Masahito Tsurusawa1, Masahiko Gosho1, Tetsuya Mori2, Tetsuo Mitsui3, Shosuke Sunami4, Ryoji Kobayashi5, Reiji Fukano6, Fumiko Tanaka7, Naoto Fujita8, Hiroko Inada9, Katsuyoshi Koh10, Tetsuya Takimoto11, Akiko Saito12, Junichiro Fujimoto11, Atsuko Nakazawa13, Keizo Horibe12. 1. The Advanced Medical Research Center, Aichi Medical University, Aichi, Japan. 2. Division of Pediatric Oncology, National Center for Child Health and Development, Tokyo, Japan. 3. Department of Pediatrics, Yamagata University Hospital, Yamagata, Japan. 4. Department of Pediatrics, Japanese Red Cross Narita Hospital, Chiba, Japan. 5. Department of Pediatrics, Sapporo Hokuyu Hospital, Sapporo, Japan. 6. Department of Pediatrics, Kushu Cancer Center, Fukuoka, Japan. 7. Department of Pediatrics, Saiseikai Yokohama Nanbu Hospital, Kanagawa, Japan. 8. Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Japan. 9. Department of Pediatrics, Kurume University Hospital, Kurume, Japan. 10. Department of Hematology-Oncology, Saitama Children's Medical Center, Saitama, Japan. 11. Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan. 12. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. 13. Department of Pathology, National Center for Child Health and Development, Tokyo, Japan.
Abstract
BACKGROUND: Plasma monitoring of Methotrexate (MTX) levels is a standard approach to predict MTX-related toxicities in a high-dose (HD) MTX monotherapy for childhood acute lymphoblastic leukemia. However, it is uncertain whether plasma MTX levels can predict MTX-related toxicity in the HDMTX plus additional chemotherapy for childhood B-cell nonHodgkin lymphoma (B-NHL). PROCEDURES: To statistically analyze the relationship between MTX pharmacokinetic parameters and MTX-related toxicities, we collected data from patients with delayed MTX elimination (≥1 µM at 48 hr and/or ≥0.5 µM at 72 hr) in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) BNHL 03 study. Blood MTX levels were measured at 24, 48, and 72 hr after 3 or 5 g/m2 HD-MTX administration for 24 hr. RESULTS: Three hundred and four patients received 2-4 courses of the HDMTX plus additional chemotherapy, and delayed MTX elimination was observed in 165 courses of 127 patients. In those, nephrotoxicity was significantly correlated with plasma MTX levels for each patient (P = 0.03), and also for each course (P = 0.009), but no other toxicities were correlated. Another analysis according to HDMTX courses showed no significant correlation between the first high plasma MTX levels and subsequent MTX levels in later course. It also showed that incidence of liver and gastrointestinal toxicities was most frequent in the first HDMTX course, and then sharply decreased in later courses (P < 0.001). CONCLUSIONS: Our results suggest that plasma MTX level is not a reliable predictor for adverse events except for nephrotoxicity in multiple HDMTX therapy courses in childhood B-NHL. Pediatr Blood Cancer 2015;62:279-284.
BACKGROUND: Plasma monitoring of Methotrexate (MTX) levels is a standard approach to predict MTX-related toxicities in a high-dose (HD) MTX monotherapy for childhood acute lymphoblastic leukemia. However, it is uncertain whether plasma MTX levels can predict MTX-related toxicity in the HDMTX plus additional chemotherapy for childhood B-cell nonHodgkin lymphoma (B-NHL). PROCEDURES: To statistically analyze the relationship between MTX pharmacokinetic parameters and MTX-related toxicities, we collected data from patients with delayed MTX elimination (≥1 µM at 48 hr and/or ≥0.5 µM at 72 hr) in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) BNHL 03 study. Blood MTX levels were measured at 24, 48, and 72 hr after 3 or 5 g/m2 HD-MTX administration for 24 hr. RESULTS: Three hundred and four patients received 2-4 courses of the HDMTX plus additional chemotherapy, and delayed MTX elimination was observed in 165 courses of 127 patients. In those, nephrotoxicity was significantly correlated with plasma MTX levels for each patient (P = 0.03), and also for each course (P = 0.009), but no other toxicities were correlated. Another analysis according to HDMTX courses showed no significant correlation between the first high plasma MTX levels and subsequent MTX levels in later course. It also showed that incidence of liver and gastrointestinal toxicities was most frequent in the first HDMTX course, and then sharply decreased in later courses (P < 0.001). CONCLUSIONS: Our results suggest that plasma MTX level is not a reliable predictor for adverse events except for nephrotoxicity in multiple HDMTX therapy courses in childhood B-NHL. Pediatr Blood Cancer 2015;62:279-284.
Authors: Marc Ghannoum; Darren M Roberts; David S Goldfarb; Jesper Heldrup; Kurt Anseeuw; Tais F Galvao; Thomas D Nolin; Robert S Hoffman; Valery Lavergne; Paul Meyers; Sophie Gosselin; Tudor Botnaru; Karine Mardini; David M Wood Journal: Clin J Am Soc Nephrol Date: 2022-03-02 Impact factor: 10.614
Authors: Nur Melani Sari; Lulu E Rakhmilla; Muhammad Hasan Bashari; Zulfan Zazuli; Nur Suryawan; Susi Susanah; Lelani Reniarti; Harry Raspati; Eddy Supriyadi; Gertjan J L Kaspers; Ponpon Idjradinata Journal: Asian Pac J Cancer Prev Date: 2021-07-01