Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia

Abstract

Contemporary paediatric clinical trials have improved 5-year event-free survival above 85% and 5-year overall survival above 90% in B-cell acute lymphoblastic leukaemia (ALL) in many study groups, whilst outcomes for T-cell ALL are still lagging behind by 5-10% in most studies. Several factors have contributed to this discrepant outcome. First, patients with T-cell ALL are generally older than those with B-cell ALL and, therefore, have poorer tolerance to chemotherapy, especially dexamethasone and asparaginase, and have increased risk of extramedullary relapse. Second, a higher proportion of patients with B-cell ALL have favourable genetic subtypes (eg, ETV6-RUNX1 and high hyperdiploidy), which confer a superior outcome compared with favourable subtypes of T-cell ALL. Third, T-cell ALL blasts are generally more resistant to conventional chemotherapeutic drugs than are B-cell ALL blasts. Finally, patients with B-cell ALL are more amendable to available targeted therapies, such as Philadelphia chromosome-positive and some Philadelphia chromosome-like ALL cases to ABL-class tyrosine kinase inhibitors, and CD19-positive and CD22-postive B-cell ALL cases to a variety of immunotherapies. Several novel treatments under investigation might narrow the gap in survival between T-cell ALL and B-cell ALL, although novel treatment options for T-cell ALL are limited.

Figure:. Estimated frequencies of specific genetic subtypes of childhood ALL

Pie charts represent patients with B-cell ALL treated in the St Jude Total Therapy study XV with modifications to account for discoveries of novel genetic abnormalities (A), and patients with T-cell ALL who were studied as part of the Therapeutically Applicable Research to Generate Effective Treatments initiative and treated in Children’s Oncology Group studies (B). T-cell ALL cases were divided according to dysregulation of targetable functional pathways (outer ring). Subtypes are grouped into low-risk, intermediate-risk, and high-risk categories on the basis of 5-year survival rates: over 90%, 70–90%, and less than 70% in B-cell ALL (overall survival) and T-cell ALL (event-free survival). The outcome (event-free survival) for patients treated in the AALL0434 trial, used for the T-cell ALL risk grouping in this figure, is superior to that in most other published studies. ALL=acute lymphoblastic leukaemia.