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No association betw...
No association between relapse hazard and thiopurine methyltransferase geno- or phenotypes in non-high risk acute lymphoblastic leukemia: a NOPHO ALL2008 sub-study
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- Nielsen, S. N. (author)
- Univ Copenhagen, Denmark
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- Toksvang, L. N. (author)
- Univ Copenhagen, Denmark
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- Grell, K. (author)
- Univ Copenhagen, Denmark; Univ Copenhagen, Denmark
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- Nersting, J. (author)
- Univ Copenhagen, Denmark
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- Abrahamsson, Jonas, 1954 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics,Univ Gothenburg, Sweden
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- Lund, B. (author)
- Norwegian Univ Sci & Technol, Norway
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- Kanerva, J. (author)
- Univ Helsinki, Finland; Univ Helsinki, Finland
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- Jonsson, O. G. (author)
- Landspitali Univ Hosp, Iceland
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- Vaitkeviciene, G. (author)
- Vilnius Univ, Lithuania
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- Pruunsild, K. (author)
- Tallinn Childrens Hosp, Estonia
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- Lindqvist Appell, Malin (author)
- Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten
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- Hjalgrim, L. L. (author)
- Univ Copenhagen, Denmark
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- Schmiegelow, K. (author)
- Univ Copenhagen, Denmark; Univ Copenhagen, Denmark
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(creator_code:org_t)
- 2021-04-29
- 2021
- English.
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In: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 88, s. 271-279
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https://doi.org/10.1...
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Abstract
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- Purpose 6-mercaptopurine(6MP)/methotrexate maintenance therapy is essential to reduce relapse of childhood acute lymphoblastic leukemia (ALL). Common germline variants in TPMT cause low activity of thiopurine methyltransferase (TPMT) and higher 6MP metabolite (TGN) levels. Higher levels of TGNs incorporated into DNA (DNA-TG) and low TPMT activity have previously been associated with a lower relapse risk. We explored if TPMT geno- or phenotype was associated with DNA-TG levels and relapse rate in NOPHO ALL2008. Methods TPMT genotype, repeated phenotyping, and DNA-TG measurements were collected in 918 children with non-high risk ALL (NOPHO ALL2008 maintenance therapy study). Maintenance therapy started with 6MP at 50 and 75 mg/m(2) for TPMT heterozygous and wildtype patients and was adjusted to a target WBC of 1.5 - 3.0 x 10(9)/L. Results Of 918 patients, 78 (8.5%) were TPMT heterozygous and 903 had at least one TPMT measurement (total 3063). Mean TPMT activities were higher with wildtype than heterozygous TPMT (N = 752, 16.6 versus 9.6 U/mL ery., p < 0.001). The 5-year cumulative incidence of relapse was 6.4% and 6.0% for TPMT heterozygous and wildtype patients, and there was no association between genotype and relapse rate (N = 918, hazard ratio = 1.01, 95% confidence interval [CI] 0.40 - 2.54, p = 0.98). Although TPMT heterozygous patients had higher DNA-TG (N = 548, median 760.9 [interquartile range (IQR) 568.7 - 890.3] versus 492.7 [IQR 382.1 - 634.6] fmol/mu g, p < 0.001), TPMT activity was not associated with relapse rate (N = 813; hazard ratio = 0.98 per one U/mL ery. increase in TPMT activity, 95% CI 0.91 - 1.06, p = 0.67). Conclusion TPMT geno- and phenotype were not associated with relapse in non-high risk NOPHO ALL2008.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
Keyword
- Childhood acute lymphoblastic leukemia
- Maintenance therapy
- 6-mercaptopurine
- Thiopurine methyltransferase
- Relapse
- Oncology
- Pharmacology & Pharmacy
- Childhood acute lymphoblastic leukemia; Maintenance therapy; 6-mercaptopurine; Thiopurine methyltransferase; Relapse
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Nielsen, S. N.
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Toksvang, L. N.
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Grell, K.
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Nersting, J.
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Abrahamsson, Jon ...
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Lund, B.
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show more...
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Kanerva, J.
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Jonsson, O. G.
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Vaitkeviciene, G ...
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Pruunsild, K.
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Lindqvist Appell ...
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Hjalgrim, L. L.
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Schmiegelow, K.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Pediatrics
- Articles in the publication
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Cancer Chemother ...
- By the university
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University of Gothenburg
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Linköping University