Effects of Trimethoprim on Leukaemic Cells <i>in Vitro</i>

Rivard, Georges E.; Momparler, Louise F.; Momparler, Richard L.

doi:10.1111/j.1365-2141.1981.tb02782.x

Cited by 6 publications

(1 citation statement)

References 13 publications

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“…TMP binds the enzyme dihydrofolate reductase in a manner analogous to MTX (19), but with less cytotoxic efficacy compared to MTX (36). Furthermore, TMP/SMX suppresses cell replication in leukemic cell lines (18, 19, 37).…”

Section: Discussionmentioning

confidence: 99%

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

Levinsen

Shabaneh

Bohnstedt

et al. 2011

European J of Haematology

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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.

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Section: Discussionmentioning

confidence: 99%

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

Levinsen

Shabaneh

Bohnstedt

et al. 2011

European J of Haematology

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Effect of trimethoprim/sulfamethoxazole prophylaxis on outcome of childhood lymphocytic leukemia a pediatric oncology group study

Eys

Berry

Crist

et al. 1987

Cancer

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The Pediatric Oncology Group (POG) undertook a prospective randomized trial using a single chemotherapy regimen with or without trimethoprim/sulfamethoxazole (TS). In a previous acute lymphocytic leukemia (ALL) study of initial therapy, investigators were free to use TS prophylaxis or not. Analysis of those data seemed to favor TS for duration of continuous complete remission. In the study reported here, of 126 randomized patients with ALL, 63 received TS. There was no effect of TS on disease-free survival after 3 years follow-up. Overall severe toxicity did not differ. However, granulocytopenia was somewhat more severe in the TS group. Hepatic toxicity, measured by enzyme elevation approached significance in the TS group versus controls. Some institutions declined randomization and treated with or without TS as a routine. Outcome and toxicities did not differ from randomized patients. There was no statistically significant effect on severe, life-threatening or fatal infection between the randomized TS versus control groups. Children not receiving TS developed varicella more often, a disease for which one would not expect TS to show a preventative effect. Pneumocystis pneumonias were not reported. The authors conclude that TS prophylaxis did not increase the continuous complete remission rate in children with ALL or decrease the incidence of infection. Toxicity is somewhat higher on TS.

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Randomized controlled trial comparing trimethoprim/sulfamethoxazole and trimethoprim for infection prophylaxis in hospitalized granulocytopenic patients

Bow¹,

Louie²,

Riben³

et al. 1984

The American Journal of Medicine

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Effects of Trimethoprim on Leukaemic Cells in Vitro

Cited by 6 publications

References 13 publications

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

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

Effect of trimethoprim/sulfamethoxazole prophylaxis on outcome of childhood lymphocytic leukemia a pediatric oncology group study

Randomized controlled trial comparing trimethoprim/sulfamethoxazole and trimethoprim for infection prophylaxis in hospitalized granulocytopenic patients

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