Kjeld Schmiegelow

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Analysis of 2668 children with acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors. Improvements in systemic and intrathecal chemotherapy have(More)
The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic(More)
Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs. TPMT activity is regulated by a common genetic polymorphism that is associated with large individual variations in thiopurine toxicity and efficacy. We previously cloned the functional gene for human TPMT and reported a common variant allele for low enzyme activity,(More)
Seventy percent of children with cancer survive. Radiation and chemotherapy may, however, impair ovarian function. The aim of this population-based study was to achieve a comprehensive knowledge of the degree of ovarian damage. Ovarian function was evaluated in 100 childhood cancer survivors and 21 controls of similar age. Menstrual cycle pattern was(More)
In this population-based material from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2860 children below 15 years of age were diagnosed with acute lymphoblastic leukemia (ALL) from July 1981 to June 1998. The annual incidence was 3.9/100,000 children and was stable throughout the study period. The development from regional or(More)
As the cure rates for haematological malignancies have improved, the exploration of the balance between efficacy and side effects has become a major research target. The antifolate methotrexate is widely used in the treatment of acute lymphoblastic leukaemia, non-Hodgkin lymphoma, and osteosarcoma. Even when given identical methotrexate doses, patients vary(More)
Thiopurine methyltransferase (TPMT) activity exhibits monogenic co-dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, homozygous TPMT-deficient patients (~1 in 178 to 1 in 3,736 individuals with two nonfunctional TPMT alleles) experience severe myelosuppression, 30-60% of(More)
Assessment of minimal residual disease (MRD) has acquired a prominent position in European treatment protocols for patients with acute lymphoblastic leukemia (ALL), on the basis of its high prognostic value for predicting outcome and the possibilities for implementation of MRD diagnostics in treatment stratification. Therefore, there is an increasing need(More)
BACKGROUND Compelling evidence suggests that childhood leukemia often originates in utero. Birth weight is one of the few pregnancy-related risk factors that has been associated with leukemia risk, but the association has remained poorly characterized. We conducted a population-based case-control study in Denmark, Sweden, Norway, and Iceland to investigate(More)
The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Methyltransferase Genotype and Thiopurine Dosing was originally published in March 2011. We reviewed recent literature and concluded that although relevant new evidence has been generated, none of the evidence would change the primary dosing recommendations in the(More)