A CASE OF UNFORTUNATE
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1 A CASE OF UNFORTUNATE TAPER Hélène Schoemans, MD University Hospitals Leuven, Belgium EBMT Complications and Quality of Life Working Party Educational Course Warsaw, October 24 th 2014
2 Company name No support from Pharmaceutical companies at this stage Disclosures of: Hélène Schoemans Research support Employee Consultant Stockholder Speakers bureau Advisory board Other
3 The case of C.W. 25j, complex karyotype T-ALL (March 2012) Chemotherapy CR Full (Cy-TBI) allo Tx with sibling sister (Sept 2013) PRES with epilepsy on cyclosporine tacrolimus D50: CR, full donor, no GVHD D100: CR, full donor, no GVHD D180: CR, full donor, no GVHD Tacrolimus taper started per protocol D180 (trough level 7) Further taper one month later (trough level 3)
4 02-12 ALL Full Sib Allo Start Prograft taper Further Prograft taper Shortness of breath - D215 admitted at the emergency Dpt with chest pain Rx tho neg, ECG neg, labo neg. pericarditis? R/Aspirine - D230 admitted for shortness of breath and dry cough.
5 D230 Pulmonary Function Tests SPIROMETRIE Pred. Meas. %Pred FVC (L) FEV1 (L) FEV1/FVC (%) PEF (L/sec) FEF 25% (L/sec) FEF 50% (L/sec) FEF 75% (L/sec) FEF 25-75%(L/sec) MIF 50% (L/sec) 5.54 ingebracht op: :03 ADEMWEERSTAND BOX Pred. Meas. %Pred Raw (kpa/l/s) sgaw (1/(kPa*s)) ingebracht op: :03 LONGV. PLETHYSMOGR. Pred. Meas. %Pred VC (L) * 87 RV (Pleth) (L) TGV (Pleth) (L) TLC (Pleth) (L) ingebracht op: :03 T x T x
6 D230 Chest Xray bilateral hazy infiltrates
7 D230 High resolution CT lung bilateral patchy infiltrates
8 D233 - Bonchus Aspiration Culture negative for all bacteria and fungi, Aspergillus Antigen negative, Auramine negative, Adenovirus negative Influenzavirus A PCR Influenzavirus B PCR Parainfluenza type 1 PCR Parainfluenza type 2 PCR Parainfluenza type 3 PCR Parainfluenza type 4 PCR RSV PCR hmpv PCR Mycoplasma pneumoniae PCR Pneumocystis jiroveci PCR Legionella pneumophila PCR Herpes simplex virus 1 PCR Herpes simplex virus 2 PCR Varicella-zostervirus PCR Cytomegalovirus PCR Toxoplasma PCR
9 8 months post Tx, during Tacrolimus taper Shortness of breath with cough Normal PFT, but diffuse infiltrations on Chest Xray and HRCT Negative bronchus aspirate No other GVHD symptoms D233 - Start Meropenem-(Acyclovir-Eusaprim) D237 Start Cortisone 1mg/kg + Azithro D245 Association Caspofungine DETERIORATION
10 D244 Rx tho
11 D256 High Resolution CT Intubation necessary on D275
12 D275 bronchus aspirate Bacterial/fungus Culture negative Aspergillus Antigen 1,7 Influenzavirus A PCR Influenzavirus B PCR Pneumocystis jiroveci PCR Legionella pneumophila PCR Herpes simplex virus 1 PCR Herpes simplex virus 2 PCR strongly positive Peripheral biopsies: non contributive
13 D276 High Resolution CT
14 D279 passed away
15 Autopsy lung Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
16 Snap Frozen in liquid Nitrogen Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
17 Frozen Lung High Resolution CT Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
18 Frozen Lung Reconstructed 3D image Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
19 Frozen sections Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
20 Micro CT OB lesion Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
21 GVHD of the lungs Fibrosis RAS Restrictive Allograft Syndrome Pulmonary infiltrates Pleural disease Fibrosis Restriction COOP BOOP Obstruction BOS Bronchiolitis Obliterans Syndrome Peribronchial proliferation between epithelium and smooth muscle Airtrapping Obstruction Peribronchial fibrosis Epithelial destruction Lymphocyte infiltrations Traction bronchiectasis AJR 2012;199:
22 Clinical PFT Radiology Refining the Fibrotic Phenotype AFOP Acute Fibrinoid Organizing Pneumonia Rapid decline in FEV1 leading to death Bilateral infiltrates and ground-glass change with intralobular septal thickening Nonobstructive RAS Restrictive Allograft Syndrome Stepwise deterioration in FEV1 with periods of stability Upper lobe fibrosis Histopathology Fibrin filling the alveolar spaces No interstitial infiltrate or fibrosis Various stages of DAD Extensive fibrosis of the alveolar interstitium, visceral pleural and interlobular septa Paraskeva et al, Am J Respir Crit Care Med. 2013
23 Conclusion Lung GVHD is complex and pleomophic (are NIH criteria adequate to stage it appropriately?) PFTs are important but do not always predict clinical decline Parallels can be drawn with lung Tx recipients for physiopathology Accurate diagnosis is needed to identify which patients could benefit from newer anti fibrotic therapies (Pirfenidone?)
24 In the end, it's not about how many breaths you took. In the end, it's about the moments that took your breath away. Shing Xiong
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