Prognostic factors in children and adolescents with acute myeloid leukemia (excluding children with Down syndrome and acute promyelocytic leukemia): univariate and recursive partitioning analysis of patients treated on Pediatric Oncology Group (POG) Study 8821

Abstract

The purpose of the paper was to define clinical or biological features associated with the risk for treatment failure for children with acute myeloid leukemia. Data from 560 children and adolescents with newly diagnosed acute myeloid leukemia who entered the Pediatric Oncology Group Study 8821 from June 1988 to March 1993 were analyzed by univariate and recursive partitioning methods. Children with Down syndrome or acute promyelocytic leukemia were excluded from the study. Factors examined included age, number of leukocytes, sex, FAB morphologic subtype, cytogenetic findings, and extramedullary disease at the time of diagnosis. The overall event-free survival (EFS) rate at 4 years was 32.7% (s.e. = 2.2%). Age у2 years, fewer than 50 × 10 9 /l leukocytes, and t(8;21) or inv(16), and normal chromosomes were associated with higher rates of EFS (P value = 0.003, 0.049, 0.0003, 0.031, respectively), whereas the M5 subtype of AML (P value = 0.0003) and chromosome abnormalities other than t(8;21) and inv(16) were associated with lower rates of EFS (P value = 0.0001). Recursive partitioning analysis defined three groups of patients with widely varied prognoses: female patients with t(8;21), inv(16), or a normal karyotype (n = 89) had the best prognosis (4-year EFS = 55.1%, s.e. = 5.7%); male patients with t(8;21), inv(16) or normal chromosomes (n = 106) had an intermediate prognosis (4-year EFS = 38.1%, s.e. = 5.3%); patients with chromosome abnormalities other than t(8;21) and inv(16) (n = 233) had the worst prognosis (4-year EFS = 27.0%, s.e. = 3.2%). One hundred and thirty-two patients (24%) could not be grouped because of missing cytogenetic data, mainly due to inadequate marrow samples. The results suggest that pediatric patients with acute myeloid leukemia can be categorized into three potential risk groups for prognosis and that differences in sex and chromosomal abnormalities are associated with differences in estimates of EFS. These results are tentative and must be confirmed by a large prospective clinical trial.

Childhood acute myeloid leukemia with CBFβ‐MYH11 rearrangement: Study of incidence, morphology, cytogenetics, and clinical outcomes of Chinese in Hong Kong

“…These 5 patients showed better clinical outcomes than did the other 37 patients with childhood AML with known follow-up information in terms of overall (100% vs. 64%) and diseasefree (75% vs. 61%) survivals at 3.5 years and relapse rates (20% vs. 34%), although statistical significance was not reached. The favorable clinical outcomes are consistent with observations in adult and pediatric AML cases with inv(16)(p13q22) [2]. Infantile AML usually shows a poor prognosis and is rarely associated with inv(16)(p13q22), which is an indicator of good prognosis.…”

“…This AML subgroup generally has a better prognosis both in adult [1] and pediatric patients [2]. At the molecular level, the inv(16)(p13q22) results in the fusion of the core binding factor b (CBF ) gene at 16q22 to the smooth muscle myosin heavy chain (MYH11) gene at 16p13.…”

Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia

“…2,3,21 In childhood AML, some prognostic factors have been analyzed. [22][23][24][25] There are some reports of drug sensitivity testing with the MTT assay in childhood ALL, and drug sensitivity has been reported to provide prognostic information. [6][7][8][9][10][11] Thus far, however, only a few studies have sought correlations between in vitro drug resistance and clinical outcome in childhood AML.…”

High Bad and Bax mRNA expression correlate with negative outcome in acute myeloid leukemia (AML)

“…A trend towards unfavorable prognosis was found for relapsed and secondary AML compared to de novo AML (P = 0.097) and for unfavorable karyotypes compared with standard or favorable karyotypes (P = 0.186) confirming earlier data from the literature. 33,34 There Table 4 Gene expression and relative risk (RR) of tumor-related death…”