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Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6‐mercaptopurine dosing but not event‐free survival for childhood acute lymphoblastic leukemia
Author(s) -
Levinsen Mette,
Shabaneh Diana,
Bohnstedt Cathrine,
HarilaSaari Arja,
Jonsson Olafur G.,
Kanerva Jukka,
Lindblom Anna,
Lund Bendik,
Andersen Elisabeth W.,
Schmiegelow Kjeld
Publication year - 2012
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2011.01695.x
Subject(s) - medicine , dosing , methotrexate , mercaptopurine , pneumonia , lymphoblastic leukemia , pneumocystis pneumonia , acute lymphocytic leukemia , asparaginase , leukemia , intensive care medicine , pediatrics , immunology , pneumocystis jirovecii
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.