological malignancies treated by cytotoxic chemotherapy once biochemical failure becomes manifest i.e., when FSH levels exceed 40 IU/L. This paper reports two such cases with classical biochemical ovarian failure in which ovarian function was induced by brief stimulation with Human Menopausal Gonadotrophin (HMG).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Carmustine; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Female; Follicle Stimulating Hormone; Hodgkin Disease; Humans; Leukemia, Myelomonocytic, Acute; Luteinizing Hormone; Melphalan; Menotropins; Ovulation Induction; Podophyllotoxin; Prednisone; Pregnancy; Pregnancy, Multiple; Primary Ovarian Insufficiency; Remission Induction; Teniposide; Thioguanine; Vincristine

Four patients developed clinically important portal hypertension with histological features of idiopathic portal hypertension while they were receiving cytotoxic drugs for chronic myeloid leukaemia and Hodgkin's disease. Mild sclerosis of some small portal triads was the only abnormality seen at light microscopical examination in three of the four cases. In the remaining case light microscopical findings seemed to be normal. Two cases examined by electron microscopy showed perisinusoidal fibrosis; in one case this was the only abnormality detected. There is an association between idiopathic portal hypertension and the use of chemotherapeutic agents, particularly thioguanine. Adequate histological examination of liver tissue, including electron microscopic studies, is recommended for patients who develop hepatic problems while receiving cytotoxic treatment to elucidate this problem.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Female; Hodgkin Disease; Humans; Hypertension, Portal; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Liver; Liver Cirrhosis; Male; Microscopy, Electron; Middle Aged; Thioguanine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cytarabine; Dacarbazine; Daunorubicin; Doxorubicin; Hodgkin Disease; Humans; Leukemia, Myeloid; Leukemia, Radiation-Induced; Male; Mechlorethamine; Prednisone; Procarbazine; Radiotherapy; Thioguanine; Vinblastine; Vincristine

This paper describes a prospective study and a simultaneous longitudinal study of the frequency of 6-thioguanine- (6TG-) resistant peripheral blood lymphocytes in children with cancer and in controls. Thioguanine resistance was measured autoradiographically by the ability of phytohemagglutinin-stimulated lymphocytes to incorporate tritiated thymidine in the presence or absence of 2 x 10(-4) or 2 x 10(-5) M 6TG. 5 of 29 untreated cancer patients had higher frequencies of 6TG-resistant lymphocytes than any of 116 controls. Patients receiving chemotherapy or radiation therapy showed significantly higher numbers of 6TG-resistant lymphocytes than controls, and in rare patients abnormally high frequencies of 6TG-resistant cells persisted after therapy was discontinued. Among 22 patients studied prospectively before and during therapy, the frequency of 6TG-resistant lymphocytes was significantly higher during therapy. From these results we conclude (1) that some cancer patients have abnormally high frequencies of 6TG-resistant lymphocytes, and (2) cancer therapy either causes selection of 6TG-resistant cells or causes a phenotypic or genotypic change leading to further increases in frequencies of 6TG resistance.

Topics: Adult; Cells, Cultured; Child; Drug Resistance; Hodgkin Disease; Humans; Lymphocyte Activation; Lymphocytes; Reference Values; Rhabdomyosarcoma; Sarcoma, Ewing; Thioguanine

Lymphocytes from healthy young adults and from adolescent patients with cancer were examined for their ability to incorporate [3H]thymidine in short-term culture in the presence of phytohemagglutinin and 6-thioguanine (6-TG). The numbers of labeled nuclei after 72 h in culture were compared to numbers of labeled nuclei after 30 h in culture. The numbers of labeled nuclei in the presence of 6-TG increased 6-65-fold between 30 and 72 h. The increases in number could be accounted for by 3-6 cycles of cell division. The data suggest that 6-TG-resistant peripheral blood lymphocytes are capable of reproduction in short-term culture, but factors other than reproduction may also contribute to increases in numbers of 6-TG-resistant cells.

Topics: Adult; Cells, Cultured; Drug Resistance; Hodgkin Disease; Humans; Lymphocyte Activation; Lymphocytes; Mitotic Index; Reference Values; Rhabdomyosarcoma; Sarcoma, Ewing; Thioguanine

Topics: Asparaginase; Child; Cyclophosphamide; Cytosine; Daunorubicin; Doxorubicin; Drug Therapy, Combination; Hodgkin Disease; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Melphalan; Mercaptopurine; Methotrexate; Neoplasms; Nitrogen Mustard Compounds; Osteosarcoma; Prednisone; Procarbazine; Prognosis; Remission, Spontaneous; Rhabdomyosarcoma; Teniposide; Thioguanine; Vincristine; Wilms Tumor

Topics: Antineoplastic Agents; Asparaginase; Cell Division; Chemistry; Culture Techniques; Cytarabine; Daunorubicin; Depression, Chemical; DNA; Drug Combinations; Drug Resistance; Germ-Free Life; Half-Life; History, 20th Century; Hodgkin Disease; Humans; Leukemia; Lymphatic Diseases; Mercaptopurine; Remission, Spontaneous; Stimulation, Chemical; Thioguanine