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dc.contributor.authorLevinsen, Mette
dc.contributor.authorShabaneh, Diana
dc.contributor.authorBohnstedt, Cathrine
dc.contributor.authorHarila-Saari, Arja
dc.contributor.authorJonsson, Olafur G
dc.contributor.authorKanerva, Jukka
dc.contributor.authorLindblom, Anna
dc.contributor.authorLund, Bendik
dc.contributor.authorAndersen, Elisabeth W
dc.contributor.authorSchmiegelow, Kjeld
dc.date.accessioned2013-08-30T13:27:24Z
dc.date.available2013-08-30T13:27:24Z
dc.date.issued2012-01
dc.date.submitted2013-08-30
dc.identifier.citationEur. J. Haematol. 2012, 88(1):78-86en_GB
dc.identifier.issn1600-0609
dc.identifier.pmid21854453
dc.identifier.doi10.1111/j.1600-0609.2011.01695.x
dc.identifier.urihttp://hdl.handle.net/2336/300428
dc.descriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractTrimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during maintenance therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never received TMP/SMX (TMP/SMX(never) ). Ten patients (all TMP/SMX(never) ) developed PCP, eight of which occurred within 7 months from the start of maintenance therapy. The TMP/SMX(2-7) group received lower oral 6MP doses than TMP/SMX(never) patients (50.6 vs. 63.9 mg/m(2) /d; P<0.001) but had lower absolute neutrophil counts (ANC) (median 1.7 vs. 2.0 × 10(9) /L; P<0.001). In Cox multivariate analysis, higher ANC levels (P=0.04) and male gender (P=0.06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX(2-7) patients (P=0.40) but did for TMP/SMX(never) patients (P=0.02). The difference in the effect on EFS between TMP/SMX(2-7) and TMP/SMX(never) patients was not significant (P=0.46). EFS did not differ between TMP/SMX(2-7) and TMP/SMX(never) patients (0.83 vs. 0.83; P=0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy.
dc.description.sponsorshipDanish Childhood Cancer Foundation Danish Council for Independent Research 09-075100 Danish Cancer Society R15-A719-09-S7 Nordic pediatric oncology centersen_GB
dc.language.isoenen
dc.publisherWiley-Blackwellen_GB
dc.relation.urlhttp://dx.doi.org/10.1111/j.1600-0609.2011.01695.xen_GB
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1111/j.1600-0609.2011.01695.x/pdfen_GB
dc.rightsArchived with thanks to European journal of haematologyen_GB
dc.subject.mesh6-Mercaptopurineen_GB
dc.subject.meshAdministration, Oralen_GB
dc.subject.meshAnti-Infective Agentsen_GB
dc.subject.meshAntineoplastic Combined Chemotherapy Protocolsen_GB
dc.subject.meshChilden_GB
dc.subject.meshChild, Preschoolen_GB
dc.subject.meshDisease-Free Survivalen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMethotrexateen_GB
dc.subject.meshPneumocystis jiroveciien_GB
dc.subject.meshPneumonia, Pneumocystisen_GB
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphomaen_GB
dc.subject.meshTrimethoprim-Sulfamethoxazole Combinationen_GB
dc.titlePneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pediatrics, The University Hospital Rigshospitalet, Copenhagen, Denmark.en_GB
dc.identifier.journalEuropean journal of haematologyen_GB
dc.rights.accessNational Consortium - Landsaðganguren
html.description.abstractTrimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during maintenance therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never received TMP/SMX (TMP/SMX(never) ). Ten patients (all TMP/SMX(never) ) developed PCP, eight of which occurred within 7 months from the start of maintenance therapy. The TMP/SMX(2-7) group received lower oral 6MP doses than TMP/SMX(never) patients (50.6 vs. 63.9 mg/m(2) /d; P<0.001) but had lower absolute neutrophil counts (ANC) (median 1.7 vs. 2.0 × 10(9) /L; P<0.001). In Cox multivariate analysis, higher ANC levels (P=0.04) and male gender (P=0.06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX(2-7) patients (P=0.40) but did for TMP/SMX(never) patients (P=0.02). The difference in the effect on EFS between TMP/SMX(2-7) and TMP/SMX(never) patients was not significant (P=0.46). EFS did not differ between TMP/SMX(2-7) and TMP/SMX(never) patients (0.83 vs. 0.83; P=0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy.


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