Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers

Research output: Contribution to journalJournal articleResearchpeer-review

Stine N. Nielsen, Frank Eriksson, Susanne Rosthoej, Mette K. Andersen, Erik Forestier, Henrik Hasle, Lisa L. Hjalgrim, Ann Aasberg, Jonas Abrahamsson, Mats Heyman, Ólafur G. Jónsson, Kaie Pruunsild, Goda E. Vaitkeviciené, Kim Vettenranta, Kjeld Schmiegelow

BACKGROUND: The improved survival rates for childhood acute lymphoblastic leukemia (ALL) may be jeopardized by the development of a second cancer, which has been associated with thiopurine therapy.

PROCEDURE: We retrospectively analyzed three sequential Nordic Society of Paediatric Haematology and Oncology's protocols characterized by increasing intensity of thiopurine-based maintenance therapy. We explored the risk of second cancer in relation to protocols, risk group, thiopurine methyltransferase (TPMT) activity, ALL high hyperdiploidy (HeH), and t(12;21)[ETV6/RUNX1].

RESULTS: After median 9.5 years (interquartile range, 5.4-15.3 yrs) of follow-up, 40 of 3,591 patients had developed a second cancer, of whom 38 had non-high-risk B-cell precursor ALL. Patients with standard-risk ALL, who received the longest maintenance therapy, had the highest adjusted hazard of second cancer (hazard ratio [HR], intermediate vs. standard risk: 0.16, 95% CI: 0.06-0.43, P < 0.001; HR, high vs. standard risk: 0.09, 95% CI: 0.02-0.49, P = 0.006); no significant effects of protocol, age, or white blood cell count at diagnosis, ALL HeH, or t(12;21)[ETV6/RUNX1] were observed. A subset analysis on the patients with standard-risk ALL did not show an increased hazard of second cancer from either HeH or t(12;21) (adjusted HR 2.02, 95% CI: 0.69-5.96, P = 0.20). The effect of low TPMT low activity was explored in patients reaching maintenance therapy in clinical remission (n = 3,368); no association with second cancer was observed (adjusted HR 1.43, 95% CI: 0.54-3.76, P = 0.47).

CONCLUSIONS: The rate of second cancer was generally highest in patients with low-risk ALL, but we could not identify a subset at higher risk than others.

Original languageEnglish
Article numbere26518
JournalPediatric Blood & Cancer
Issue number10
Pages (from-to)1-9
Number of pages9
Publication statusPublished - Oct 2017

    Research areas

  • Adolescent, Antineoplastic Combined Chemotherapy Protocols, Child, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 21, Female, Follow-Up Studies, Humans, Male, Methyltransferases, Neoplasms, Second Primary, Ploidies, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Retrospective Studies, Risk Factors, Translocation, Genetic, Journal Article

ID: 184633904