Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.107 (DAT)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From 1982 to 1990, 340 children with newly diagnosed ANLL entered two consecutive AIEOP trials: LAM 8204 (1982-1987) and LAM 87 (1987-1990). Patients in both studies received identical remission induction with Daunorubicin and ARA-C. In the first study (LAM 8204) 167/171 patients were consolidated with four courses of DAT, followed by six additional courses of continuation therapy with three drug pairs given sequentially. Periodic intra-thecal ARA-C was used for CNS prophylaxis. For patients remaining on protocol, the OFS and EFS probability at 8 years was 35% and 30%, respectively. Induction response and EFS were adversely predicted by FAB MS subtype and hyperleukocytosis. In LAM 8204 trial there were 30 withdrawals represented by patients undergoing allogeneic (14) or autologous (16) BMT. For these patients the DFS probability at 5 years was 64% and 50%, respectively. On LAM-87 trial, 136/169 patients were evaluable and 98 (76%) attained CR. After consolidation with one course of DAT, patients with an HLA-identical donor underwent allogeneic BMT and those lacking a matched donor were randomized to receive either autologous BMT or the LAM 8204 postremission chemotherapy. The 2-year probability of DFS for allografted patients was 76% significantly higher (P = 0.0001) than that observed for patients on chemotherapy (12%) or autologous BMT (31%) arms.
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PMID:Allogeneic vs autologous BMT vs intensive chemotherapy in childhood AnLL during first complete remission: AIEOP experience. AIEOP Cooperative Group. 185 93

In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4) followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85% [SE = 2%] in each group), induction deaths (6.5% v 7.0%), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34% [SE = 11%] v 29% [SE = 4%]), and disease-free survival (DFS at 3 years, 42% [SE = 14%] v 34% [SE = 4%]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/microL had significantly better outcome (EFS of 55% [SE = 10%] and 36% [SE = 5%] at 3 years, respectively) than children greater than or equal to 2 years and those with WBCs greater than or equal to 100,000/microL (EFS of 27% [SE = 5%] and 20% [SE = 9%] at 3 years, respectively.
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PMID:High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group study. 206 54