Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate ⁄ 6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia

Mette Levinsen, Diana Shabaneh, Cathrine Bohnstedt, Arja Harila-Saari, Olafur G. Johnsson, Jukka Kanerva, Anna Lindblom, Bendik Lund, Elisabeth Wreford Andersen, Kjeld Schmiegelow

Research output: Contribution to journalJournal articleResearch

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 ⁄SMX2–7) and 287 patients never received TMP⁄SMX (TMP ⁄SMXnever). Ten patients (all TMP⁄SMXnever) developed PCP, eight of which occurred within 7 months from the start of maintenance therapy. The TMP⁄SMX2–7 group received lower oral 6MP doses than TMP⁄SMXnever patients (50.6 vs. 63.9 mg⁄m2 ⁄ d; P < 0.001) but had lower absolute neutrophil counts (ANC) (median 1.7 vs. 2.0 · 109 ⁄ 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⁄SMX2–7 patients (P = 0.40) but did for TMP⁄SMXnever patients (P = 0.02). The difference in the effect on EFS between TMP⁄SMX2–7 and TMP⁄SMXnever patients was not significant (P = 0.46). EFS did not differ between TMP⁄SMX2–7 and TMP⁄SMXnever 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.
Original languageEnglish
JournalEuropean Journal of Haematology
Volume88
Issue number1
Pages (from-to)78-86
Number of pages9
ISSN0902-4441
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • childhood acute lymphoblastic leukemia
  • treatment
  • infection

Fingerprint Dive into the research topics of 'Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate ⁄ 6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia'. Together they form a unique fingerprint.

Cite this