High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group study.

Abstract

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.

Clinical significance of central nervous system involvement at diagnosis of pediatric acute myeloid leukemia: a single institution's experience

“…5 In recent years, most pediatric oncology groups have relied increasingly on intrathecal (IT) chemotherapy for the prevention and treatment of CNS leukemia and have reduced the use of CNS irradiation. 6 In addition, new antileukemic therapies (eg, high-dose cytarabine 11 and cladribine 12 ) offer increased CNS penetration. We analyzed the clinical features and outcome of pediatric patients with and without CNS involvement in a cohort of 290 patients treated on four institutional AML protocols.…”

“…Further, there is little information about the appropriate threshold (white blood cell (WBC) count in cytocentrifuged CSF) needed to diagnose CNS involvement in AML. The threshold used by an Italian research group, 4 The Pediatric Oncology Group (POG), 6 and St Jude 7 is the presence of any blast cells (regardless of cell count). The Children's Cancer Group (CCG) 8 and the Berlin-Frankfurt-Münster (BFM) group 3 use a threshold of 5 and 10 WBC/ml, respectively.…”

Prognostic factors in infants with acute myeloid leukemia

“…Some studies have shown an unfavorable outcome in very young patients, 18,22 others have found comparable survival rates between the two age groups, 17,21,[23][24][25][26] while still others indicated a better prognosis for infants. 19 are very few data on the blast cell genetics of infants with AML. Only four studies have attempted to assess the prognostic significance of MLL/11q23 rearrangements, the most common genetic lesion in infants with AML.…”

“…Many studies combined infants less than 12 months of age with those 1-2 years old in a single group. [17][18][19][20][21][22] Second, the prognosis of AML in very young patients as compared to older patients varied among different clinical protocols, underscoring the overriding importance of treatment efficacy. Some studies have shown an unfavorable outcome in very young patients, 18,22 others have found comparable survival rates between the two age groups, 17,21,[23][24][25][26] while still others indicated a better prognosis for infants.…”

Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report

“…Other changes were introduced in the treatment regimen: the consolidation course of EORTC 58872, comprising four fortnightly doses of MTZ and which had induced very severe and prolonged neutropenia, was deleted and a combination of highdose Ara-C and the anthracycline to which the patient had been randomized was substituted for it. 11,12 The second intensification was the 'DCTER' course according to the CCG 2861 protocol. 4,5 The third intensification remained identical to the second intensification of 58872.…”