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9 results on '"Pruunsild K"'

1. Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting

Author

Modvig, S., Hallböök, H., Madsen, H. O., Siitonen, S., Rosthøj, S., Tierens, A., Juvonen, V., Osnes, L. T. N., Vålerhaugen, H., Hultdin, M., Matuzeviciene, R., Stoskus, M., Marincevic, M., Lilleorg, A., Ehinger, M., Norén-Nystrøm, U., Toft, N., Taskinen, M., Jónsson, O. G., Pruunsild, K., Vaitkeviciene, G., Vettenranta, K., Lund, B., Abrahamsson, J., Porwit, A., Schmiegelow, K., and Marquart, H. V.

Published
2021
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2. Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia

Author

Modvig, S., Madsen, H. O., Siitonen, S. M., Rosthøj, S., Tierens, A., Juvonen, V., Osnes, L.T.N., Vålerhaugen, H., Hultdin, M., Thörn, I., Matuzeviciene, R., Stoskus, M., Marincevic, M., Fogelstrand, L., Lilleorg, A., Toft, N., Jónsson, O. G., Pruunsild, K., Vaitkeviciene, G., Vettenranta, K., Lund, B., Abrahamsson, J., Schmiegelow, K., and Marquart, H. V.

Published
2019
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3. Correction: Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia

Author

Modvig, S., Madsen, H. O., Siitonen, S. M., Rosthøj, S., Tierens, A., Juvonen, V., Osnes, L. T. N., Vålerhaugen, H., Hultdin, M., Thörn, I., Matuzeviciene, R., Stoskus, M., Marincevic, M., Fogelstrand, L., Lilleorg, A., Toft, N., Jónsson, O. G., Pruunsild, K., Vaitkeviciene, G., Vettenranta, K., Lund, B., Abrahamsson, J., Schmiegelow, K., and Marquart, H. V.

Published
2020
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4. Value of flow cytometry for MRD-based relapse prediction in B-cell precursor ALL in a multicenter setting

Author

Modvig, S., primary, Hallböök, H., additional, Madsen, H. O., additional, Siitonen, S., additional, Rosthøj, S., additional, Tierens, A., additional, Juvonen, V., additional, Osnes, L. T. N., additional, Vålerhaugen, H., additional, Hultdin, M., additional, Matuzeviciene, R., additional, Stoskus, M., additional, Marincevic, M., additional, Lilleorg, A., additional, Ehinger, M., additional, Norén-Nystrøm, U., additional, Toft, N., additional, Taskinen, M., additional, Jónsson, O. G., additional, Pruunsild, K., additional, Vaitkeviciene, G., additional, Vettenranta, K., additional, Lund, B., additional, Abrahamsson, J., additional, Porwit, A., additional, Schmiegelow, K., additional, and Marquart, H. V., additional

Published
2020
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5. Correction: Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia

Author

Modvig, S., primary, Madsen, H. O., additional, Siitonen, S. M., additional, Rosthøj, S., additional, Tierens, A., additional, Juvonen, V., additional, Osnes, L. T. N., additional, Vålerhaugen, H., additional, Hultdin, M., additional, Thörn, I., additional, Matuzeviciene, R., additional, Stoskus, M., additional, Marincevic, M., additional, Fogelstrand, L., additional, Lilleorg, A., additional, Toft, N., additional, Jónsson, O. G., additional, Pruunsild, K., additional, Vaitkeviciene, G., additional, Vettenranta, K., additional, Lund, B., additional, Abrahamsson, J., additional, Schmiegelow, K., additional, and Marquart, H. V., additional

Published
2019
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6. Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia

Author

Modvig, S., primary, Madsen, H. O., additional, Siitonen, S. M., additional, Rosthøj, S., additional, Tierens, A., additional, Juvonen, V., additional, Osnes, L.T.N., additional, Vålerhaugen, H., additional, Hultdin, M., additional, Thörn, I., additional, Matuzeviciene, R., additional, Stoskus, M., additional, Marincevic, M., additional, Fogelstrand, L., additional, Lilleorg, A., additional, Toft, N., additional, Jónsson, O. G., additional, Pruunsild, K., additional, Vaitkeviciene, G., additional, Vettenranta, K., additional, Lund, B., additional, Abrahamsson, J., additional, Schmiegelow, K., additional, and Marquart, H. V., additional

Published
2018
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7. Results of NOPHO ALL2008 treatment for patients aged 1–45 years with acute lymphoblastic leukemia

Author

Toft, N, primary, Birgens, H, additional, Abrahamsson, J, additional, Griškevičius, L, additional, Hallböök, H, additional, Heyman, M, additional, Klausen, T W, additional, Jónsson, ÓG, additional, Palk, K, additional, Pruunsild, K, additional, Quist-Paulsen, P, additional, Vaitkeviciene, G, additional, Vettenranta, K, additional, Åsberg, A, additional, Frandsen, T L, additional, Marquart, H V, additional, Madsen, H O, additional, Norén-Nyström, U, additional, and Schmiegelow, K, additional

Published
2017
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8. Results of NOPHO ALL2008 treatment for patients aged 1–45 years with acute lymphoblastic leukemia

Author

Toft, N, Birgens, H, Abrahamsson, J, Griškevicius, L, Hallböök, H, Heyman, M, Klausen, T W, Jónsson, ÓG, Palk, K, Pruunsild, K, Quist-Paulsen, P, Vaitkeviciene, G, Vettenranta, K, Åsberg, A, Frandsen, T L, Marquart, H V, Madsen, H O, Norén-Nyström, U, and Schmiegelow, K

Abstract

Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1–45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1–9 years (A), 266 were 10–17 years (B) and 221 were 18–45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1–3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P=0.53). Event-free survival rates (pEFS5y) were 89±1% (A), 80±3% (B) and 74±4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.

Published
2018
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9. NT5C2 germline variants alter thiopurine metabolism and are associated with acquired NT5C2 relapse mutations in childhood acute lymphoblastic leukaemia.

Author

Tulstrup M, Grosjean M, Nielsen SN, Grell K, Wolthers BO, Wegener PS, Jonsson OG, Lund B, Harila-Saari A, Abrahamsson J, Vaitkeviciene G, Pruunsild K, Toft N, Holm M, Hulegårdh E, Liestøl S, Griskevicius L, Punab M, Wang J, Carroll WL, Zhang Z, Dalgaard MD, Gupta R, Nersting J, and Schmiegelow K

Subjects
Adolescent, Antimetabolites, Antineoplastic therapeutic use, Child, Child, Preschool, DNA metabolism, Female, Gene Frequency drug effects, Gene Frequency genetics, Genome-Wide Association Study methods, Genotype, Humans, Infant, Male, Mercaptopurine therapeutic use, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local metabolism, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Recurrence, Thioguanine metabolism, 5'-Nucleotidase genetics, Germ Cells metabolism, Polymorphism, Single Nucleotide genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma metabolism
Abstract

The antileukaemic drug 6-mercaptopurine is converted into thioguanine nucleotides (TGN) and incorporated into DNA (DNA-TG), the active end metabolite. In a series of genome-wide association studies, we analysed time-weighted means ( wm ) of erythrocyte concentrations of TGN (Ery-TGN) and DNA-TG in 1009 patients undergoing maintenance therapy for acute lymphoblastic leukaemia (ALL). In discovery analyses (454 patients), the propensity for DNA-TG incorporation ( wm DNA-TG/ wm Ery-TGN ratio) was significantly associated with three intronic SNPs in NT5C2 (top hit: rs72846714; P = 2.09 × 10 -10 , minor allele frequency 15%). In validation analyses (555 patients), this association remained significant during both early and late maintenance therapy (P = 8.4 × 10 -6 and 1.3 × 10 -3 , respectively). The association was mostly driven by differences in wm Ery-TGN, but in regression analyses adjusted for wm Ery-TGN (P < 0.0001), rs72846714-A genotype was also associated with a higher wm DNA-TG (P = 0.029). Targeted sequencing of NT5C2 did not identify any missense variants associated with rs72846714 or wm Ery-TGN/ wm DNA-TG. rs72846714 was not associated with relapse risk, but in a separate cohort of 180 children with relapsed ALL, rs72846714-A genotype was associated with increased occurrence of relapse-specific NT5C2 gain-of-function mutations that reduce cytosol TGN levels (P = 0.03). These observations highlight the impact of both germline and acquired mutations in drug metabolism and disease trajectory.

Published
2018
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