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Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration
Ching-Hon Pui1, Jun J Yang2, Stephen P Hunger2
1Ching-Hon Pui, Jun J. Yang, James R. Downing, Williams E. Evans, Mary V. Relling, and Charles G. Mullighan, St Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis, TN; Stephen P. Hunger, University of Colorado School of Medicine and the University of Colorado Cancer Center and Children's Hospital Colorado, Aurora, CO; Rob Pieters, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Martin Schrappe, University Medical Center Schleswig-Holstein, Christian-Albrechts-University, Kiel; Gabriele Escherich, Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany; Andrea Biondi, Clinica Pediatrica and Centro Ricerca Tettamanti, Università di Milano-Bicocca, Monza, Italy; Ajay Vora, Children's Cancer Group, School of Cancer, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom; André Baruchel, Hôpital Robert Debré and University of Paris Diderot, Paris, France; Lewis B. Silverman, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA; Kjeld Schmiegelow, Institute of Clinical Medicine, University of Copenhagen and Juliane Marie Centre, the University Hospital Rigshospitalet, Copenhagen, Denmark; Keizo Horibe, Nagoya Medical Center, Clinical Research Center, Nagoya, Japan; Yves C.M. Benoit, Universiteit Gent, Gent, Belgium; Shai Izraeli, Chaim Sheba Medical Center and Sackler Medical School, Tel Aviv University, Tel Aviv, Israel; Allen Eng Juh Yeoh, Yong Loo Lin School of Medicine and Cancer Science Institute, National University of Singapore, and Viva-University Children's Cancer Centre, National University Hospital, Singapore; and Der-Cherng Liang, Mackay Memorial Hospital, Taipei, Taiwan. ching-hon.pui@stjude.org.
Insights
Collaborative studies have significantly advanced childhood acute lymphoblastic leukemia (ALL) research, leading to improved treatments and survival rates. These efforts enhance personalized therapy and patient quality of life.
Area of Science:
- Pediatric Oncology
- Hematologic Malignancies
- Cancer Genomics
Background:
- Acute lymphoblastic leukemia (ALL) is a significant pediatric cancer.
- Advances in understanding ALL biology and treatment are crucial for improving outcomes.
- Collaborative research initiatives play a vital role in accelerating progress.
Observation:
- International study groups and consortia have been established to conduct collaborative research in childhood ALL.
- High-resolution genome-wide analyses have become integral to ALL research.
- Long-term survival rates for childhood ALL are approaching 90%.
Findings:
- Collaborative studies have refined treatment strategies for specific ALL subtypes, including infant, MLL-rearranged, Philadelphia chromosome-positive, and Philadelphia chromosome-like ALL.
- Recurrent genetic abnormalities responsive to tyrosine kinase inhibitors have been identified.
- Genetic determinants of drug resistance and toxicities have been elucidated, facilitating targeted therapy development.
- Genetic polymorphisms linked to ALL susceptibility and racial/ethnic incidence variations have been recognized.
Implications:
- Collaborative research enhances the understanding of ALL heterogeneity, enabling more personalized treatment approaches.
- Continued collaborative efforts are expected to further improve cure rates and the quality of life for children and adolescents with ALL.
- Translational research from collaborative studies directly impacts clinical practice and patient care.
Purpose:
To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents.
Methods:
A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups.
Results:
With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome-positive, and Philadelphia chromosome-like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL.
Conclusion:
The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL.
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