Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers
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Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers. / Nielsen, Stine N.; Eriksson, 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.
In: Pediatric Blood & Cancer, Vol. 64, No. 10, e26518, 10.2017, p. 1-9.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Children with low-risk acute lymphoblastic leukemia are at highest risk of second cancers
AU - Nielsen, Stine N.
AU - Eriksson, Frank
AU - Rosthoej, Susanne
AU - Andersen, Mette K.
AU - Forestier, Erik
AU - Hasle, Henrik
AU - Hjalgrim, Lisa L.
AU - Aasberg, Ann
AU - Abrahamsson, Jonas
AU - Heyman, Mats
AU - Jónsson, Ólafur G.
AU - Pruunsild, Kaie
AU - Vaitkeviciené, Goda E.
AU - Vettenranta, Kim
AU - Schmiegelow, Kjeld
N1 - © 2017 Wiley Periodicals, Inc.
PY - 2017/10
Y1 - 2017/10
N2 - 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.
AB - 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.
KW - Adolescent
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Child
KW - Chromosomes, Human, Pair 12
KW - Chromosomes, Human, Pair 21
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Male
KW - Methyltransferases
KW - Neoplasms, Second Primary
KW - Ploidies
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma
KW - Retrospective Studies
KW - Risk Factors
KW - Translocation, Genetic
KW - Journal Article
U2 - 10.1002/pbc.26518
DO - 10.1002/pbc.26518
M3 - Journal article
C2 - 28500740
VL - 64
SP - 1
EP - 9
JO - Pediatric Blood & Cancer
JF - Pediatric Blood & Cancer
SN - 1545-5009
IS - 10
M1 - e26518
ER -
ID: 184633904