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

2.50
Hdl Handle:
http://hdl.handle.net/2336/97890
Title:
The degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapse
Authors:
Schmiegelow, K; Heyman, M; Gustafsson, G; Lausen, B; Wesenberg, F; Kristinsson, J; Vettenranta, K; Schroeder, H; Forestier, E; Rosthoej, S
Citation:
Leukemia. 2010, 24(4):715-20
Issue Date:
1-Apr-2010
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.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1038/leu.2009.303

Full metadata record

DC FieldValue Language
dc.contributor.authorSchmiegelow, Ken
dc.contributor.authorHeyman, Men
dc.contributor.authorGustafsson, Gen
dc.contributor.authorLausen, Ben
dc.contributor.authorWesenberg, Fen
dc.contributor.authorKristinsson, Jen
dc.contributor.authorVettenranta, Ken
dc.contributor.authorSchroeder, Hen
dc.contributor.authorForestier, Een
dc.contributor.authorRosthoej, Sen
dc.date.accessioned2010-05-04T15:00:33Z-
dc.date.available2010-05-04T15:00:33Z-
dc.date.issued2010-04-01-
dc.date.submitted2010-05-04-
dc.identifier.citationLeukemia. 2010, 24(4):715-20en
dc.identifier.issn1476-5551-
dc.identifier.pmid20130603-
dc.identifier.doi10.1038/leu.2009.303-
dc.identifier.urihttp://hdl.handle.net/2336/97890-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractDrug 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.en
dc.language.isoenen
dc.publisherNature Publishing Group, Specialist Journalsen
dc.relation.urlhttp://dx.doi.org/10.1038/leu.2009.303en
dc.subject.meshLeukemiaen
dc.subject.meshLymphocyticen
dc.subject.mesh6-Mercaptopurineen
dc.subject.meshAdolescenten
dc.titleThe degree of myelosuppression during maintenance therapy of adolescents with B-lineage intermediate risk acute lymphoblastic leukemia predicts risk of relapseen
dc.typeArticleen
dc.contributor.departmentDepartment of Pediatric Oncology, The University Hospital Rigshospitalet, Copenhagen, Denmark. kschmiegelow@rh.dken
dc.identifier.journalLeukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.Ken

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