Outcomes of adolescent and young adult patients with AML treated on adult versus pediatric protocols

Abstract

Abstract Background: Acute Myeloid Leukemia (AML) treatment in adolescent and young adult (AYA) patients (pts) may be challenging due to the choice between adult and pediatric regimens. Pediatric protocols have higher cumulative doses of chemotherapy given in two induction cycles, while adult regimens are tailored towards tolerability and are extrapolated from those designed for older pts. Ultimately, regimen choice may impact outcomes as exemplified in B-cell acute lymphoblastic leukemia (B-ALL), where the use of modified pediatric regimens is now the standard of care for AYA pts after having shown to improve overall survival. Yet, outcomes of pediatric versus (vs) adult treatment paradigms for other hematologic malignancies, such as AML, remain unknown. To address this question, we performed a single-center retrospective study examining the outcomes of AYA pts treated with pediatric vs adult AML induction regimens. Methods: Pts aged 15-39 years at Johns Hopkins Hospital (JHH) who had an eligible AML induction therapy plan between January 1, 2016, and December 31, 2024, were reviewed. Pt demographics, disease characteristics, induction therapy regimen, clinical characteristics during treatment, bone marrow transplant (BMT) referrals, and outcomes were reviewed as of the data cutoff of June 30, 2025. Results: We identified 138 pts (age 15-39 years) treated with an AML induction therapy plan with 121 pts receiving adult-based and 17 receiving pediatric-based regimens. The median age of those treated on an adult regimen was 32 years (range 19-39) and on a pediatric regimen was 20 years (range 16-24) (p<0.001). 94% (n=16) of pts treated via pediatric paradigms received two induction cycles, whereas only those with refractory disease were treated with an alternate induction regimen in the adult cohort (16.5%, n=20) (p< 0.001). Disease characteristics were similar in adult vs pediatric treatment cohorts: 22.3% (n=27) vs 23.5% (n=4) harboring KMT2A-rearrangements, MECOM-rearrangements, or complex karyotypes; 23.1% (n=28) vs 23.5% (n=4) having low risk disease with either core binding factor translocations or bi-allelic CEBPA mutations; 24% (n=29) and 11.8% (n=2) having FLT3 internal tandem duplications or tyrosine kinase domain mutations. 69% (n=84) of those on adult-like regimens received a “7+3” backbone containing 100 mg/m2 cytarabine continuously for seven days (cumulative dose 700 mg/m2) and 12 mg/m2 daily of idarubicin for three days (cumulative dose 36 mg/m2). 70% (n=12) of those on pediatric-like regimens received a “10 and 3” backbone containing cytarabine 100 mg/m2/dose twice daily for 10 days, and daunorubicin 50 mg/m2 daily for three days for induction I of which 83% (10/12) received induction II with an additional eight days of cytarabine (cumulative dose 3800 mg/m2) and three days of daunorubicin (cumulative dose 300 mg/m2). Etoposide was given to 11% (n=13) adult regimens and 41% (n=7) pediatric regimens (p=0.0036), and gemtuzumab ozogamicin was given in 15.7% (n=19) adult and 52.9% (n=9) pediatric regimens (p=0.0013). At diagnosis, 12% (n=15) and 6% (n=1) of adult vs pediatric treated pts were enrolled in clinical trials (p=0.69). 92% (n=110) and 65% (n=11) pts in the adult vs pediatric cohorts were referred for bone marrow transplantation (p=0.0054). 55% (n=72) pts in the adult cohort and 76% (n=13) on the pediatric cohort had de novo AML and were treated for their first induction at JHH. Finally, of pts with de novo AML who received their initial induction at JHH, the median overall survival was not reached and survival at three years was 66.8% (95% CI 55.4%-80.6%) and 62.5% (95% CI 38.9%-100%), for pts treated via adult vs pediatric regimens, respectively (p=0.72).Conclusion: At our single center, more AYA pts with AML are treated via an adult treatment plan even though many may be eligible for COG studies. Unlike in B-ALL, overall survival does not seem to be affected by treatment paradigms, even with a significant age difference between cohorts. The factors determining whether AYA pts are treated on an adult or pediatric protocol remain unclear, raising questions of whether these decisions are influenced by differences in referral networks or if pt choice may play a role. A multicenter retrospective study is underway to confirm these data; however, ultimately a prospective trial will be needed to definitively help oncologists optimize treatment regimens to provide the best care for AYA pts with AML.