Department of Geriatrics Unit of Respiratory Pathophysiology Lung function prior to stem cell transplant as a predictor of infectious and pulmonary complications and survival in adults with haematologic malignancies Scarlata Simone, Annibali Ombretta, Santangelo Simona, Chiodi Francesca, Ferraro Silvia, Tirindelli Maria Cristina, Avvisati Giuseppe, Antonelli Incalzi Raffaele Presenting Author: Simone Scarlata, MD Department of Geriatrics Unit of Respiratory Pathophysiology Area Ematologia Trapianto Cellule Staminali Medicina Trasfusionale e Terapia cellulare Campus Bio Medico University and Teaching Hospital Rome - Italy 1

BACKGROUND Autologous stem cell transplantation (ASCT) represents a standard of care for multiple myeloma patients eligible for high-dose therapy, for lymphoma patients undergoing second line treatments and in acute leukemia. Pulmonary and infective complications are a cause of morbidity and mortality after ASCT. While several reports focusing on allogenic transplantation exist (Cancer Invest 2002; 20:880-8.), the relationship between pre-transplant pulmonary function tests (PFTs) and development of post-ASCT complications and mortality is basically unknown.

BACKGROUND

BACKGROUND

BACKGROUND Biol Blood Marrow Transplant. 2015 Aug 7. pii: S1083-8791(15)00512-1

AIMS OF THE STUDY To evaluate the association between pulmonary function tests indexes obtained prior to autologus stem cell transplantation with: pulmonary complications infectious side effects mortality.

81 consecutive ASCT recipients Study design 81 consecutive ASCT recipients Spirometry Lung volumes DLCO KCO Blood gas analysis Pre-transplant PFT evaluation ASCT One –way analysis of variance Differences in PFR mean values by survival and infectious occurrence rate Kaplan-Meier curves and hazard models Relationships between post-transplant survival and infective complication’s rate Post-transplant evaluation

Results Age Years (mean; SD) 53.7 (10.3) Males (n°; %) 57/81 (70.4)   Age Years (mean; SD) 53.7 (10.3) Males (n°; %) 57/81 (70.4) Smokers (never/former/current) (n°; %) 42/17/19 (55.6/21/23.5) Deaths (n°/death rate) 30/81 (37.0) Mean Follow up time (months; SD) 24.7 (21.6) HAEMATOLOGICAL DIAGNOSIS Non Hodgkin’s Lymphoma (n°; %) 19 (23.5) Hodgkin’s Lymphoma (n°; %) 5 (6.2) Multiple Mieloma (n°; %) 55 (67.9) Acute Mieloid Leukemia (n°; %) 2 (2.5) PRE-TRANSPLANT FEATURES Response to pre-transplant treatment Partial response (n°; %) 52/81 (64.2) Complete response (n°; %) 23/81 (28.4) Stable disease (n°; %) 3/81 (3.7) Disease progression (n°; %) Patients exposed to pneumotoxic agents in pre-transplant treatment (n°; %) 39/81 (48.1) Patients with lung abnormalities at the chest CT scan (n°; %) 19/81 (23.5) POST-TRANSPLANT FEATURES Major Infective Event (n° events/%) 43/81 (53.1) Early Respiratory infections (within 100 days) 12/81 (14.8) Late Respiratory infections (more than 100 days) 8/81 (9.9)

Results RESPIRATORY FUNCTION TEST FEV1 liters (mean; SD) 3.00 (0.76)   FEV1 liters (mean; SD) 3.00 (0.76) FEV1 % of predicted (mean; SD) 97.4 (17.0) FVC liters (mean; SD) 3.80 (0.89) FVC % of predicted (mean; SD) 100 (16.4) RV % of predicted (mean; SD) 87.6 (24.9) TLC liters (mean; SD) 5.67 (1.27) TLC % of predicted (mean; SD) 93.0 (14.2) KCO (mean; SD) 2.95 (1.0) KCO % of predicted (mean; SD) 57.9 (16.3) Obstructed (n°; %) 7/81 (8.6) Restricted (n°; %) COMORBIDITIES Cardiovascular disease (n°; %) 8/81 (9.9) Diabetes Mellitus (n°; %) 12/81 (14.8) Obesity (n°; %) 3/81 (3.7) Previous history of neoplasm (n°; %) 6/81 (7.4)

Results 0.03 0.07 Survived Dead p-value FEV1 liters (mean; SD)   Survived Dead p-value FEV1 liters (mean; SD) 3.1 (0.72) 2.8 (0.85) 0.19 FEV1 % of predicted (means; SD) 101.2 (15.4) 92.4 (18.6) 0.03 FVC liters (mean; SD) 3.90 (0.85) 3.65 (1.00) 0.26 FVC % of predicted (mean; SD) 104.2 (16.0) 95.6 (15.9) RV % of predicted (mean; SD) 88.5 (20.2) 84.4 (29.6) 0.51 TLC liters (mean; SD) 5.64 (1.1) 5.71 (1.5) 0.83 TLC % of predicted (mean; SD) 95.3 (14.0) 89.4 (13.6) 0.10 DLCO % of predicted (mean; SD) 72.6 (19.9) 63.1 (12.9) 0.07 KCO (mean; SD) 3.22 (1.1) 2.52 (0.8) KCO % of predicted (mean; SD) 59.7 (17.5) 54.3 (15.2) 0.32

Results Post-transplant pulmonary infection (all) No Yes p-value FEV1 liters (mean; SD) 2.99 (0.75) 3.0 (0.76) 0.84 FEV1 % of predicted (means; SD) 98.7 (16.8) 96.3 (17.2) 0.53 FVC liters (mean; SD) 3.78 (0.94) 3.82 (0.85) 0.85 FVC % of predicted (mean; SD) 102.4 (16.3) 98.9 (16.5) 0.35 RV % of predicted (mean; SD) 91.5 (23.7) 85.0 (25.7) 0.30 TLC liters (mean; SD) 5.49 (1.2) 5.80 (1.3) 0.33 TLC % of predicted (mean; SD) 94.6 (16.2) 91.9 (12.9) 0.46 DLCO % of predicted (mean; SD) 72.2 (18.5) 67.7 (17.5) 0.43 KCO (mean; SD) 2.96 (1.4) 2.94 (0.8) 0.96 KCO % of predicted (mean; SD) 63.4 (20.9) 54.6 (12.2) 0.08 Post-transplant early pulmonary infection (within 100 days) No Yes p-value FEV1 liters (mean; SD) 3.0 (0.77) 2.8 (0.69) 0.39 FEV1 % of predicted (means; SD) 98.6 (15.9) 90.1 (21.4) 0.11 FVC liters (mean; SD) 3.83 (0.92) 3.66 (0.74) 0.55 FVC % of predicted (mean; SD) 101.6 (16.0) 93.7 (18.0) 0.13 RV % of predicted (mean; SD) 88.8 (23.3) 80.2 (34.1) 0.34 TLC liters (mean; SD) 5.62 (1.26) 6.0 (1.3) 0.41 TLC % of predicted (mean; SD) 92.7 (14.6) 94.8 (11.9) 0.69 DLCO % of predicted (mean; SD) 68.7 (18.0) 72.6 (17.4) 0.58 KCO (mean; SD) 2.89 (1.11) 3.20 (0.86) 0.46 KCO % of predicted (mean; SD) 57.9 (17.4) 57.9 (11.1) 0.99 Post-transplant late pulmonary infection (more than 100 days) No Yes p-value FEV1 liters (mean; SD) 3.0 (0.73) 2.9 (1.0) 0.86 FEV1 % of predicted (means; SD) 97.0 (17.6) 100.1 (10.0) 0.63 FVC liters (mean; SD) 3.81 (0.83) 3.73 (1.41) 0.80 FVC % of predicted (mean; SD) 100.4 (16.8) 101.1 (12.6) 0.90 RV % of predicted (mean; SD) 87.3 (24.8) 90.6 (27.7) 0.74 TLC liters (mean; SD) 5.71 (1.17) 5.36 (1.98) 0.66 TLC % of predicted (mean; SD) 93.3 (14.1) 0.64 DLCO % of predicted (mean; SD) 68.7 (18.0) 72.6 (17.4) 0.53 KCO (mean; SD) 2.96 (1.05) 2.89 (1.06) 0.89 KCO % of predicted (mean; SD) 56.7 (16.0) 66.8 (18.8) 0.20

Limitations We ignore whether results obtained by Cyranose and by Bionote are fully comparable. The number of patients studied allows hypothesize, but it cannot definitively prove, that OSAS patients segregate into two main groups with regard to basal BPs and CPAP related changes. A testing population would make our results more solid. A broader population would definitively prove the role of comorbidity in determining VOCs spectrum and its changes after CPAP. The classificatory role of comorbidity would be better defined by integrating the list of comorbid diseases with some index of severity of diseases.

Conclusions In an OSAS population breath fingerprint dramatically changes after the first night of CPAP, suggesting immediate metabolic effects of nocturnal ventilation. Comorbidity seems to play a primary role in conditioning such a change. These findings might help to explain phenotypic variability in OSAS as well as to improve the monitoring of these patients. Breath fingerprint might qualify as a mean of assessing in a very simple and inexpensive way the response and, later, the adherence to CPAP.

Thank you for your attention Lung function prior to stem cell transplant as a predictor of infectious and pulmonary complications and survival in adults with haematologic malignancies Thank you for your attention s.scarlata@unicampus.it 14