Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration

Abstract

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.

Osteonecrosis in children with acute lymphoblastic leukemia

“…Marina Kunstreich, 1 Sebastian Kummer, 2 Hans-Juergen Laws, 1 Arndt Borkhardt, 1 and Michaela Kuhlen 1…”

“…Currently, more than 90% of children and adolescents can be cured and become long-term survivors. 1,2 Thus, the long-term adverse effects of treatment become increasingly important. Osteonecrosis is one of the most common and debilitating therapy-related side effects of anti-leukemic treatment and can adversely affect long-term quality of life.…”

Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia

“…[1][2][3][4] However, because only a minority of pediatric patients have known targetable lesions, novel and broadly active agents are urgently needed. Selinexor (KPT-330), a selective inhibitor of exportin 1 (XPO1), may represent such an agent.…”

Perspectives of Fc engineered antibodies in CD19 targeting immunotherapies in pediatric B-cell precursor acute lymphoblastic leukemia

“…Although about 90% of children can be cured by chemotherapy alone, 10 Fc engineered CD19 antibodies may provide an additional tool with limited side effects for some patients. 8 , 9 We have recently evaluated the efficacy of Fc engineered CD19 antibodies in xenograft models of pediatric BCP-ALL, 11 the most common malignancy in childhood.…”