Outcome of Adolescent and Young Adults with Acute Myeloid Leukemia Treated with Pediatric Protocols: A Report from the 3 Japanese Cooperative Studies

BACKGROUND: There have been conflicting results from several large pediatric AML collaborative groups comparing survival of adolescent and young adults (AYAs) to that of younger patients with AML. We conducted a retrospective analysis using data from 3 Japanese pediatric AML studies; AML99 (2000-02), AML9805 (1998-2002), and AML-05 (2006-10), conducted by the Japanese Childhood AML Cooperative Study (consisted of Tokyo Children’s Cancer Study Group (TCCSG), Japan Association of Childhood Leukemia Study (JACLS), and Kyushu Yamaguchi Children’s Cancer Study Group (KYCCSG)), the Japanese Childhood Cancer and Leukemia Study Group (CCLSG), and the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG, the first Japanese national study group), respectively.

PATIENTS & METHODS: Among the 782 patients with de novo AML (excluding acute promyelocytic leukemia and Down syndrome), 44 were AYAs (age ≥15 years), 574 were age 2 to 14 years, and 164 were infants (age <2 years) at diagnosis. Because of the underlying differences in biological characteristics, further analysis on event-free survival (EFS), overall survival (OS), cumulative incidence of relapse (RR) and treatment-related mortality (TRM) were compared between AYAs and patients 2 to 14 years old.

RESULTS: 29.5% (13/44) of AYAs were t(8;21) (vs. 37.1% of 2 to 14 years old, P=0.315), 38.6% (17/44) were normal karyotype (vs. 22.0%, P=0.011), and 16.2% of the tested cases (6/37) were FLT3-ITD positive (vs. 9.4%, P=0.554). Complete remission (CR) rate after 2 induction courses was similar between AYAs and patients 2 to 14 years old: 88.6% vs. 88.8% (P=0.965). Five-year EFS rate was also similar between the two cohorts: 55.2% vs. 59.2% (P=0.578). However, 5-year OS rate was significantly poorer in AYAs: 54.7% vs 73.8% (P=0.005). Total 19 events were observed among the 44 AYA patients; 4 failures to achieve CR, 12 relapses, and 3 deaths. Fourteen out of the 16 patients with non-CR or relapse eventually died and 8 deaths were treatment-related. In fact, 5-year RR was similar between the 2 age groups (32.7% vs. 30.1%, P=0.819), but TRM was significantly higher in AYAs (33.2% vs. 12.4%, P=0.001). In multivariate analysis, using Cox proportional hazard regression model, age ≥15 years old at diagnosis, absence of low risk cytogenetics (t(8;21) or inv(16)), and no remission after initial induction course were associated with both poorer OS and higher TRM, while high white cell count at diagnosis (≥ 100,000/μL) and presence of high risk cytogenetics (-7, 5q-, t(16;21)(p11:q22)/FUS-ERG, Philadelphia chromosome, and/or FLT3-ITD) were not siginificant.

CONCLUSIONS: AYAs with AML had inferior OS, but not EFS, due to higher incidence of TRM especially after failure of initial treatment.