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Life-threatening and fatal infections in children with acute myeloid leukemia: a report from the Children's Oncology Group.

ABSTRACT: To determine among children with acute myeloid leukemia, whether the proportions of life-threatening or fatal infections differed according to the intensity of induction or type of intensification treatment. Participants were children enrolled to the Children's Cancer Group (CCG) 2891 with de novo acute myeloid leukemia. In phase 1 (induction) patients were randomized to 4 cycles of chemotherapy either administered as intensive or standard timing. In phase 2 (intensification), those achieving remission were allocated to allogeneic stem cell transplantation (SCT) if a suitable family donor was available while the remainder were randomized to autologous SCT or chemotherapy. Each infection was classified prospectively as nonlife-threatening, life-threatening, or fatal. The proportion of all infections that were considered life-threatening or fatal was higher with intensive timing compared with standard timing induction (60.3% vs. 37.3%, P<0.0001). Infections caused by Gram-positive and Gram-negative bacteria and fungi were significantly more likely to be severe during intensive compared with standard timing induction. Most molds were life-threatening or fatal. Chemotherapy intensification was not associated with less severe infections compared with SCT. Intensive timing was associated with more severe infections compared with standard timing induction. Prophylactic strategies are likely more important with intensive induction regimens.

SUBMITTER: Sung L

PROVIDER: S-EPMC4490686 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Life-threatening and fatal infections in children with acute myeloid leukemia: a report from the Children's Oncology Group.

Sung Lillian L Buxton Allen A Gamis Alan A Woods William G WG Alonzo Todd A TA

Journal of pediatric hematology/oncology 20120101 1

To determine among children with acute myeloid leukemia, whether the proportions of life-threatening or fatal infections differed according to the intensity of induction or type of intensification treatment. Participants were children enrolled to the Children's Cancer Group (CCG) 2891 with de novo acute myeloid leukemia. In phase 1 (induction) patients were randomized to 4 cycles of chemotherapy either administered as intensive or standard timing. In phase 2 (intensification), those achieving re ...[more]

PMID: 22052170

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Project description:The US Food and Drug Administration recently announced reapproval of gemtuzumab ozogamicin (GO) for treatment of CD33-positive acute myeloid leukemia (AML), thus opening up opportunities to develop strategies for effective use of GO. In light of our recent report showing prognostic significance of CD33 splicing single nucleotide polymorphisms (SNPs), the objective of this study was to comprehensively evaluate CD33 SNPs for accurate prediction of patients with AML who are more or less likely to respond to GO. We investigated the five new CD33 SNPs (rs2455069, rs35112940, rs61736475, rs1803254, and rs201074739) for association with CD33 leukemic cell surface expression and clinical response in pediatric patients with AML enrolled in the Children's Oncology Group AAML0531 trial. We further developed a composite CD33 pharmacogenetics (PGx) score using six CD33 SNPs (CD33_PGx6_score) for association with clinical outcome. Four CD33 SNPs were associated with cell surface CD33 levels and clinical response in the GO versus no-GO arms. Therefore, the CD33_PGx6_score was built using directional genotype scores for the previously reported splicing SNP and five new SNPs. Patients with a CD33_PGx6_score of 0 or higher had higher CD33 expression levels compared with patients with a score of less than 0 (P < .001). In addition, patients with a score of 0 or higher demonstrated an improved disease-free survival in the GO versus no-GO arms (62.5% ± 7.8% v 46.8% ± 8.3%, respectively; P = .008) and a reduced risk of relapse (28.3% ± 7.2% v 49.9% ± 8.4%, respectively; P < .001). No improvement from GO was observed in patients with a CD33-PGx6_score of less than 0. Consistent results were observed across the risk groups. In this study, we report a composite CD33_PGx6_score using directional genotype scores of CD33 SNPs. Once validated, our findings hold promise for use of the CD33_PGx6_score to guide efficient use of GO in patients with AML. In addition, because the CD33_PGx6_score considers SNPs with varying abundance in different ethnic groups, it has potential for global application.

Dataset Information

Life-threatening and fatal infections in children with acute myeloid leukemia: a report from the Children's Oncology Group.

Publications

Life-threatening and fatal infections in children with acute myeloid leukemia: a report from the Children's Oncology Group.

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