Persistent leukemia at the EOI (induction failure)

Nearly all children with ALL achieve complete morphological remission by the end of the first month of treatment. The presence of greater than 5% lymphoblasts by morphological assessment at the EOI phase is observed in 1% to 2% of children with ALL.[22,23,151-153]

Features associated with a higher risk of induction failure include the following:[153-155]

In a large retrospective study, the OS rate of patients with induction failure was only 32%.[151] However, there was significant clinical and biological heterogeneity. A relatively favorable outcome was observed in patients with B-ALL between the ages of 1 and 5 years without adverse cytogenetics (KMT2A rearrangement or BCR::ABL1). This group had a 10-year survival rate exceeding 50%, and hematopoietic stem cell transplant (HSCT) in first remission was not associated with a survival advantage compared with chemotherapy alone for this subset. Patients with the poorest outcomes (10-year survival rate, <20%) included those who were aged 14 to 18 years, or who had the BCR::ABL1 fusion or KMT2A rearrangement. B-ALL patients younger than 6 years and T-ALL patients (regardless of age) appeared to have better outcomes if treated with allogeneic HSCT after achieving CR than those who received further treatment with chemotherapy alone.[151] However, in the COG AALL0434 (NCT00408005) study, an advantage for HSCT in first CR for T-ALL patients with induction failure (defined as M3 marrow at EOI) was not observed. In this study, T-ALL patients were assigned to receive nelarabine during several postinduction treatment phases and high-dose methotrexate during the first interim maintenance phase. The 5-year EFS rate of these patients was 53.1%, with no significant difference between those who proceeded to HSCT in first CR (n = 20) and those who did not (n = 23) (P = .42).[158]