The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

K Schmiegelow; Martin Heyman Donovan; Maiken Gustafsson Sherson; B Lausen; F Wesenberg; J Kristinsson; K Vettenranta; H Schroeder; E Forestier; Susanne Rosthøj

doi:10.1038/leu.2009.303

The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

K Schmiegelow, Martin Heyman Donovan, Maiken Gustafsson Sherson, B Lausen, F Wesenberg, J Kristinsson, K Vettenranta, H Schroeder, E Forestier, Susanne Rosthøj

Section of Biostatistics

28 Citations (Scopus)

Abstract

Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (10 years) and 176 non-adolescents (≥10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) 50 × 10 9/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS _12y:0.71 vs 0.83, P0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r S 0.36, P0.02), which became nonsignificant for those who relapsed (r S 0.05, P0.9). 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, P0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient0.65, P0.003) than for non-adolescents (coefficient0.42, P0.04). Adolescents had higher mean neutrophil counts (P0.002) 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, P0.02), which was not the case for those who developed a relapse (r S 0.15, P0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.

Original language	English
Journal	Leukemia
Volume	24
Issue number	4
Pages (from-to)	715-720
Number of pages	6
ISSN	0887-6924
DOIs	https://doi.org/10.1038/leu.2009.303
Publication status	Published - 2010

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Schmiegelow, K., Donovan, M. H., Sherson, M. G., Lausen, B., Wesenberg, F., Kristinsson, J., Vettenranta, K., Schroeder, H., Forestier, E., & Rosthøj, S. (2010). The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse. Leukemia, 24(4), 715-720. https://doi.org/10.1038/leu.2009.303

The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse. / Schmiegelow, K; Donovan, Martin Heyman; Sherson, Maiken Gustafsson et al.
In: Leukemia, Vol. 24, No. 4, 2010, p. 715-720.

Research output: Contribution to journal › Journal article › Research › peer-review

Schmiegelow, K, Donovan, MH, Sherson, MG, Lausen, B, Wesenberg, F, Kristinsson, J, Vettenranta, K, Schroeder, H, Forestier, E & Rosthøj, S 2010, 'The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse', Leukemia, vol. 24, no. 4, pp. 715-720. https://doi.org/10.1038/leu.2009.303

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title = "The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse",

abstract = "Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (10 years) and 176 non-adolescents (≥10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) 50 × 10 9/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS 12y:0.71 vs 0.83, P0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r S 0.36, P0.02), which became nonsignificant for those who relapsed (r S 0.05, P0.9). 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, P0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient0.65, P0.003) than for non-adolescents (coefficient0.42, P0.04). Adolescents had higher mean neutrophil counts (P0.002) 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, P0.02), which was not the case for those who developed a relapse (r S 0.15, P0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.",

author = "K Schmiegelow and Donovan, {Martin Heyman} and Sherson, {Maiken Gustafsson} and B Lausen and F Wesenberg and J Kristinsson and K Vettenranta and H Schroeder and E Forestier and Susanne Rosth{\o}j",

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T1 - The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

AU - Schmiegelow, K

AU - Donovan, Martin Heyman

AU - Sherson, Maiken Gustafsson

AU - Lausen, B

AU - Wesenberg, F

AU - Kristinsson, J

AU - Vettenranta, K

AU - Schroeder, H

AU - Forestier, E

AU - Rosthøj, Susanne

PY - 2010

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N2 - Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (10 years) and 176 non-adolescents (≥10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) 50 × 10 9/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS 12y:0.71 vs 0.83, P0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r S 0.36, P0.02), which became nonsignificant for those who relapsed (r S 0.05, P0.9). 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, P0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient0.65, P0.003) than for non-adolescents (coefficient0.42, P0.04). Adolescents had higher mean neutrophil counts (P0.002) 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, P0.02), which was not the case for those who developed a relapse (r S 0.15, P0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.

AB - Drug doses, blood levels of drug metabolites and myelotoxicity during 6-mercaptopurine/methotrexate (MTX) maintenance therapy were registered for 59 adolescents (10 years) and 176 non-adolescents (≥10 years) with B-cell precursor acute lymphoblastic leukemia (ALL) and a white blood cell count (WBC) 50 × 10 9/l at diagnosis. Event-free survival was lower for adolescents than non-adolescents (pEFS 12y:0.71 vs 0.83, P0.04). For adolescents staying in remission, the mean WBC during maintenance therapy (mWBC) was related to age (r S 0.36, P0.02), which became nonsignificant for those who relapsed (r S 0.05, P0.9). 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, P0.02). The correlation of mWBC to the risk of relapse was more pronounced for adolescents (coefficient0.65, P0.003) than for non-adolescents (coefficient0.42, P0.04). Adolescents had higher mean neutrophil counts (P0.002) 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, P0.02), which was not the case for those who developed a relapse (r S 0.15, P0.60). Thus, compliance to maintenance therapy may influence the risk of relapse for adolescents with ALL.

U2 - 10.1038/leu.2009.303

DO - 10.1038/leu.2009.303

M3 - Journal article

C2 - 20130603

SN - 0887-6924

VL - 24

SP - 715

EP - 720

JO - Leukemia

JF - Leukemia

IS - 4

ER -

The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse

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