Infants With ALL

Infant ALL is uncommon, representing approximately 2% to 4% of cases of childhood ALL.[21] Because of their distinctive biological characteristics and their high risk of leukemia recurrence, infants with ALL are treated on protocols specifically designed for this patient population. Common therapeutic themes of the intensive chemotherapy regimens used to treat infants with ALL are the inclusion of postinduction intensification courses with high doses of cytarabine and methotrexate.[22-25]

Infants diagnosed within the first few months of life have a particularly poor outcome. In one study, patients diagnosed within 1 month of birth had a 2-year OS rate of 20%.[26][Level of evidence B4] In another study, the 5-year EFS rate for infants diagnosed at younger than 90 days was 16%.[24][Level of evidence B4]

For infants with KMT2A gene rearrangements, the EFS rates at 4 to 5 years continue to be in the 35% range.[22-24,27,28][Level of evidence B4] Factors predicting poor outcome for infants with KMT2A rearrangements include the following:[23,24]; [29][Level of evidence C2]; [30][Level of evidence B4]

In one report, any CNS involvement at diagnosis (CNS2, CNS3, or traumatic lumbar puncture with blasts) was also found to be an independent predictor of adverse outcome in infants with KMT2A-rearranged ALL.[31]

In addition to having a significantly higher relapse rate than older children with ALL, infant patients more frequently present with a higher acuity. In a large retrospective study, infants with ALL were more likely to present with multisystem organ failure than noninfants (12% and 1%). Infants also had greater requirements for blood products, diuretics, supplemental oxygen, and mechanical ventilation during induction, compared with noninfants.[32]

Infants are also at higher risk of developing treatment-related toxicity, especially infection. With current treatment approaches for this population, treatment-related mortality has been reported to occur in about 10% of infants, a rate that is much higher than the rate in older children with ALL.[23,24] On the COG AALL0631 (NCT00557193) trial, an intensified induction regimen resulted in an induction death rate of 15.4% (4 of 26 patients). The trial was subsequently amended to include a less-intensive induction and enhanced supportive care guidelines, resulting in a significantly lower induction death rate (1.6%; 2 of 123 patients) and significantly higher CR rate (94% vs. 68% with the previous, more intensified induction regimen).[33]