Solitary serum methotrexate level 36 hours post high-dose methotrexate: A safe, efficacious, and cost-effective strategy to monitor methotrexate toxicities in childhood leukemia in resource-limited centers.
Pediatr Blood Cancer
; 67(7): e28387, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32400952
ABSTRACT
BACKGROUND:
The standard practice during high-dose methotrexate (HD-MTX) in acute lymphoblastic leukemia (ALL) to mitigate toxicity is to serially monitor levels till serum MTX < 0.01 µmol/L. Most resource-limited centers lack in-house access to MTX levels, and therefore repeated monitoring is costly and cumbersome. We studied the efficacy and safety of "solitary 36 hours post HD-MTX levels (MTX36 )." PROCEDURE This prospective observational study consecutively enrolled children with ALL receiving HD-MTX. Cycles with unavailable MTX36 and MTX36 > 10 µmol/L were excluded. HD-MTX was administered over 24 hours (BFM-2009 protocol) with 12 hours of prehydration. MTX36 were performed at other centers. Leucovorin was given in six hourly doses 36 hours post HD-MTX. Hydration was continued until the last dose of leucovorin. MTX toxicities, including change of creatinine from baseline at 36 hours (∆Cr36 ), were noted. Two groups depending on MTX36 (≤1 µmol/L vs > 1 µmol/L) received six versus eight doses of leucovorin, and toxicities were compared.RESULTS:
Twenty-nine children with median age five years (1-11) who received 100 HD-MTX cycles with a median MTX dose of 3 g/m2 (2-5) were analyzed. The median MTX36 level was 1.165 µmol/L (0.1-7.32). Toxicities of HD-MTX (CTCAE-4.0) transaminitis-22%; creatinine elevation ≥ 1.25 times baseline-24%; cytopenias-16%; mucositis-17%; acute kidney injury (AKI)-6%. All toxicities were ≤CTCAE grade 3. Creatinine elevation, AKI, and mucositis were significantly higher in the group with higher MTX36 . There was no correlation (r = 0.3) between ∆Cr36 and MTX36 . MTX36 was thrice more economical than the standard protocol.CONCLUSION:
MTX36 is a potential cost-effective, efficacious, and safe limited sample strategy to monitor HD-MTX, particularly in centers where in-house MTX levels are unavailable.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metotrexato
/
Análise Custo-Benefício
/
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Antimetabólitos Antineoplásicos
Tipo de estudo:
Etiology_studies
/
Guideline
/
Health_economic_evaluation
/
Observational_studies
/
Prognostic_studies
Limite:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article