Decreased relapsed rate and treatment-related mortality contribute to improved outcomes for pediatric acute myeloid leukemia in successive clinical trials

Abstract

Background: Outcomes for children with acute myeloid leukemia (AML) have improved over the past 20 years even though the medications used for induction therapy have not changed.

Methods: This study analyzed data from patients with AML who were enrolled in successive protocols (AML97 and AML02) to determine the contributors to the improved outcomes of the latter clinical trial.

Results: There were significant improvements in 5-year overall survival (48.9% vs 71.2%; P < .0001) and event-free survival (43.5% vs 61.8%; P = .002) from AML97 to AML02. The 5-year cumulative incidence of early death (ED)/treatment-related mortality (TRM) was reduced for patients treated in AML02 (18.5% vs 7.9%; P = .007). Although the overall incidence of refractory disease (6.5% vs 5.6%; P = .736) and relapse (29.3% vs 21.0%; P = .12) did not differ between the 2 studies, patients with low-risk AML who were treated in AML02 had a reduced incidence of relapse (27.3% vs 8.8%; P = .036).

Conclusions: The improved outcomes of the AML02 trial resulted from improved disease control for low-risk patients and overall decreased ED/TRM. These results emphasize the importance of supportive-care measures throughout chemotherapy courses and hematopoietic cell transplantation and the value of treatment intensity for patients with low-risk AML while underscoring the need for novel therapy, rather than increased therapy intensity, for children with high-risk AML. Cancer 2017;123:3791-3798. © 2017 American Cancer Society.

Keywords: leukemia; outcomes; pediatric; supportive care.

Figure 1

(a) Overall and event free survival and AML97 and AML02. (b) Event free survival of AML97 and (c) AML02 showing the relative contribution of first events to the failure rate. First events shown are ED/TRM (early death / treatment related mortality), relapsed disease, refractory disease, and other events (withdrawal or secondary malignancy).

Figure 1

(a) Overall and event free survival and AML97 and AML02. (b) Event free survival of AML97 and (c) AML02 showing the relative contribution of first events to the failure rate. First events shown are ED/TRM (early death / treatment related mortality), relapsed disease, refractory disease, and other events (withdrawal or secondary malignancy).

Figure 1

(a) Overall and event free survival and AML97 and AML02. (b) Event free survival of AML97 and (c) AML02 showing the relative contribution of first events to the failure rate. First events shown are ED/TRM (early death / treatment related mortality), relapsed disease, refractory disease, and other events (withdrawal or secondary malignancy).

Figure 2

Cumulative incidence of (a) ED/TRM as first event for all patients on AML97 and AML02, (b) TRM as first event for patient in receiving chemotherapy or autologous HCT and (c) TRM as first event for patients receiving allogeneic HCT.

Figure 2

Cumulative incidence of (a) ED/TRM as first event for all patients on AML97 and AML02, (b) TRM as first event for patient in receiving chemotherapy or autologous HCT and (c) TRM as first event for patients receiving allogeneic HCT.

Figure 2

Cumulative incidence of (a) ED/TRM as first event for all patients on AML97 and AML02, (b) TRM as first event for patient in receiving chemotherapy or autologous HCT and (c) TRM as first event for patients receiving allogeneic HCT.

Figure 3

Cumulative incidence of relapsed disease for patients AML97 and AML02, based upon initial risk classification as (a) low risk, (b) standard risk, and (c) high risk.

Figure 3

Cumulative incidence of relapsed disease for patients AML97 and AML02, based upon initial risk classification as (a) low risk, (b) standard risk, and (c) high risk.

Figure 3

Cumulative incidence of relapsed disease for patients AML97 and AML02, based upon initial risk classification as (a) low risk, (b) standard risk, and (c) high risk.

Figure 4

Overall Survival for patients with relapsed or refractory AML according to frontline treatment protocol.

Figure 5

Cumulative dosing of chemotherapy received during the two standard induction courses on AML97 and AML02. Patients on AML02 were randomized between high (hatched bar) and low dose cytarabine (black bar) during the first induction course.