Improving the safety of high-dose methotrexate for children with hematologic cancers in settings without access to MTX levels using extended hydration and additional leucovorin.
Pediatr Blood Cancer
; 65(12): e27241, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-29768710
ABSTRACT
BACKGROUND:
A lack of access to methotrexate levels is common in low- and middle-income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high-dose methotrexate (HD-MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH.METHODS:
The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B-cell acute lymphoblastic leukemia (ALL) or with T-cell ALL or non-Hodgkin lymphoma (T-NHL) were administered 3 and 5 gm/m2 of MTX (24 hr infusion), respectively. Six doses of leucovorin (15 mg/m2 /dose), instead of recommended three (for optimally reduced levels) at standard timing (42 hr from start of HD-MTX) were administered. Hydration (125 ml/m2 /hr) was continued for 72 hr, instead of the recommended 30 hr. Hydration fluid consisted of 0.45% sodium chloride, 5% dextrose, 7.5% sodium bicarbonate (50 mmol/l) and potassium chloride (20 mmol/l). Serum creatinine and urine pH were measured at baseline, 24 and 48 hr. The volume of hydration was increased (200 ml/m2 /hr) for a serum creatinine > 1.25 times the baseline.RESULTS:
The study included 100 cycles of HD-MTX in 53 patients B-ALL 25 patients (51 cycles), T-ALL 16 patients (28 cycles), T-NHL 10 patients (18 cycles), and relapsed ALL 2 patients (3 cycles). The mean age was 6.8 ± 3.2 years. Patients were underweight in 15 (15%) cycles. Patients in 23% of cycles had a rise in creatinine to >1.25 times the baseline. Toxicities (NCI CTCAE v4.0) included mucositis (32%), diarrhoea (10%), and febrile neutropenia (9%). One patient died from dengue shock syndrome.CONCLUSIONS:
It is safe to administer 3 or 5 gm/m2 of MTX (24 hr infusion) without measuring MTX levels, with extended hydration, additional doses of leucovorin, and monitoring of serum creatinine and urine pH.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metotrexato
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Leucovorina
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Neoplasias Hematológicas
Tipo de estudo:
Observational_studies
Limite:
Adolescent
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Child
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Child, preschool
/
Female
/
Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article