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Methotrexate/6-merc...
Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study.
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- Schmiegelow, Kjeld (author)
- Rigshospital
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- Al-Modhwahi, Ibrahim (author)
- Rigshospital
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Andersen, Mette Klarskov (author)
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- Behrendtz, Mikael (author)
- Östergötlands Läns Landsting,Barn- och ungdomskliniken i Linköping
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- Forestier, Erik (author)
- Umeå universitet,Pediatrik,Umeå University Hospital
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- Hasle, Henrik (author)
- Aarhus University Hospital
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- Heyman, Mats (author)
- Karolinska Institutet,Astrid Lindgrens Barnsjukhus
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- Kristinsson, Jon (author)
- University Hospital, Reykjavik
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- Nersting, Jacob (author)
- University Hospital, Trondheim
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Nygaard, Randi (author)
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- Svendsen, Anne Louise (author)
- University of Copenhagen
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- Vettenranta, Kim (author)
- University Hospital, Helsinki
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- Weinshilboum, Richard (author)
- Mayo Clinic
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- Kriström, Berit, 1949 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics
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- Mellander, Lotta, 1941 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics
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(creator_code:org_t)
- American Society of Hematology, 2009
- 2009
- English.
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 113:24, s. 6077-84
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16 acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P = .07) were related to increased risk of SMN. Thiopurine methyltransferase (TPMT) methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. Of 524 patients who had erythrocyte TPMT activity measured, the median TPMT activity in 9 patients developing an SMN was significantly lower than in the 515 that did not develop an SMN (median, 12.1 vs 18.1 IU/mL; P = .02). Among 427 TPMT wild-type patients for whom the 6MP dose was registered, those who developed SMN received higher average 6MP doses than the remaining patients (69.7 vs 60.4 mg/m2; P = .03). This study indicates that the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMNs in childhood ALL.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
Keyword
- 6-Mercaptopurine
- administration & dosage
- adverse effects
- Administration
- Oral
- Adolescent
- Antineoplastic Combined Chemotherapy Protocols
- adverse effects
- Child
- Child
- Preschool
- Combined Modality Therapy
- Cranial Irradiation
- Female
- Follow-Up Studies
- Humans
- Immunoenzyme Techniques
- Infant
- Karyotyping
- Male
- Methotrexate
- administration & dosage
- adverse effects
- Methyltransferases
- metabolism
- Neoplasms
- Second Primary
- chemically induced
- diagnosis
- metabolism
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- drug therapy
- pathology
- radiotherapy
- Prognosis
- Remission Induction
- Risk Factors
- Stem Cell Transplantation
- Survival Rate
- Treatment Outcome
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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Blood
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- By the author/editor
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Schmiegelow, Kje ...
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Al-Modhwahi, Ibr ...
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Andersen, Mette ...
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Behrendtz, Mikae ...
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Forestier, Erik
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Hasle, Henrik
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Heyman, Mats
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Kristinsson, Jon
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Nersting, Jacob
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Nygaard, Randi
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Svendsen, Anne L ...
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Vettenranta, Kim
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Weinshilboum, Ri ...
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Kriström, Berit, ...
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Mellander, Lotta ...
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- 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 Pediatrics
- Articles in the publication
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Blood
- By the university
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University of Gothenburg
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Umeå University
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Karolinska Institutet
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Linköping University