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      소아 급성림프모구백혈병 및 비호지킨림프종 환자에서 고용량 methotrexate 투여 후 배설지연 = Delayed Elimination After High-dose Methotrexate in Pediatric Patients with Acute Lymphoblastic Leukemia and Non-Hodgkin Lymphoma

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      https://www.riss.kr/link?id=A106260019

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      다국어 초록 (Multilingual Abstract)

      Background: High doses of methotrexate (MTX) are often used in various chemotherapy protocols to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) in children, but its delayed elimination increases the occurrence of adverse events, such as bone marrow suppression. The aim of this study was to investigate the elimination of MTX at 24 and 48 hours.
      Methods: We retrospectively analyzed electronic medical records of ALL or NHL pediatric patients who received 5 g/m2 MTX infusion over 24 hours (between June, 2012 and July, 2018) at the Yonsei University Health System, Korea. The delayed elimination of MTX concentrations was assessed with 100 or 150 μM MTX at 24 hours, and 2 or 5 μM at 48 hours. Results: Among the 85 MTX cycles administered, 23 cycles were classified in delayed elimination group, and 62 cycles showed normal elimination. At 24 hours, the delayed elimination group with MTX concentration > 100 μM showed higher percentage than group with MTX concentration < 100 μM (45.8% vs. 19.7%, p = 0.015). However, no differences were observed at 150 μM MTX (p = 0.66). At 48 hours, the delayed elimination was higher than the normal elimination at both concentration baselines (p < 0.001 at 2 μM, p = 0.024 at 5 μM).
      Conclusions: MTX concentrations greater than 100 μM show high probability of delayed elimination at 24 hours. When MTX levels are above normal, leucovorin and hydration regimens should be continued to prevent delayed elimination.
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      Background: High doses of methotrexate (MTX) are often used in various chemotherapy protocols to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) in children, but its delayed elimination increases the occurrence of adverse e...

      Background: High doses of methotrexate (MTX) are often used in various chemotherapy protocols to treat acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL) in children, but its delayed elimination increases the occurrence of adverse events, such as bone marrow suppression. The aim of this study was to investigate the elimination of MTX at 24 and 48 hours.
      Methods: We retrospectively analyzed electronic medical records of ALL or NHL pediatric patients who received 5 g/m2 MTX infusion over 24 hours (between June, 2012 and July, 2018) at the Yonsei University Health System, Korea. The delayed elimination of MTX concentrations was assessed with 100 or 150 μM MTX at 24 hours, and 2 or 5 μM at 48 hours. Results: Among the 85 MTX cycles administered, 23 cycles were classified in delayed elimination group, and 62 cycles showed normal elimination. At 24 hours, the delayed elimination group with MTX concentration > 100 μM showed higher percentage than group with MTX concentration < 100 μM (45.8% vs. 19.7%, p = 0.015). However, no differences were observed at 150 μM MTX (p = 0.66). At 48 hours, the delayed elimination was higher than the normal elimination at both concentration baselines (p < 0.001 at 2 μM, p = 0.024 at 5 μM).
      Conclusions: MTX concentrations greater than 100 μM show high probability of delayed elimination at 24 hours. When MTX levels are above normal, leucovorin and hydration regimens should be continued to prevent delayed elimination.

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      참고문헌 (Reference)

      1 Traivaree C, "The effect of intravenous hydration strategy on plasma methotrexate clearance during intravenous high-dose methotrexate administration in pediatric oncology patients" 10 : 4471-4478, 2018

      2 Santucci R, "Severe intoxication with methotrexate possibly associated with concomitant use of proton pump inhibitors" 30 (30): 963-965, 2010

      3 Tiwari P, "Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate" 32 (32): 576-584, 2015

      4 Xu W, "Retrospective study on elimination delay of methotrexate in high-dose therapy of childhood acute lymphoblastic leukemia in China" 29 (29): 688-693, 2007

      5 Howard SC, "Preventing and Managing Toxicities of High-Dose Methotrexate" 21 (21): 1471-1482, 2016

      6 Fabresse N, "Plasma 7-Hydroxymethotrexate Levels Versus Methotrexate to Predict Delayed Elimination in Children Receiving High-Dose Methotrexate" 40 (40): 76-83, 2018

      7 Bhojwani D, "Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia" 32 (32): 949-959, 2014

      8 Bielack SS, "Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial" 33 (33): 2279-2287, 2015

      9 Carlos D. Flombaum, "Management of Patients with Acute Methotrexate Nephrotoxicity with High-Dose Leucovorin" Wiley 38 (38): 714-724, 2018

      10 Yanagimachi M, "Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy" 98 (98): 702-707, 2013

      1 Traivaree C, "The effect of intravenous hydration strategy on plasma methotrexate clearance during intravenous high-dose methotrexate administration in pediatric oncology patients" 10 : 4471-4478, 2018

      2 Santucci R, "Severe intoxication with methotrexate possibly associated with concomitant use of proton pump inhibitors" 30 (30): 963-965, 2010

      3 Tiwari P, "Serum Creatinine Versus Plasma Methotrexate Levels to Predict Toxicities in Children Receiving High-dose Methotrexate" 32 (32): 576-584, 2015

      4 Xu W, "Retrospective study on elimination delay of methotrexate in high-dose therapy of childhood acute lymphoblastic leukemia in China" 29 (29): 688-693, 2007

      5 Howard SC, "Preventing and Managing Toxicities of High-Dose Methotrexate" 21 (21): 1471-1482, 2016

      6 Fabresse N, "Plasma 7-Hydroxymethotrexate Levels Versus Methotrexate to Predict Delayed Elimination in Children Receiving High-Dose Methotrexate" 40 (40): 76-83, 2018

      7 Bhojwani D, "Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia" 32 (32): 949-959, 2014

      8 Bielack SS, "Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial" 33 (33): 2279-2287, 2015

      9 Carlos D. Flombaum, "Management of Patients with Acute Methotrexate Nephrotoxicity with High-Dose Leucovorin" Wiley 38 (38): 714-724, 2018

      10 Yanagimachi M, "Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy" 98 (98): 702-707, 2013

      11 Schultz KR, "Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study" 27 (27): 5175-5181, 2009

      12 Winter SS, "Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children's Oncology Group AALL0434 Methotrexate Randomization" 36 (36): 2926-2934, 2018

      13 Reiss SN, "Hypoalbuminemia is significantly associated with increased clearance time of high dose methotrexate in patients being treated for lymphoma or leukemia" 95 (95): 2009-2015, 2016

      14 Skarby T, "High-dose methotrexate: on the relationship of methotrexate elimination time vs renal function and serum methotrexate levels in 1164 courses in 264 Swedish children with acute lymphoblastic leukaemia (ALL)" 51 (51): 311-320, 2003

      15 Wiczer T, "Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity" 22 (22): 430-436, 2016

      16 Larsen EC, "Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group Study AALL0232" 34 (34): 2380-2388, 2016

      17 Ranchon F, "Delayed methotrexate elimination: Incidence, interaction with antacid drugs, and clinical consequences?" 36 (36): 399-406, 2018

      18 Svahn T, "Delayed elimination of high-dose methotrexate and use of carboxypeptidase G2 in pediatric patients during treatment for acute lymphoblastic leukemia" 64 (64): 2017

      19 Cohen IJ, "Defining the appropriate dosage of folinic acid after highdose methotrexate for childhood acute lymphatic leukemia that will prevent neurotoxicity without rescuing malignant cells in the central nervous system" 26 (26): 156-163, 2004

      20 Mao J, "Creatinine clearance rate and serum creatinine concentration are related to delayed methotrexate elimination in children with lymphoblastic malignancies" 61 (61): 77-82, 2014

      21 Ramsey LB, "Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance" 23 (23): 52-61, 2018

      22 Csordas K, "Comparison of pharmacokinetics and toxicity after high-dose methotrexate treatments in children with acute lymphoblastic leukemia" 24 (24): 189-197, 2013

      23 Cerminara Z, "A single center retrospective analysis of a protocol for high-dose methotrexate and leucovorin rescue administration" 2017

      24 Schwartz GJ, "A simple estimate of glomerular filtration rate in full-term infants during the first year of life" 104 (104): 849-854, 1984

      25 Schwartz GJ, "A simple estimate of glomerular filtration rate in adolescent boys" 106 (106): 522-526, 1985

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      학술지 이력
      연월일 이력구분 이력상세 등재구분
      2027 평가예정 재인증평가 신청대상 (재인증)
      2021-01-01 평가 등재학술지 유지 (재인증) KCI등재
      2018-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2015-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2011-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2009-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2006-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      2005-05-10 학술지등록 한글명 : 한국임상약학회지
      외국어명 : Korean Journal of Clinical Pharmacy
      KCI등재후보
      2005-01-01 평가 등재후보 1차 PASS (등재후보1차) KCI등재후보
      2003-01-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      2016 0.18 0.18 0.17
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.17 0.15 0.432 0.02
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