Annual Meeting Proceedings Part 1 - American Society of Clinical ...

Special Awards
Pediatric Oncology Award and Lecture
Friday, June 1, 2:45 PM
Toward the total cure of childhood acute lymphoblastic leukemia with personalized therapy.
Ching-Hon Pui, MD; St. Jude Children’s Research Hospital and the University of Tennessee Health Science
Center, Memphis, TN
The cure rate of approximately 90% achieved in childhood acute lymphoblastic leukemia (ALL) attests to the
effectiveness of risk-directed therapy developed through well-designed clinical trials and the successful
translation of laboratory discoveries. With optimal systemic and intrathecal therapy, central nervous system
relapse can now be totally prevented without the need of prophylactic cranial irradiation. The results of allogeneic
transplantation have also been improved by more precise HLA matching, killer immunoglobulin-like receptor
genotyping, and better supportive care. Further improvements in treatment outcome and quality of life for these
patients will almost certainly require continued dissection of ALL pathophysiology and the mechanisms of drug
resistance as they relate to the genetic and epigenetic changes for individual patients. The high-risk leukemic cell
genetic abnormalities alone can no longer be considered justification for stem cell transplantation, given the
improved chemotherapy and the substantial heterogeneity among these patients in cooperating mutations,
development stages of the transformed cells, and host pharmacogenetics. Recent advances in global genomic
analyses have identified new recurrent somatic lesions in the leukemic cells that offer not only additional
prognostic information but also the opportunity to apply novel targeted therapy. Notably, the recently identified
mutational spectrum in early T-cell precursor ALL—a subset of ALL with an extremely dire prognosis—
recapitulates that of acute myeloid leukemia, while its global transcriptional profile is similar to that of normal
and myeloid leukemia hematopoietic stem cells, suggesting that additional myeloid-directed therapy might
benefit patients with this leukemia variant. Finally, it may be possible to improve the outcome of “BCR-ABL1like”
ALL, a new subtype of high-risk B-cell precursor ALL with an IZKF1 alteration, by targeting recently
identified activation mutations with tyrosine kinase inhibitors. As the repertoire of targeted therapeutics
including cell- and antibody-based treatment increases, we can look forward to a total cure of ALL with
acceptable toxicity.
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