title: Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia.
abstract: Trimethoprim-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.
authors.affiliation: Department of Pediatrics, The University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Levinsen
authors.forename: Diana
authors.initials: D
authors.lastname: Shabaneh
authors.forename: Cathrine
authors.initials: C
authors.lastname: Bohnstedt
authors.forename: Arja
authors.initials: A
authors.lastname: Harila-Saari
authors.forename: Olafur G
authors.initials: OG
authors.lastname: Jonsson
authors.forename: Jukka
authors.initials: J
authors.lastname: Kanerva
authors.forename: Anna
authors.initials: A
authors.lastname: Lindblom
authors.forename: Bendik
authors.initials: B
authors.lastname: Lund
authors.forename: Elisabeth W
authors.initials: EW
authors.lastname: Andersen
authors.forename: Kjeld
authors.initials: K
authors.lastname: Schmiegelow
mesh_terms: D000284:Administration, Oral; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D045363:Pneumocystis carinii; D011020:Pneumonia, Pneumocystis / Q000209:etiology / Q000401:mortality* / Q000517:prevention & control*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage*
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D015122:Mercaptopurine; D008727:Methotrexate