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Maintenance therapy and risk of osteonecrosis in children and young adults with acute lymphoblastic leukemia : a NOPHO ALL2008 sub-study

Toksvang, Linea Natalie (författare)
Copenhagen Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Andres-Jensen, Liv (författare)
Copenhagen Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Rank, Cecilie Utke (författare)
Copenhagen Univ Hosp, Pediat Oncol Res Lab, Rigshosp, Copenhagen, Denmark.;Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark.
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Niinimäki, Riitta (författare)
Univ Oulu, Dept Children & Adolescents, Oulu Univ Hosp, Oulu, Finland.;Univ Oulu, PEDEGO Res Unit, Oulu, Finland.
Nersting, Jacob (författare)
Copenhagen Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Nielsen, Stine Nygaard (författare)
Copenhagen Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Mogensen, Signe Sloth (författare)
Copenhagen Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Harila-Saari, Arja H. (författare)
Uppsala universitet,Barnonkologisk och neurologisk forskning
Abrahamsson, Jonas (författare)
Queen Silvia Childrens Hosp, Gothenburg, Sweden.
Joelsson, Joel (författare)
Karolinska Institutet
Overgaard, Ulrik Malthe (författare)
Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark.
Quist-Paulsen, Petter (författare)
Trondheim Reg & Univ Hosp, Trondheim, Norway.
Griskevicius, Laimonas (författare)
Vilnius Univ Hosp, Santaros Klin, Vilnius, Lithuania.;Vilnius Univ, Vilnius, Lithuania.
Jonsson, Olafur Gisli (författare)
Childrens Hosp, Dept Pediat, Reykjavik, Iceland.
Vaitkeviciene, Goda (författare)
Vilnius Univ, Vilnius, Lithuania.;Vilnius Univ Hosp, Ctr Pediat Oncol & Hematol, Santaros Klin, Vilnius, Lithuania.
Frandsen, Thomas Leth (författare)
Copenhagen Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Toft, Nina (författare)
Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark.
Grell, Kathrine (författare)
Copenhagen Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Dept Publ Hlth, Sect Biostat, Copenhagen, Denmark.
Schmiegelow, Kjeld (författare)
Copenhagen Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Med, Inst Clin Med, Copenhagen, Denmark.
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Copenhagen Univ Hosp, Juliane Marie Ctr, Dept Pediat & Adolescent Med, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark Copenhagen Univ Hosp, Pediat Oncol Res Lab, Rigshosp, Copenhagen, Denmark.;Copenhagen Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark. (creator_code:org_t)
2021-06-18
2021
Engelska.
Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer. - 0344-5704 .- 1432-0843. ; 88:5, s. 911-917
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Purpose Osteonecrosis is a burdensome treatment-related toxicity that is mostly diagnosed during or soon after 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy for acute lymphoblastic leukemia (ALL), possibly indicating a pathogenic role of these drugs. Methods We prospectively registered symptomatic osteonecrosis during treatment of 1234 patients aged 1.0-45.9 years treated according to the Nordic Society of Hematology and Oncology (NOPHO) ALL2008 protocol. MTX/6MP metabolites were measured as part of the NOPHO ALL2008 maintenance therapy study. Results After a median follow-up of 5.6 years [interquartile range (IQR) 3.6-7.5], 68 patients had been diagnosed with symptomatic osteonecrosis. The cumulative incidence was 2.7% [95% confidence interval (CI) 1.6-3.8%] for patients aged < 10 years, 14.9% (95% CI 9.7-20.2%) for patients aged 10.0-17.9 years, and 14.4% (95% CI 8.0-20.8%) for patients aged >= 18 years. The median time from diagnosis of ALL to diagnosis of osteonecrosis in these age groups was 1.0 year (IQR 0.7-2.0), 2.0 years (IQR 1.1-2.4), and 2.2 years (IQR 1.8-2.8), respectively (p = 0.001). With 17,854 blood samples available for MTX and 6MP metabolite analysis, neither erythrocyte levels of 6-thioguanine (TG) nucleotides (p > 0.99), methylated 6MP metabolites (p = 0.37), MTX polyglutamates (p = 0.98) nor DNA-TG (p = 0.53) were significantly associated with the hazard of osteonecrosis in Cox models stratified by the three age groups and adjusted for sex. Conclusion Maintenance therapy intensity determined by 6MP and MTX metabolites was not associated with the risk of developing osteonecrosis in the NOPHO ALL2008 cohort.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Acute lymphoblastic leukemia
Maintenance
Mercaptopurine
Osteonecrosis
Pharmacokinetics

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