Response to remission induction chemotherapy

More than 95% of children with newly diagnosed ALL will achieve a CR within the first 4 weeks of treatment. Of those who fail to achieve CR within the first 4 weeks, approximately one-half will experience a toxic death during the induction phase (usually caused by infection) and the other half will have resistant disease (persistent morphological leukemia).[34-36]; [37][Level of evidence C1]

Remission is classically defined as an end-induction bone marrow examination by routine microscopic cytomorphology with fewer than 5% lymphoblasts at the end of induction (M1). The Ponte de Legno consortium includes approximately 15 large national and international cooperative groups devoted to the study and treatment of childhood ALL. This group published a consensus definition of complete remission, as follows:[38]

Most patients with persistence of morphologically detectable leukemia at the end of the 4-week induction phase have a poor prognosis and may benefit from an allogeneic hematopoietic stem cell transplant (HSCT) once CR is achieved.[4,39,40] In a retrospective study of 1,041 patients with persistent disease after induction therapy (induction failure) who were treated between 1985 and 2000, the 10-year OS rate was 32%.[41] A trend for superior outcome with allogeneic HSCT compared with chemotherapy alone was observed in patients with T-cell phenotype (any age) and B-ALL patients older than 6 years. B-ALL patients who were aged 1 to 5 years at diagnosis and did not have any adverse cytogenetic abnormalities (KMT2A rearrangement, BCR::ABL1) had a relatively favorable prognosis, without any advantage in outcome with the utilization of HSCT compared with chemotherapy alone.[41]

A follow-up retrospective study reported the outcomes of 325 children and adolescents with T-ALL and initial induction failure who were treated between 2000 and 2018.[42] The 10-year OS rate was 54.7%, which was significantly better than the rates of patients in historical cohorts who were treated between 1985 and 2000 (10-year OS rate, 27.6%). Complete remission was eventually achieved in 93% of patients with T-ALL and initial induction failure. Of the patients who achieved complete remission, 72% underwent HSCT. Adjusting for time to transplant, the 10-year OS rate was 66.2% for these patients, compared with 50.8% for those who did not undergo transplants.

The incorporation of nelarabine may be of value for patients with T-ALL and have induction failure. The COG AALL0434 (NCT00408005) study included 43 patients with more than 25% blasts in an end-induction bone marrow aspirate. Of these patients, 23 patients were nonrandomly assigned to therapy that included high-dose methotrexate and nelarabine as part of a multidrug regimen, and 20 patients underwent allogeneic transplant. The 5-year EFS rate was 53.1% (± 9.4%) for the patients who received high-dose methotrexate and nelarabine. There was no difference in outcome for these two groups (HR, 0.66; 95% CI, 0.24–1.83; P = .423).[43]

For patients who achieve CR, measures of the rapidity of blast clearance and MRD determinations have important prognostic significance, particularly the following:

For more information, see the Response to initial treatment section.

For specific information about CNS therapy to prevent CNS relapse in children with newly diagnosed ALL, see the CNS-Directed Therapy for Childhood ALL section.