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Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers
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2017 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 64, no 10, e26518Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2017. Vol. 64, no 10, e26518
Keyword [en]
childhood acute lymphoblastic leukemia, 6-mercaptopurine, methotrexate, second cancer
National Category
Cancer and Oncology Hematology Pediatrics
Identifiers
URN: urn:nbn:se:umu:diva-139123DOI: 10.1002/pbc.26518ISI: 000408045800011OAI: oai:DiVA.org:umu-139123DiVA: diva2:1147517
Available from: 2017-10-06 Created: 2017-10-06 Last updated: 2017-10-06Bibliographically approved

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