| 1. |
- Honkaniemi, Emma, et al.
(författare)
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Acquired aplastic anaemia in seven children with severe hepatitis with or without liver failure
- 2007
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 96:11, s. 1660-1664
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Aplastic anaemia following hepatitis may develop in as many as 1 of 3 patients with non-A, non-B and non-C hepatitis. Several causative factors have been discussed, such as viral infections and autoimmunity. Here we describe the natural history of this condition in 7 children and investigate possible hepatitis-causing agents. Methods: We reviewed the medical records, bone marrow and liver biopsies of 7 children with severe hepatitis, with or without liver failure, who subsequently had developed aplastic anaemia. Results: The median time from onset of hepatic symptoms until diagnosed onset of aplasia was 54 days. No associated viral infections could be identified. On liver biopsy, a majority had lobular inflammation but lacked signs of autoimmune hepatitis, findings compatible with a viral aetiology. Three of 6 children had low reticulocyte counts already at onset of hepatitis. All, but one patient is alive at median follow-up of 8 years. Conclusion: The unknown pathogenetic mechanism appears to target liver and bone marrow simultaneously, because half of the children concomitantly had low reticulocyte counts and severe liver failure.
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| 2. |
- Rubin, Johanna, et al.
(författare)
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Intrathecal chemoprophylaxis after HSCT in children
- 2008
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Ingår i: Pediatric Transplantation. - : Wiley. - 1397-3142 .- 1399-3046. ; 12:8, s. 889-895
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Tidskriftsartikel (refereegranskat)abstract
- At present, the literature on the efficacy and risks of i.t. chemotherapy to children after HSCT is scarce. Current practices to reduce the risk of leukemic relapse in the CNS after HSCT differ between centers of transplantation. We compared 74 patients (56 ALL/18 AML), who received i.t. therapy post-HSCT with 46 patients (36 ALL/10 AML) who did not receive post-HSCT i.t. therapy. The patients were transplanted at the University Children's Hospital, Uppsala or the Karolinska University Hospital, Huddinge, two Swedish transplantation units with different routines concerning i.t. therapy after HSCT. The primary end-point was the number of isolated CNS relapses. Secondary end-points were other types of relapse, death, and neurological complications. There was no statistically significant difference in the incidence of CNS relapses between the groups (p > 0.05). I.t. therapy did not reduce the overall incidence of isolated CNS relapse or mortality. Our study did not demonstrate a protective effect of i.t. therapy indicating that post-HSCT i.t. therapy may only be of limited use in the treatment of acute childhood leukemia. We conclude that with the risks present, i.t. therapy should be carefully evaluated, and only considered in high-risk cases.
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| 3. |
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| 4. |
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| 5. |
- Lönnerholm, Gudmar, et al.
(författare)
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In vitro cellular drug sensitivity at diagnosis is correlated to minimal residual disease at end of induction therapy in childhood acute lymphoblastic leukemia.
- 2009
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Ingår i: Leukemia research. - Oxford : Elsevier BV. - 0145-2126 .- 1873-5835. ; 33:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Leukemic cells from 85 children with newly diagnosed precursor B-lineage ALL were tested for in vitro drug sensitivity to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. There was a significant correlation between MRD day 29 and in vitro sensitivity to prednisolone (p<0.001) and doxorubicin (p=0.017), drugs administered during induction therapy. In patients with t(12;21) (n=20), in vitro sensitivity to doxorubicin was an independent factor for MRD <0.1% (p=0.031; R(2)=0.66). Thus, data show that in vitro drug sensitivity at diagnosis is correlated to cell kill during induction therapy as measured by MRD day 29.
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| 6. |
- Lönnerholm, Gudmar, et al.
(författare)
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Vincristine pharmacokinetics in children with Down syndrome
- 2009
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 52:1, s. 123-125
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Tidskriftsartikel (refereegranskat)abstract
- Children with Down syndrome (DS), who represent about 2% of childhood acute lymphoblastic leukemia, have inferior prognosis compared to non-DS children. For vincristine (and many other anticancer agents) pharmacokinetic data are scant or missing, and there is considerable uncertainty about the optimal dosing of drugs to patients with DS. We studied vincristine pharmacokinetics on treatment day one in six children with DS and compared to 92 non-DS children. No differences were found. Thus, we found no rationale for dose reduction of vincristine in DS children from a strictly pharmacokinetic point of view.
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| 7. |
- Lönnerholm, Gudmar, et al.
(författare)
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Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia.
- 2008
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Ingår i: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 142:4, s. 616-21
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Tidskriftsartikel (refereegranskat)abstract
- Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We here report clinical data (median follow-up time 10.5 years, range 7.3-12 years) for 86 children with B-cell precursor ALL, in whom vincristine kinetics were studied on treatment day 1. The median total plasma clearance was 429 and 331 ml/min per m(2) and the area under the plasma concentration-time curve (AUC) was 4.49 and 5.40 mg/l x min in relapse and non-relapse patients, respectively (not significant). In standard risk patients, where treatment depends more heavily on vincristine than in other subgroups, the relative risk (RR) of relapse was significantly increased for patients with clearance values above median (RR 5.2; P = 0.036), or AUC values below median (RR 5.8; P = 0.025). Our data suggest a relationship between the antileukemic effect and the systemic exposure of the drug, which warrants further studies.
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| 8. |
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| 9. |
- Palle, Josefine, et al.
(författare)
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Doxorubicin pharmacokinetics is correlated to the effect of induction therapy in children with acute myeloid leukemia
- 2006
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Ingår i: Anti-Cancer Drugs. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4973 .- 1473-5741. ; 17:4, s. 385-392
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Tidskriftsartikel (refereegranskat)abstract
- We studied the pharmacokinetics of doxorubicin in 41 children treated for newly diagnosed acute myeloid leukemia. Doxorubicin, 75 mg/m(2) body surface area, was administered by constant i.v. infusion over 8 h. Four children with Down's syndrome (DS), 1.2-2.3 years old, had a median total body clearance of 523 ml/min/m(2). The median clearance in non-DS children, 0.6-1.8 years old (n=4) and 2.5-17.7 years old (n=33), was 446 and 538 ml/min/m(2), respectively. Patients who went into complete remission (CR) after induction therapy had a significantly higher median plasma concentration of doxorubicin than those who did not, 249 compared with 180 ng/ml, respectively (P=0.036; analysis restricted to non-DS patients). Doxorubicin plasma concentration was an independent factor for CR, both in univariate (P=0.031) and multivariate analysis including sex, age and white blood cell count at diagnosis (P=0.021). Patients who reached CR had a significantly lower doxorubicin clearance than those who did not, 513 and 657 ml/min/m(2), respectively (P=0.017). In conclusion, doxorubicin plasma concentration and total body clearance during up-front treatment were correlated to the effect of induction therapy. Prospective studies should be performed to confirm the concentration-effect relationship and explore the possibility of therapeutic monitoring.
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| 10. |
- Palle, Josefine, et al.
(författare)
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Etoposide pharmacokinetics in children treated for acute myeloid leukemia
- 2006
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Ingår i: Anti-Cancer Drugs. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4973 .- 1473-5741. ; 17:9, s. 1087-1094
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Tidskriftsartikel (refereegranskat)abstract
- We studied the pharmacokinetics of etoposide in 45 children treated for newly diagnosed acute myeloid leukemia. Etopcoside, 100 mg/m(2) body surface area/24h, was administered by 96-h continuous intravenous infusion. Concomitantly, the children received cytarabine 200 mg/m(2)/24 h by intravenous infusion and 6-thioguanine 100 mg/m(2) twice daily orally. Median total body clearance in children 0.5-11.8 (n=4) and 2.3-17.7 years old (n=36) without Down's syndrome was 17.1 and 17.6 ml/min/m(2), respectively (P=0.96). Five children with Down's syndrome had a median clearance of 13.6 ml/min/m(2) (P=0.067 compared with non-Down's syndrome children). Eighteen of the children received a second identical treatment course 3-4 weeks later; there was a significant correlation between individual clearance values (p=0.56; P=0.017). We found no significant correlation between etoposide pharmacolkinetics and the remission rate or the relapse rate. In conclusion, our findings indicate that special dose-calculation guidelines for infants above 3 months old are not substantiated by age-dependent pharmacolkinetics of etoposide. Down's syndrome children might be candidates for dose reduction if our data are confirmed in larger numbers of patients. Low course-to-course variability indicates that pharmacolkinetically guided dosing of etoposide might be clinically relevant, if larger studies can demonstrate that this approach decreases toxicity or increases response rates.
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