MuktaAroraMD MSCIBMTR - PDF document

1 MuktaAroraMD MSCIBMTR Transplant Events -8 -1 0 1mo 3mo 6mo Conditioning TransplantMucositisOrgan toxicity (VOD)Acute GVHD Chronic GVHD InfectionsBacterial CMVVaricellaFungus Engraftment Dermatitis Hepatitis E

nteritisAcute GVHD Chronic GVHD Skin: Lichen planus,Hyper/ hypo pigmentation, ichthyosis, onychodystrophy, morphea,scleroderma, hair changes.Oral: sicca, atrophy, lichenoid, HyperkeratosisGI: wasting, dysphagia, odynophagia, stricturesEye: keratoconjunctivitissiccaLungs: BronchiolitisobliteransOthers: myofascial, ge

nital 4 nonmyeloablativetransplants Related donorUnrelated donor Incidence of chronic Graft versus Host disease after non myeloablativetransplants Related donor Unrelated donorMielcareket alLeukLymphoma.2005 Sep;46(9):1251-60. l T cell depletion Cumulative incidence of acute and chron

ic GVHD after T cell depleted URD transplantPavleticet al. Blood.2005 Nov 1;106(9):3308-13. 6 Generalized maculo-papularrash Apoptotic crypt cells on GI histologySkin biopsy showing interface dermatitis •Grade I (skin stage I or II): Topical steroids•Moderate to Severe: MethylprednisoneAge, higher grade, unrelated do

nor.Factors associated with mortality53%Survival@ 1 year20%Related donor, GVHD prophylaxis other than MTxalone35%28 d % CRFactors associated with CR/PR13%Grade III/IV60%Grade II27%Grade I443 BBMT 2002,MacMillan et al. 7 Case 1 contd.Improved rash and diarrhea, but hospitalized with SOB. CT Scan suggestive of fungal inf

ection. Started on Voriconazole. Steroid taper started.Day 70: Readmitted with worsening rash and diarrhea. Stool cultures negative. Stool volume: 1.5 litres/ dayDx: Flare of graft versus host diseaseRx: Steroid boluses •Day 80: Rash minimally improved, no improvement in diarrhea.•Dx: Steroid refractory disease•Rx: ATG

Day 100: Diarrhea and rash improved, steroid taper restarted Secondary treatment of Acute GVHD•Choosing options:PhotopharesisAlemtuzumabMonoclonal anti T & B cell AbsDaclizumab, VisilizumabMonoclonal anti T cell AbsDenileukinDiftitoxAnti T cell fusion proteinsSirolimus, TacrolimusMacrolidesMMFPentostatinAntimetabolites

InfliximabEtanerceptAnti cytokine agentsATGPolyclonal anti T cell Abs 9 Case 2 contd.•Day 150: mouth pain, anorexia, weight loss, skin shows patchy areas of hypopigmentationand hyperpigmentation.•Oral exam: lichenoidchanges.•Platelet count: 52,000/µl•Lip biopsy: diagnostic of CGVHD•Dx: Extensive CGVHD•Rx: Steroids + CS

A, topical steroids for skin involvement Skin involvement with CGVHD Sclerotic CGVHD of the lips and mucosa with restricted mouth opening 11 Case 2 contd.•Day 180: admitted with fever and SOB. •CT chest: patchy b/linterstitial opacities•Bronchoscopy: CMV pneumonia•Blood culture : + VRE•Rx: antibiotics + Ganciclovir Inf

ections complicating CGVHD Case 2 contd.•Day 200: continued weight loss, oral pain, now having difficulty opening mouth. Also complaining of difficulty swallowing.•Exam: Oral changes: worsening, restriction in mouth opening, Upper GI endoscopyrevealed esophageal stricture.•Dx: Progressive CGVHD•Rx: Methylprednisonebolu

ses, increased dose of oral steroids, continued CSA, added MMF 13 62 years old woman with Ph+ ALLCytoxan/ fludarabine/ TBI Double umbilical cord transplantGVHD prophylaxis: CSA + MMFDay 28: Diffuse rash + diarrhea Dx: AGVDH skin + + +, GI + + Rx: High dose methylprednisone Case 3 contd.HUS with CSA, hence MMF was conti

nued. Improved rash, but hospitalized with SOB. CT Scan suggestive of fungal infection. Rash and diarrhea improved. Started on Voriconazole. Steroid taper started.Day 84: Increased rash, nausea, anorexia, oral pain with lichenoidchanges in oral mucosa, decreased platelet count. Dx: Oral biopsy positive for chronic graf

t versus Rx: Treated with steroid boluses x 5 days. Oral daily prednisone increased to 1mg/kg/day. Case 3 contd.Day 100: Admitted with fever and failure to thrive. Blood culture positive for VRE, chest CT with worsening pulmonary nodules.Rx: Started mycofungin+ linezolid. Started TPN. Added Tacrolimus. Requringnarcotic

s for oral painDay 120: Elevated LFTs. Voriconazoleheld. LFTscontinued to rise.Admitted with fever + cough and SOB.Rx: Bronchoscopy+ CMV pneumonia. Started ganciclovirDay 130: Elevated LFTs, coagulopathy, worsening lung infilteratesRx: Bronchoscopy: diffuse alveolar hemorrhage. Intubated. Started high dose steroids.Day

140: Blood culture positive for stenotrophomonas, patient became progressively hypotensiveand died. 15 Otherfeaturesof chronic GVHD define the rare, controversial, or nonspecific features of chronic used to establish the diagnosis of chronic GVHD. signs and symptoms of chronic GVHD refer to manifestations found in bot

h chronic and acute GVHD Xerostomia, Mucocele, Mucosal atrophy, PseudomembranesUlcersLichen-type featuresHyperkeratoticplaquesRestriction of mouth openingMouthNew onset of scarring or nonscarringscalp alopecia. Scaling, papulosquamouslesionsScalp, Dystrophy. Longitudinal ridging, splitting, or brittle nails. Onycholys

isPterygiumunguis. Nail lossDepigmentationPoikilodermaLichen planus/ Sclerotic features/ Morphea-like featuresDistinctive features Distinctive featuresMyositisor polymyositisFasciitis, joint stiffness or contracturesMuscles, BO diagnosed with PFTsand radiologyBO diagnosed with lung biopsyEsophageal web, strictures or s

tenosisin the esophagusErosions, Fissures, UlcersLichen planus-like featuresVaginal scarring or stenosisGenitaliaNew onset dry, gritty, or painful eyes, CicatricialconjunctivitisKeratoconjunctivitissicca, punctatekeratopathyEyes 17 •Important for accurate and adequate data collection for both acute and chronic GVHD.•Ac

curate and complete data are essential on organ involvement. 19 Conclusions•More randomized trials are needed to build evidence based approach to management of these diseases.•BMT CTN Protocol 0302: Randomized phase II for primary treatment of AGVHD with glucocorticoidsand (MMF, DenileukinDiftitox, Etanerceptand Pentos