EPIDEMIOLOGY OF THERAPY-RELATED MYELOID NEOPLASMS IN THE NORDIC COUNTRIES
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 mult...
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PAGEPress Publications
2011-05-01
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| Series: | Mediterranean Journal of Hematology and Infectious Diseases |
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| Online Access: | http://www.mjhid.org/index.php/mjhid/article/view/288 |
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| author | Kjeld Schmiegelow |
| author_facet | Kjeld Schmiegelow |
| author_sort | Kjeld Schmiegelow |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-71302012a72e44dd8c1f8ba24527e6e7 |
| institution | Kabale University |
| issn | 2035-3006 |
| language | English |
| publishDate | 2011-05-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | Mediterranean Journal of Hematology and Infectious Diseases |
| spelling | doaj-art-71302012a72e44dd8c1f8ba24527e6e72025-01-02T06:30:12ZengPAGEPress PublicationsMediterranean Journal of Hematology and Infectious Diseases2035-30062011-05-0131e2011020e201102010.4084/mjhid.2011.020180EPIDEMIOLOGY OF THERAPY-RELATED MYELOID NEOPLASMS IN THE NORDIC COUNTRIESKjeld Schmiegelow0Faculty of Health Sciences, University of Copenhagen, Pediatric Clinic IIOf 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.http://www.mjhid.org/index.php/mjhid/article/view/288: Acute lymphoblastic leukemia, second malignant neoplasm, maintenance therapy, mercaptopurine, thiopurine methyltransferase. |
| spellingShingle | Kjeld Schmiegelow EPIDEMIOLOGY OF THERAPY-RELATED MYELOID NEOPLASMS IN THE NORDIC COUNTRIES Mediterranean Journal of Hematology and Infectious Diseases : Acute lymphoblastic leukemia, second malignant neoplasm, maintenance therapy, mercaptopurine, thiopurine methyltransferase. |
| title | EPIDEMIOLOGY OF THERAPY-RELATED MYELOID NEOPLASMS IN THE NORDIC COUNTRIES |
| title_full | EPIDEMIOLOGY OF THERAPY-RELATED MYELOID NEOPLASMS IN THE NORDIC COUNTRIES |
| title_fullStr | EPIDEMIOLOGY OF THERAPY-RELATED MYELOID NEOPLASMS IN THE NORDIC COUNTRIES |
| title_full_unstemmed | EPIDEMIOLOGY OF THERAPY-RELATED MYELOID NEOPLASMS IN THE NORDIC COUNTRIES |
| title_short | EPIDEMIOLOGY OF THERAPY-RELATED MYELOID NEOPLASMS IN THE NORDIC COUNTRIES |
| title_sort | epidemiology of therapy related myeloid neoplasms in the nordic countries |
| topic | : Acute lymphoblastic leukemia, second malignant neoplasm, maintenance therapy, mercaptopurine, thiopurine methyltransferase. |
| url | http://www.mjhid.org/index.php/mjhid/article/view/288 |
| work_keys_str_mv | AT kjeldschmiegelow epidemiologyoftherapyrelatedmyeloidneoplasmsinthenordiccountries |