thioguanine-anhydrous and Testicular-Neoplasms

Testicular relapse of acute myeloid leukemia without bone marrow involvement is a rare event. We describe a case of an 18-year-old male who had an isolated testicular relapse 86 months (7.2 years) from original diagnosis. He was treated with surgery only, without adjuvant therapy. The patient then developed central nervous system involvement 9 months later. Fluorescence in situ hybridization and immunohistochemistry were used to establish the diagnosis of a relapse rather than a new leukemic process. He was treated with intrathecal chemotherapy and systemic reinduction, followed by a stem cell transplant. This patient had a 7.2-year period between original diagnosis and the testicular relapse of acute myeloid leukemia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Child; Cytarabine; Daunorubicin; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Injections, Spinal; Leukemia, Myeloid, Acute; Male; Neoplasm Recurrence, Local; Testicular Neoplasms; Thioguanine; Treatment Outcome

Testicular germ-cell cancer (TGCC) patients are at risk of developing hypogonadism but no risk factors have yet been defined.. Blood was collected from 143 TGCC patients (after orchidectomy, prior to further therapy (T0) and 6, 12, 24, 36 and 60 months (T6, T12, T24, T36 and T60) after therapy). Biological hypogonadism (BH) was defined as: serum testosterone below 10 nmol/l and/or LH >10 IU/l; odds ratios (ORs) for BH with BH at T0, age, stage of disease, testicular characteristics, and androgen receptor polymorphism as predictors were calculated as well as the OR for developing BH post-treatment (one to two cycles of adjuvant chemotherapy (ACT) versus three to four cycles of higher dose chemotherapy (HCT) versus adjuvant radiotherapy (RT)).. HCT increased the OR for BH at T6 (OR 22, 95% confidence interval (CI) 4.4-118) and T12 (OR 5.8, 95% CI 1.5-22). RT increased the OR at T6 (OR 10, 95% CI 2.1-47) and at T12 (OR 3.9, 95% CI 1.1-14). Microlithiasis predicted BH at T0 (OR 11, 95% CI 1.2-112), T12 (OR 3.9, 95% CI 1.1-13), T24 (OR 3.0, 95% CI 1.0-8.8), T36 (OR 5.4, 95% CI 1.7-17) and T60 (OR 4.4, 95% CI 1.2-16). BH at T0 was a risk for BH at T6 (OR 53, 95% CI 19-145), T12 (OR 125, 95% CI 37-430), T24 (OR 88, 95% CI 26-300) and T36 (OR 121, 95% CI 32-460).. It is clinically relevant that BH at T0 and testicular microlithiasis were predictive factors for post-treatment BH. HCT and RT gave temporary BH.

Topics: Adult; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Cytarabine; Doxorubicin; Follow-Up Studies; Humans; Hypogonadism; Lithiasis; Longitudinal Studies; Male; Neoplasms, Germ Cell and Embryonal; Orchiectomy; Prospective Studies; Radiation Injuries; Radiotherapy; Radiotherapy, Adjuvant; Risk Factors; Testicular Diseases; Testicular Neoplasms; Testosterone; Thioguanine

Metastatic nonseminomatous testicular germ cell tumors are curable using combination chemotherapy in approximately 80% of patients. In contrast, most other patients with other types of cancer either present with or acquire drug-resistant disease following chemotherapy. Cell lines derived from testis tumors retain hypersensitivity to both drugs and radiation in vitro, thus providing a model system with which to investigate the genetic basis of hypersensitivity to these agents. This study compared the spontaneous and both ethyl methanesulfonate- and cisplatin-induced frequencies of mutation of 6-thioguanine resistance in 3 human bladder and 3 testis tumor cell lines and a bladder and a testis cell line with cisplatin resistance induced in vitro. The two tumor types showed similar frequencies of both spontaneous and induced mutation frequencies at this locus. Therefore, we failed to provide evidence for the hypothesis that the curability of testis tumors is associated with a low frequency of mutation to drug resistance.

Topics: Antineoplastic Agents; Cisplatin; DNA; Dose-Response Relationship, Drug; Drug Resistance; Ethyl Methanesulfonate; Humans; Hypoxanthine Phosphoribosyltransferase; In Vitro Techniques; Male; Mutation; Testicular Neoplasms; Thioguanine; Urinary Bladder Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Cranial Irradiation; Cytarabine; Daunorubicin; Doxorubicin; Humans; Hydrocortisone; Leukemia, Monocytic, Acute; Male; Meningeal Neoplasms; Mercaptopurine; Methotrexate; Prednisone; Remission Induction; Testicular Neoplasms; Thioguanine