Blood Cancer J: two-dose versus three-agent induction chemotherapy for pediatric acute myeloid leukemia: a randomized controlled trial

Acute myeloid leukemia (AML) is rare in children compared to older adults.

Over the past few decades, there has been a significant improvement

in the survival rate of AML in children in high-income countries (HICs).

This improvement was achieved through better risk stratification, improved supportive care, and allogeneic hematopoietic stem cell transplantation (HSCT).

However, the benefits of three-drug induction chemotherapy over two-agent induction chemotherapy have not been evaluated in pediatric acute myeloid leukemia (AML).

Therefore, a research team conducted a randomized controlled trial to determine the benefits of the three-drug induction regimen.

Patients aged 1 to 18 years newly diagnosed with AML were randomized to receive two cycles of daunorubicin and ara-C (DA) induction chemotherapy or two cycles of ara-C, daunorubicin, and etoposide (ADE).

After induction, both groups of patients received two cycles of high-dose ara-C consolidation therapy

.

The primary objective of the study was to compare event-free survival (EFS) between the

two groups.

Secondary objectives include comparing compound complete response (cCR) rates, overall survival (OS), and toxicity

.

The study randomized 149 patients, of whom 77 were in the DA group and 72 in the ADE group

.

The median age was 8.7 years, with 92 (62%) patients being male

.

The median follow-up was 50.9 months

.
The cCR rates in the DA and ADE groups after the second induction were 82% and 79%, respectively (p = 0.68).

There were 13 (17%) induced death in the DA group and 12 (17%) in the ADE group (p = 0.97).

 

Pictured: Kaplan-Meier survival curve
.
Event-free survival (EFS) (p=0.66) was compared between daunorubicin and ARAC(DA) and ARAC(DA) and Etoposide (ADE) groups, and overall survival (OS) (p=0.74) was compared between DA and ADE groups.

 

Table: Comparison of grade 3-5 toxicity between two groups of researchers

The 5-year EFS for the DA and ADE groups is 34.4% and 34.5% (p = 0.66),
respectively.
The 5-year OS for DA and ADE groups is 41.4% and 42.09% (p = 0.74),
respectively.
There were no significant differences in toxicity between regimens
.

Overall, there were no statistically significant differences in EFS, OS, CR, or toxicity between ADE and DA regimens
in the study.
Randomised controlled trials are also needed in the future to look for the optimal number and duration
of induction chemotherapy drugs in children with AML.

 

Original source:

Radhakrishnan V, Bakhshi S, Kayal S, Thampy C, Batra A, Shenoy PK, Kumar H, Rajaraman S, Chaudhary S, Bisht R, Dubashi B, Ganesan TS.
Two-drug versus three-drug induction chemotherapy in pediatric acute myeloid leukemia: a randomized controlled trial.
Blood Cancer J.2022 Sep 6; 12(9):131.doi: 10.1038/s41408-022-00726-1.PMID: 36068213.