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Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3)
ZoAnn E Dreyer1, Joanne M Hilden, Tamekia L Jones
1Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.
Insights
Infants with acute lymphoblastic leukemia (ALL) treated with shortened, intensified therapy had a 5-year event-free survival (EFS) of 42.3%. Younger infants (≤90 days) and those with MLL-rearranged ALL had poorer outcomes, highlighting critical prognostic factors.
Area of Science:
- Pediatric Oncology
- Hematologic Malignancies
- Leukemia Research
Background:
- Infants with acute lymphoblastic leukemia (ALL) exhibit aggressive disease and poor prognosis, with high rates of early relapse.
- Approximately 75% of infant ALL cases involve MLL-rearranged (MLL-R) ALL, characterized by low event-free survival (EFS) rates of 20-30%.
Purpose of the Study:
- To evaluate the efficacy of a shortened (46-week), intensified therapy regimen (Children's Oncology Group P9407) in infants with ALL.
- To identify prognostic factors influencing treatment outcomes in this vulnerable patient population.
Main Methods:
- The Children's Oncology Group P9407 trial involved three cohorts due to modifications for induction toxicity.
- The third cohort included 147 infants diagnosed with acute lymphoblastic leukemia.
Main Results:
- The overall 5-year event-free survival (EFS) and overall survival (OS) were 42.3% and 52.9%, respectively.
- Infants diagnosed at ≤90 days of age had a significantly lower 5-year EFS (15.5%) compared to those diagnosed >90 days (48.5%).
- MLL-rearranged ALL showed a lower 5-year EFS (43.8%) compared to MLL-germline ALL (69.1%) in infants >90 days old.
Conclusions:
- Age ≤90 days at diagnosis emerged as the most critical prognostic factor for infant ALL.
- Despite intensified and shortened therapy, event-free survival remained suboptimal for MLL-rearranged ALL, indicating a need for further treatment advancements.
Background:
Infants with acute lymphoblastic leukemia (ALL) present with aggressive disease and a poor prognosis. Early relapse within 6-9 months of diagnosis is common. Approximately 75% of infants have MLL-rearranged (MLL-R) ALL with event free survival (EFS) ranging from 20% to 30%. Children's Oncology Group (COG) P9407 used shortened (46 weeks), intensified therapy to address early relapse and poor EFS.
Procedure:
P9407 therapy was modified three times for induction toxicity resulting in three cohorts of therapy. One hundred forty-seven infants were enrolled in the third cohort.
Results:
We report an overall 5-year EFS and OS of 42.3 ± 6% and 52.9 ± 6.5% respectively. Poor prognostic factors included age ≤90 days at diagnosis, MLL-R ALL and white cell count ≥50,000/μl. For infants ≤90 days of age, the 5-year EFS was 15.5 ± 10.1% and 48.5 ± 6.7% for those >90 days (P < 0.0001). Among infants >90 days of age, 5-year EFS rates were 43.8 ± 8% for MLL-R versus 69.1 ± 13.6% for MLL-germline ALL (P < 0.0001).
Conclusions:
Age ≤90 days at diagnosis was the most important prognostic factor. Despite shortened therapy with early intensification, EFS remained less than 50% overall in MLL-R ALL.
