thioguanine-anhydrous and Lymphoma--Large-B-Cell--Diffuse

Two hundred and ninety-eight evaluable patients with non-Hodgkin's lymphoma were stratified according to histology, treated with either BCNU, cyclophosphamide, Oncovin (vincristine), and prednisone (BCOP) or cyclophosphamide, Oncovin (vincristine), and prednisone (COP), and evaluated at 3 months. Those with a good partial (PR) or complete response (CR) were then separated and randomized to be treated with either cycle-active therapy (methotrexate, cytosine arabinoside, and 6-thioguanine) or more induction therapy with COP or BCOP. Patients not achieving a good PR at 3 months received cycle-active therapy. The results indicate (a) that there is a significant advantage for good over poor histologies with regard to good PRs at 3 months; (b) that the addition of cycle-active therapy (as administered in this study) is of advantage when the tumor has been significantly reduced only for patients receiving COP induction; and (c) that BCOP has an advantage over COP in diffuse histiocytic lymphoma where the percentage of CRs, their durability, and subsequent survival are superior for patients treated with BCOP. Since this lymphoma accounts for about 25% of all non-Hodgkin's lymphoma patients, this regimen represents a useful tool for the chemotherapist.

Topics: Carmustine; Cell Cycle; Clinical Trials as Topic; Cyclophosphamide; Cytarabine; Drug Therapy, Combination; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Methotrexate; Prednisone; Prognosis; Remission, Spontaneous; Thioguanine; Time Factors; Vincristine

Primary lymphoma of the bones (PLB) is a rare extranodal non-Hodgkin lymphoma (NHL) that is particularly rare in children. The clinical presentation and radiological features of PLB are often nonspecific, making clinical diagnosis challenging and misdiagnosis frequent. Here, we report 2 children with PLB focusing on clinical presentation, differential diagnosis, and treatment outcomes.. A 9-year-old boy presented with left knee swelling and pain for 4 months after a fall. He was previously misdiagnosed with traumatic soft tissue injury. The second patient was an 11-year-old boy with a 6-month history of intermittent left knee pain. He was previously misdiagnosed with bone tuberculosis and chronic osteomyelitis.. A 9-year-old boy showed an abnormal signal of the left tibia metaphysis, diaphysis, and epiphysis, and tibia with periosteal reactions and surrounding soft tissue swelling. Tumor biopsy and immunohistochemistry confirmed a diagnosis of B-cell lymphoblastic lymphoma.An 11-year-old boy showed a permeative lesion in the metaphysis and diaphysis of the left proximal tibia. Tumor biopsy and immunohistochemistry confirmed the diagnosis of diffuse large B-cell lymphoma.. Both patients were treated with 6 courses of NHL-Berlin-Frankfurt-Münster-95.. Both patients are in complete clinical remission with a follow-up of 27 and 18months after treatment, respectively.. PLB is a rare malignancy that is difficult to diagnose, particularly in children. Clinicians should increase the awareness of the disease and consider a differential diagnosis of bone lesions. Chemotherapy combined with radiotherapy is a favorable treatment for children with PLB. Early diagnosis and active treatment can improve patient prognosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Magnetic Resonance Imaging; Male; Positron Emission Tomography Computed Tomography; Remission Induction; Thioguanine; Tibia; Vincristine

Topics: Cell Line, Tumor; Coagulants; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Inflammation; Jurkat Cells; Lymphoma, Large B-Cell, Diffuse; Mercaptopurine; Stem Cell Transplantation; Thioguanine; Treatment Outcome

The thiopurines 6-thioguanine (6TG) and 6-mercaptopurine (6MP) are cytotoxic to proliferating cells by a mechanism involving incorporation into DNA via the purine salvage pathway, and resistance to these agents can be conferred by lack of the salvage pathway enzyme hypoxanthine-guanine phosphoribosyltransferase. However, human and murine hypoxanthine-guanine phosphoribosyltransferase-deficient leukemia cell lines have been shown to respond to 6TG by growth arrest and differentiation by a mechanism apparently not involving incorporation of 6TG into DNA. If so, leukemia cells resistant to 6MP should still respond to 6TG by growth arrest via an undescribed epigenetic mechanism. To test this, polyclonal 6MP-resistant variants were produced from three human leukemia cell lines, HL-60, U937, and CCRF-CEM. Treatment of both sensitive and resistant cells with 6TG induced growth arrest. The effect of 6TG in the 6MP-sensitive HL-60 and U937 cells was associated with significant loss of viability and DNA fragmentation. In contrast, the 6TG-treated 6MP-resistant cells exhibited a slower decline in viability and no DNA fragmentation. To identify the mechanism by which 6TG may induce growth arrest, tRNA was isolated from 6MP-resistant cells cultured for 48 h with 6TG. 6TG was found to be incorporated into tRNAs normally containing queuine in the anticodon wobble position. These studies may provide a basis for the development of new therapeutic regimens for the treatment of leukemia.

Topics: Apoptosis; Cell Differentiation; Cell Division; Drug Screening Assays, Antitumor; Humans; Hypoxanthine Phosphoribosyltransferase; Leukemia, Promyelocytic, Acute; Lymphoma, Large B-Cell, Diffuse; Mercaptopurine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; RNA, Transfer; Thioguanine; Tumor Cells, Cultured

Thirty-nine consecutive children (age, 2 to 11 years) with nonlymphoblastic (NL) lymphomas were treated uniformly with chemotherapy based on the LNH-II-85 protocol. The protocol consisted of a remission-induction phase that lasted 30 days and started with cyclophosphamide (CTX) 1.2 g/m2 on day 1, followed by vincristine (VCR) 1.5 mg/m2 on days 3, 10, 17, and 24, daunomycin (DAUNO) 60 mg/m2 on days 12 and 13, and prednisone 40 mg/m2/d for 30 days. If a complete remission was achieved, an intensification regimen was given that consisted of eight courses of teniposide (VM-26) 165 mg/m2 plus cytarabine (ARA-C) 300 mg/m2 every 4 days according to bone marrow tolerance. A continuation phase was subsequently started, with alternating courses of thioguanine (6-TG) 300 mg/m2/d for 4 days plus CTX 1.2 g/m2 on day 5; hydroxyurea 2.5 g/m2/d for 4 days plus DAUNO 45 mg/m2 on day 5; VCR 1.5 mg/m2 plus methotrexate (MTX) 120 mg/m2 (24 hours apart); mercaptopurine (6-MP) 500 mg/m2/d for 4 days plus MTX 40 mg/m2; and VM-26 plus ARA-C for 3 courses (4 days apart), by the end of 48 weeks. CNS prophylaxis consisted of intrathecal administration of MTX, ARA-C, and dexamethasone according to age, administered three times during remission induction and every 6 weeks afterwards.. By the end of the analysis in July 1991, 38 of 39 patients had attained a complete remission and 36 were event-free survivors. Two failures that occurred after completion of therapy were second malignancies (acute lymphocytic leukemia and acute nonlymphocytic leukemia).. These results are significantly better than those obtained with less intensive former regimens performed in our institution before the availability of VM-26. The favorable impact of an intense consolidation phase with VM-26 is remarkably exemplified by three additional patients not included in this study whose families withdrew them from therapy after the intensification phase, all three of whom have been in remission.

Topics: Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Mercaptopurine; Methotrexate; Prednisone; Recurrence; Remission Induction; Survival Rate; Teniposide; Thioguanine; Vincristine