高剂量甲氨蝶呤：费城B细胞阳性急性淋巴细胞白血病患者的治疗经验

AvinashKhadela , BhavinVyas , ShrikantJoshi
苏拉特乌卡塔萨迪亚大学马利巴药学院药理学和药学实践系

摘要

大剂量甲氨蝶呤(HDMTX)在急性淋巴细胞白血病(ALL)的治疗中越来越重要。其疗效和毒性取决于剂量强度、给药途径和输注时间。HDMTX毒性可以通过持续监测尿液pH值和适当的支持性护理(过度水合、碱化剂和亚叶酸解救)来控制。一名患有B细胞Ph+ALL的患者继续使用Berlin-Frankfurt-Münster-90方案，并通过静脉输注生理盐水超过6小时给予甲氨蝶呤8g/周期。他在接受第一个化疗周期后出现白细胞减少和严重贫血，皮下注射非格司亭300mcgOD5天和1品脱红细胞。第三个周期后，患者出现粘膜炎，用亚叶酸和局麻药治疗;并继续化疗。总之，持续监测患者的尿液pH值，并在提供足够的支持性护理时很好地耐受HDMTX。

关键词

急性淋巴细胞白血病;大剂量甲氨蝶呤;亚叶酸

参考

[1]GreenMR,ChamberlainMC.Renaldysfunctionduringandafterhigh‑dosemethotrexate.CancerChemotherPharmacol2009;63:599‑604.

[2]WidemannBC,AdamsonPC.Understandingandmanagingmethotrexatenephrotoxicity.Oncologist2006;11:694‑703.

[3]WallingJ.Frommethotrexatetopemetrexedandbeyond.Areviewofthepharmacodynamicandclinicalpropertiesofantifolates.InvestNewDrugs2006;24:37‑77.

[4]GökbugetN,HoelzerD.High‑dosemethotrexateinthetreatmentofadultacutelymphoblasticleukemia.AnnHematol1996;72:194‑201.

[5]KintzelPE,CampbellAD,YostKJ,BrinkerBT,ArradazaNV,FrobishD,etal.Reducedtimeforurinaryalkalinizationbeforehigh‑dosemethotrexatewithpreadmissionoralbicarbonate.JOncolPharmPract2012;18:239‑44.

[6]VonHoffDD,PentaJS,HelmanLJ,SlavikM.Incidenceofdrug‑relateddeathssecondarytohigh‑dosemethotrexateandcitrovorumfactoradministration.CancerTreatRep1977;61:745‑8.

[7]SandTE,JacobsenS.EffectofurinepHandflowonrenalclearanceofmethotrexate.EurJClinPharmacol1981;19:453‑6.

[8]StollerRG,HandeKR,JacobsSA,RosenbergSA,ChabnerBA.Useofplasmapharmacokineticstopredictandpreventmethotrexatetoxicity.NEnglJMed1977;297:630‑4.

[9]ChangJE,MedlinSC,KahlBS,LongoWL,WilliamsEC,LionbergerJ,etal.AugmentedandstandardBerlin‑Frankfurt‑Munsterchemotherapyfortreatmentofadultacutelymphoblasticleukemia.LeukLymphoma2008;49:2298‑307.

[10]KhadelaA,VyasB,JoshiS.Roleofglucarpidaseforintoxicationofhighdosemethotrexatetoxicity.JPharmApplSci2019;6:110.

[11]HowardSC,McCormickJ,PuiCH,BuddingtonRK,HarveyRD.Preventingandmanagingtoxicitiesofhigh‑dosemethotrexate.Oncologist2016;21:1471‑82.

[12]DolaiTK,PanigrahiA,DeR,KumarM,MandalP,BagchiB,etal.OutcomeofALL‑BFM(Berlin‑Frankfurt‑Münster)90Protocolinchildhoodacutelymphoblasticleukemiainaresourceconstraintsetting.Washington,DC:AmericanSocietyofHematology;2015.

[13]FerdousiSA,AkhterA,NaharK,IslamA.Highdosemethotrexateandleucovorinrescuetherapyinchildhoodmalignancies:Experienceinresource‑limitedcountry.BangladeshJChildHealth2017;41:15‑23.

[14]BendallLJ,BradstockKF.G‑CSF:Fromgranulopoieticstimulanttobonemarrowstemcellmobilizingagent.CytokineGrowthFactorRev2014;25:355‑67.