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
Company name No support from Pharmaceutical companies at this stage Disclosures of: Hélène Schoemans Research support Employee Consultant Stockholder Speakers bureau Advisory board Other
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)
02-12 ALL 09-13 Full Sib Allo 02-14 Start Prograft taper 03-14 Further Prograft taper 04-14 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.
D230 Pulmonary Function Tests SPIROMETRIE Pred. Meas. %Pred. ----------- ----- ----- ------ FVC (L) 5.14 4.66 91 FEV1 (L) 4.35 3.93 90 FEV1/FVC (%) 82.74 84.00 PEF (L/sec) 9.90 9.57 97 FEF 25% (L/sec) 8.41 8.00 95 FEF 50% (L/sec) 5.55 4.32 78 FEF 75% (L/sec) 2.60 1.93 74 FEF 25-75%(L/sec) 5.04 3.95 78 MIF 50% (L/sec) 5.54 ingebracht op: 27-03-2013 15:03 ADEMWEERSTAND BOX Pred. Meas. %Pred. ------------- ----- ----- ------ Raw (kpa/l/s) 0.22 0.19 86 sgaw (1/(kPa*s)) 0.85 1.21 142 ingebracht op: 27-03-2013 15:03 LONGV. PLETHYSMOGR. Pred. Meas. %Pred. ------------------- ----- ----- ------ VC (L) 5.39 4.66* 87 RV (Pleth) (L) 1.62 2.16 133 TGV (Pleth) (L) 3.26 3.82 117 TLC (Pleth) (L) 6.98 6.82 98 ingebracht op: 27-03-2013 15:03 T x T x
D230 Chest Xray bilateral hazy infiltrates
D230 High resolution CT lung bilateral patchy infiltrates
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
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
D244 Rx tho
D256 High Resolution CT Intubation necessary on D275
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
D276 High Resolution CT
D279 passed away
Autopsy lung Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
Snap Frozen in liquid Nitrogen Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
Frozen Lung High Resolution CT Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
Frozen Lung Reconstructed 3D image Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
Frozen sections Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
Micro CT OB lesion Courtesy Dr Stijn Verleden, UZLEUVEN, Pneumology
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;199:581-587.
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
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?)
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