[Study on elimination delay in high dose methotrexate therapy in childhood acute lymphoblastic leukemia].
OBJECTIVE
To observe the incidence of elimination delay in high dose methotrexate (HDMTX) therapy, its side effects and influence to next course of chemotherapy and analyze the relationship between the dosage, the duration of MTX infusion and the morbidity of the elimination delay.


METHODS
A total of 121 childhood acute lymphoblastic leukemia (ALL) (497 infusions of HDMTX) were analysed in this study. The elimination delay rate and the adverse effects in different dose groups (3 g/m2 vs 5 g/m2) and different infusion duration groups (7 h vs 24 h) were compared. The adverse effect evaluation was based on the World Health Organization (WHO) Toxicity Grading Criteria. The rescue dosages of calcium folinate (CF) among these groups were compared through CF/MTX index.


RESULTS
The overall morbidity of elimination delay was 12.1% with a relative risk of 30.6% for the first time. The relative risk for the second time of occurrence was increased to 45.9% (P < 0.01) and it was not significantly increased for the third time (35.3%). Children with elimination delay had lower platelet count (P < 0.01) and higher CF rescue dosage (P < 0.01), while the damage of oral mucous membrane was more severe (P < 0.05) and the next course of chemotherapy would be postponed for a median of 4 days in 3 g group. There was no significant difference in elimination delay rates between 3 g and 5 g groups (12.1% vs 12.0%, P > 0.05), and between 7 h and 24 h MTX infusion groups (13.6% vs 11.9%, P > 0.05). The only side effect occurred in 5 g group was gastrointestinal morbidity. The CF/MTX index of 5 g group without elimination delay was less than that of 3 g group (P < 0.01).


CONCLUSIONS
Elimination delay in HDMTX therapy accompanies the suppression of bone marrow and damage of oral mucous membrane, which need more CF rescues and will postpone the following course of chemotherapy. Elimination delay is not associated with the duration of the infusion and the dosage of MTX within the range of 3 approximately 5 g/m2 but there are individual differences.
Xu
Wei-qun
WQ
Division of Hematology and Oncology, Children's Hospital of Zhejiang University, School of Medicine, Hangzhou 310003, China.
Tang
Yong-min
YM
Fang
Cheng-qing
CQ
Song
Hua
H
Shi
Shu-wen
SW
Yang
Shi-long
SL
Ren
Ding-tai
DT
Shen
Hong-qiang
HQ
Qian
Bai-qin
BQ
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate