Contemporary treatments have resulted in 5-year event-free survival rates (EFS) of approximately 75% to 80% for childhood
acute lymphoblastic leukemia (ALL). Relapses of ALL in children were more often in HR-ALL but also in very few non-HR-ALL. Thus current clinical study of ALL has focused on improving the outcome of a few subtypes of HR-ALL. Infants with ALL have a particularly high risk of treatment failure. Infant ALL Interfant-99 study found that MLL rearrangement, age younger than 6 months, poor response to a
prednisone prophase and high WBC count were strong independent predictive factors for poor prognosis in infants with ALL. Treatments with hybrid protocol, including both lymphoid- and myeloid-directed treatment elements, also contain HD-MTX and high dose
Ara-C(HD-
Ara-C), will further improve the outcome for infant ALL. Children
Philadelphia chromosome positive ALL (Ph+ALL) was associated with a high relapse rate when treated with
chemotherapy alone. The Children's Oncology Group (COG) AALL0031 trial showed that the addition of
tyrosine kinase inhibitors(TKIs)
imatinib to intensive
chemotherapy resulted in 3-year EFS more than historical control treated with
chemotherapy alone. These findings create a new paradigm for integrating molecularly targeted agents with intensified
chemotherapy. Children with
T-ALL have had a worse outcome than with the precursor B-cell ALL previously. With more intensified
chemotherapy , outcomes for children
T-ALL were improved, approaching those for the precursor B-cell ALL. Recently, COG decided to treat children with T-cell ALL with separate protocols different from those for the precursor B-cell ALL, and the protocols of BFM for children with
T-ALL have been the same as those of the precursor B-cell ALL. Early precursor T-cell ALL, a novel subtype of T-cell ALL, was identified by gene expression profiling, flow cytometry, and single nucleotide polymorphism array analyses. ETP-ALL, identified in 13% of T-cell ALL cases, is characterized by a distinctive immunophenotype (CD1a and CD8 negativity, with weak expression of CD5 and co-expression of stem cell or myeloid markers). A retrospective analysis suggested that ETP-ALL had a poor prognosis. The advent of high-resolution genome-wide analyses has provided new insights into leukemogenesis and identified many novel subtypes of
leukemia. Ph-like ALL (BCR-ABL1-like ALL) patients lack a previously identified chromosomal rearrangement, but exhibit a gene-expression profile highly similar to that of Ph+ALL, and often have deletion/mutation of IKZF1, CRLF2 rearrangments and JAK1/2sequence mutations which are also common in Ph+ALL. The prognosis of Ph-like ALL is poor. Development of new agents targeted to leukemogenic pathways will promise to further improve the outcome of children ALL.