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

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 2-7d/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 7months 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. 63.9mg/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.

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 2-7d/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 7months 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. 63.9mg/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.

U2 - 10.1111/j.1600-0609.2011.01695.x

DO - 10.1111/j.1600-0609.2011.01695.x

M3 - Journal article

C2 - 21854453

SN - 0902-4441

VL - 88

SP - 78

EP - 86

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 1

ER -