EPIDEMIOLOGY OF THERAPY-RELATED MYELOID NEOPLASMS IN THE NORDIC COUNTRIES

Kjeld Schmiegelow
  • Kjeld Schmiegelow
    Faculty of Health Sciences, University of Copenhagen, Pediatric Clinic II, Denmark | kschmiegelow@rh.dk

Abstract

Of 1614 Nordic children with ALL that were treated according to the NOPHO ALL92 protocol, 20 developed an SMN (cumulative risk at 12 years: 1.6%). Sixteen of the twenty SMNs were acute myeloid leukemias or myelodysplasias, and 9 of these had either monosomy 7 (n=7) or 7q deletions (n=2). In Cox multivariate analysis longer duration of oral MTX/6MP maintenance therapy (p=0.02; being longest for standard risk patients) and presence of high-hyperdiploidy (p=0.07) were related to an increased risk of SMN. In 524 patients we determined the erythrocyte activity of thiopurine methyltransferase (TPMT), which methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. The TPMT activity was significantly lower in those that did compared to those that did not develop an SMN (Median: 12.1 vs 18.1 IU/ml; p=0.02). Among 427 TPMT wild type patients, those who developed SMN received higher 6MP doses than the remaining (69.7 vs 60.4 mg/m2, p=0.03), which may reflect increased levels of methylated metabolites that inhibit purine de novo synthesis and thus enhance incorporation of 6-thioguanine nucleotides into DNA. In conclusion, the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMN.

Keywords

: Acute lymphoblastic leukemia, second malignant neoplasm, maintenance therapy, mercaptopurine, thiopurine methyltransferase.

Full Text:

PDF
HTML
Submitted: 2014-06-12 16:03:10
Published: 2011-05-16 00:00:00
Search for citations in Google Scholar
Related articles: Google Scholar
Abstract views:
435

Views:
PDF
106
HTML
976

Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM


Copyright (c) 2016 Mediterranean Journal of Hematology and Infectious Diseases

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Ā 

The Mediterranean Journal of Hematology and Infectious Diseases [eISSN 2035-3006] is owned by the U.C.S.C. and it is published by PAGEPressĀ®, Pavia, Italy. All credits and honors to PKP for their OJS.
 
 
© PAGEPress 2008-2017     -     PAGEPress is a registered trademark property of PAGEPress srl, Italy.     -     VAT: IT02125780185