Pediatric ALL Working Party, Korean Society of Hematology, Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
The immunotherapeutic approaches that have been realized in clinical settings have begun a new era in the treatment of acute lymphoblastic leukemia (ALL). Gene-engineered autologous T-cell therapy, called "living drug," has killed leukemic cells and had kept 88% of refractory adult patients with ALL alive in successful molecular remission . We are fully armed with tailored chemotherapy, hematopoietic stem cell transplantation, and gene-engineered T-cell immunotherapy to fight ALL.
Over the past several decades, there have been remarkable advances in childhood ALL. In recent clinical trials, which had better defined risk stratification using minimal residual disease, the 5-year survival rate was more than 85% in developed countries . This improvement is the result of active chemotherapeutic agents being developed, a better understanding of prescribing doses and combining these agents, and the significant progress made in supportive care through multicenter clinical trials. However, we still have to fight a treatment failure of 10-15%. Continued research is required to identify and target specific molecular and genetic abnormalities within leukemic cells as well as to better understand and address individual differences in the pharmacogenetics of chemotherapeutic agents.
Genomic sequencing and adequate analytic platforms, such as gene expression profiling, single-nucleotide polymorphism arrays, and next-generation sequencing, have become available in the treatment of childhood ALL. Molecular biology techniques have revealed many different childhood ALL subtypes that bear features such as iAMP21, CRLF2 rearrangements, IKZF1 alteration, JAK1/2 mutations,
Pharmacogenomics in cancer treatment hold great promise for yielding genetic polymorphisms that could be used to individualize antileukemic agent dosages. Thus far, the only well-established clinical effect refers to mercaptopurine and the genetic polymorphism status of the
Korea has many centers with enhanced resources that can adapt new technologies to clinical practices . However, in Korea, where the national health insurance system controls the application of new laboratory tests or treatments to clinical practice, national health insurance policy limitations hinder the addition of these advances to standard practice guidelines, which would be unlikely in the United States or Europe . In the past, our management guidelines in pediatric ALL have been based mainly on treatment experiences in the United States or Europe, and those guidelines are often different in each institution. However, several years ago, we started multicenter clinical trials for high-risk pediatric ALL patients and have finished patient enrollment. Currently, we are developing new protocols for newly diagnosed high-risk and relapsed ALL patients. In these trials, risk assignment, bone marrow response, and minimal residual disease measurements will be performed on day 7 or day 15 by flow cytometry and reverse transcription PCR (HemaVision).
Because defining the complete genetic repertoire of ALL and the progressive availability of new targeted therapy will make patient subgroups smaller, we will be asked to participate in international collaborative trials. For this to become a reality, we have to keep up with global standards. Now is the time to come together.