Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia
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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. / Levinsen, Mette; Shabaneh, Diana; Bohnstedt, Cathrine; Harila-Saari, Arja; Jonsson, Olafur G.; Kanerva, Jukka; Lindblom, Anna; Lund, Bendik; Andersen, Elisabeth Anne Wreford; Schmiegelow, Kjeld.
In: European Journal of Haematology, Vol. 88, No. 1, 01.2012, p. 78-86.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia
AU - Levinsen, Mette
AU - Shabaneh, Diana
AU - Bohnstedt, Cathrine
AU - Harila-Saari, Arja
AU - Jonsson, Olafur G.
AU - Kanerva, Jukka
AU - Lindblom, Anna
AU - Lund, Bendik
AU - Andersen, Elisabeth Anne Wreford
AU - Schmiegelow, Kjeld
PY - 2012/1
Y1 - 2012/1
N2 - 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
AB - 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
U2 - 10.1111/j.1600-0609.2011.01695.x
DO - 10.1111/j.1600-0609.2011.01695.x
M3 - Journal article
C2 - 21854453
VL - 88
SP - 78
EP - 86
JO - European Journal of Haematology
JF - European Journal of Haematology
SN - 0902-4441
IS - 1
ER -
ID: 38347607