Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers.
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Authors
Nielsen, Stine NEriksson, Frank
Rosthoej, Susanne
Andersen, Mette K
Forestier, Erik
Hasle, Henrik
Hjalgrim, Lisa L
Aasberg, Ann
Abrahamsson, Jonas
Heyman, Mats
Jónsson, Ólafur G
Pruunsild, Kaie
Vaitkeviciené, Goda E
Vettenranta, Kim
Schmiegelow, Kjeld
Issue Date
2017-10
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Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers. 2017, 64 (10) Pediatr Blood CancerAbstract
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.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].
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).
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.
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Archived with thanks to Pediatric blood & cancerae974a485f413a2113503eed53cd6c53
10.1002/pbc.26518
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