The use of extracorporeal photochemotherapy (ECP) for the treatment of chronic and acute GvHD. Experience of centre CIC 725 EBMT

摘要

HematopoieticStemCellTransplantation(HSCT)isthegoldstandardinthetreatmentofmanydiseasesandthemanyexperiencesofitsapplicationarespreadingnow.Unfortunately,graftversushostdisease(GVHD)stillremainstheleadingcauseofmorbidityandmortalityofpatientsafterHSCTwhohaverecoveredfromtheunderlyingdisease.TheapplicationofsystemicimmunesuppressiontotreatGVHDoftenleadstosignificantmortalityfrominfectiouscomplications.Therefore,aneffectiveandnon-toxicmethodofselectiveimmunemodulationwithouttotalimmunesuppression,suchasextracorporealphotochemotherapy,isfindingwiderapplicationaftertransplantation.Methods:Fourteenpost-allogeneicHSCTpatientsweretreatedwith78proceduresofextracorporealphotochemotherapybyana€?opensystema€?(off-line)method.ThecollectionofcellswasperformedbyaCobaSpectracellseparator(GambroMedical)andexposedtoaMacogenicirradiationdevice(Macopharma)withtheadditionof0.002%metoxypsoralen(8-MOP)tothetargetconcentrationof200ng/mlatdoseof2.0a€“2.5J/cm2.WeanalyzedourdataofpatientswithacuteandchronicGVHDtreatedwithECPinourcenterfromDecember2009untilJune2010.Themedianagewas30.5years.Fivepatientswerechildrenandadolescentsunder18years,including3ptsunder14years.Menandwomenweredivided50/50%.Thepatient'sdiagnosiswasasfollows:AML,5,ALL,3,CML,4,CLL,1,andMDS,1.Results:In10patientswithsteroid-refractorychronicGVHDwithskinandmucousinvolvements,ECPwasperformedattherateof2a€“4procedurespermonth(2consecutivedaysevery2a€“4weeks),dependingontheseverityofclinicalmanifestations.In2caseswenotedtheinvolvementofthelungswithaclinicallysignificantreductionintheresiduallungcapacityandexpiratorypeakflowrateasthedevelopmentofbronchiolitisobliteranssyndrome.Onepatientexperiencedliverinvolvement.Thenumberofirradiationsvariedfrom2to12,or5.9perpatientonaverage.AllpatientsrespondedtoECPtherapy.7patients(70%)hadapartialresponse,andin3(30%)casesastabilizationofdiseaseenabledthepossibilityofreductioninsteroiddoseto50%orcompletetermination.Nobodydiedduringtreatmentinthisgroup.4patientswithacuteGVHDinvolvingtheskin,gastrointestinaltract,andliverreceivedfrom1to2ECPprocedures.Byscheduleoneprocedurewasperformedweeklyuntilaclinicalresultwithsteroidandtotalimmunesuppressiontherapy.ThebesteffectwasachievedinallpatientswithGVHDwithskinandmucousinvolvement.OneboywithacuteGVHDoftheskinandeyeshadcompleteregressionofclinicalmanifestationsandthereductionofsteroidsduringtheweek.TheuseofECPinacuteGVHDoftheintestinalandliverhasnotledtoanyreliableeffects.BothpatientsdiedfrommultipleorganfailurewithclinicalsignsofintestinalGVHDgrade3a€“4.Statisticaldataoflymphocytespopulationsandcytokinelevelinourlimitedgroupofpatientsshowednostatisticallysignificantassociations.Allproceduresweresafeforpatientswithlaboratoryresultsandbacteriologicalcontrol.Conclusion:OurpreliminaryexperiencedemonstratesthatECPissafeandefficaciousmethodinGVHDtreatment.