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

Artikel i vetenskaplig tidskrift
Författare S. N. Nielsen
F. Eriksson
S. Rosthoej
M. K. Andersen
E. Forestier
H. Hasle
L. L. Hjalgrim
A. Aasberg
Jonas Abrahamsson
M. Heyman
O. G. Jonsson
K. Pruunsild
G. E. Vaitkeviciene
K. Vettenranta
K. Schmiegelow
Publicerad i Pediatr Blood Cancer
Volym 64
Nummer/häfte 10
ISSN 1545-5009
Publiceringsår 2017
Publicerad vid Institutionen för kliniska vetenskaper, sektionen för kvinnors och barns hälsa, Avdelningen för pediatrik
Språk English
Länkar doi.org/10.1002/pbc.26518
Ämnesord childhood acute lymphoblastic leukemia, 6-mercaptopurine, methotrexate, second cancer, childhood-cancer, nordic countries, malignant neoplasms, maintenance, therapy, nopho all-92, cumulative incidence, myeloid-leukemia, survivors, methotrexate/6-mercaptopurine, epipodophyllotoxins, Oncology, Hematology, Pediatrics
Ämneskategorier Pediatrik

Sammanfattning

BackgroundThe 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. ProcedureWe 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]. ResultsAfter 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). ConclusionsThe 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.

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