S Rosthoej

Aalborg University Hospital, Ålborg, North Denmark, Denmark

Are you S Rosthoej?

Claim your profile

Publications (5)32.33 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse was increased 2.9-fold for patients with the 1199GA variant versus 1199GG (P=0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or 3435TT variants versus 3435CC (overall P=0.02). The degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P=0.01/P<0.0001). We observed more liver toxicity after high-dose methotrexate in patients with 3435CC variant versus 3435CT/TT (P=0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms, efficacy and toxicity in the treatment of ALL, and ABCB1 1199G>A may be a new possible predictive marker for outcome in childhood ALL.The Pharmacogenomics Journal advance online publication, 13 January 2015; doi:10.1038/tpj.2014.81.
    Full-text · Article · Jan 2015 · The Pharmacogenomics Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours and has higher affinity and selectivity to the 5-HT(3) receptor. Adult studies have demonstrated that palonosetron is both more effective and require fewer administrations than first generation 5-HT(3) receptor antagonists. The purpose of this study was to examine the effect of a single dose of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2) . Between January 2010 and December 2010, 138 courses, originating from 53 children, were included from four Danish Childhood Cancer Centers. Information regarding emetic episodes, rescue therapy, and nausea were recorded prospectively on questionnaires. Complete response (no emesis and no rescue therapy) was achieved in 84.1% of courses during the acute (0-24 hours post-chemotherapy) and in 60.1% during the delayed phase (24-66 hours post-chemotherapy). 92.0% of courses were free of emesis during the acute, and 86.2% were free of emesis during the delayed phase. 76.8% of courses were free of nausea during the acute, and 78.3% were free of nausea during the delayed phase. A single dose of palonosetron-without concomitant corticosteroid-was effective in preventing both acute and delayed phase CINV in majority of children with ALL treated with HD-MTX. Pediatr Blood Cancer 2012; 59: 870-873. © 2012 Wiley Periodicals, Inc.
    No preview · Article · Nov 2012 · Pediatric Blood & Cancer
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (>or=10 years) and 176 non-adolescents (<10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) <50 x 10(9)/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS(12y):0.71 vs 0.83, P=0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r(S)=0.36, P=0.02), which became nonsignificant for those who relapsed (r(S)=0.05, P=0.9). The best-fit multivariate Cox regression model to predict risk of relapse included mWBC and thiopurine methyltransferase activity, which methylates mercaptopurine and reduces the intracellular availability of cytotoxic 6-thioguanine nucleotides (coefficient: 0.11, P=0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient=0.65, P=0.003) than for non-adolescents (coefficient=0.42, P=0.04). Adolescents had higher mean neutrophil counts (P=0.002) than non-adolescents, but received nonsignificantly lower mercaptopurine and MTX doses during maintenance therapy. Red blood cell MTX levels were significantly related to the dose of MTX among adolescents who stayed in remission (r(S)=0.38, P=0.02), which was not the case for those who developed a relapse (r(S)=0.15, P=0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.
    Full-text · Article · Apr 2010 · Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G>A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA variants (P = .046). Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant. In a subset of 182 children receiving 608 high-dose MTX courses, we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants (platelet 73 vs 99/105 x 10(9)/L, P = .004, hemoglobin 5.6 vs 5.9/6.0 mmol/L, P = .004) and a higher degree of liver toxicity in patients with RFC GG variant (alanine aminotransferase 167 vs 127/124 U/L, P = .05). In conclusion, the RFC 80G>A polymorphism interacts with chromosome 21 copy numbers and affects both efficacy and toxicity of MTX.
    Full-text · Article · Mar 2010 · Blood
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Treatment results for neuroblastoma in Denmark have been poorer than in other Nordic countries, so we investigated whether a change in incidence, stage distribution and survival had occurred between 1981 and 2000. Clinical data were retrieved from the medical charts of 160 children <15 years of age with extra-cranial neuroblastoma (n=139) or ganglioneuroblastoma (n=21) diagnosed in Denmark between 1981 and 2000. The minimal follow-up time was 52 months. Statistical analyses were performed in STATA. The incidence was 8.55 per million children below 15 years of age (world standard 9.6) and 42.6 per million children below 12 months of age, and it has remained unchanged since 1970. The median age at diagnosis was 27 months. In all, 32% of the children were aged below 12 months at diagnosis, 53% had metastatic disease and in 12% the diagnosis was made incidentally. Prognostic factors such as age, stage and site of primary tumour were the same as in other studies and did not change. During the study period, the mortality rate decreased steadily, and the 5-year survival rate increased from 38% in 1981-1985 to 59% in 1996-2000, corresponding to the level found in other Western countries. Increased survival was also seen in children with metastatic disease. Participation in international studies, better supportive care and possibly postoperative autologous stem cell transplantation may have contributed to the increased survival.
    Full-text · Article · Feb 2009 · British Journal of Cancer

Publication Stats

69 Citations
32.33 Total Impact Points


  • 2009-2015
    • Aalborg University Hospital
      • Department of Pediatrics
      Ålborg, North Denmark, Denmark
  • 2012
    • Aarhus University Hospital
      • Department of Pediatrics
      Aarhus, Central Jutland, Denmark