Figures
- FIGURE 1
Study flow diagram for treatment. Patients identified by 01-XX. BM: bone marrow.
- FIGURE 2
Individual changes in a) forced vital capacity (FVC) and b) diffusing capacity of the lung for carbon monoxide (DLCO) during follow-up.
Tables
- TABLE 1
Baseline characteristics of patients
Low dose (10×106 MSCs) Intermediate dose (50×106 MSCs) High dose (100×106 MSCs) Total Subjects 3 3 7 13 Age years 60.5 (54.4–68.0) 65.6 (64.3–78.0) 70.2 (66.1–78.0) 68.0 (64.3–77.2) Male/female 3/0 3/0 6/1 12/1 Time since IPF symptoms years 4.1±1.7 3.5±3.7 3.0±1.6 3.3±2.1 Time since IPF diagnosis years 1.9±2.1 3.5±4.0 1.6±1.7 2.1±2.4 Current or former smoker 3 (100) 2 (66.67) 5 (71.43) 10 (76.9) Smoking pack-years 19.7±4.5 20.0±0 22.5±22.1 21.0±13.8 BMI kg·m−2 27.7±1.9 29.4±1.0 26.3±2.7 27.4±2.5 Baseline SpO2 96.0±2.6 94.7±0.6 95.3±1.6 95.3±1.7 MRC dyspnoea scale 0/1/2/3 1/1/0/1 1/2/0/0 0/6/1/0 2/9/1/1 Cough intensity 0/1/2/3 0/0/2/1 0/1/2/0 1/3/1/2 1/4/5/3 Cough frequency 5 (5–7) 3 (2–4) 3 (2–4) 3 (2–5) SGRQ symptoms 39.4 (23.8–50.7) 21.2 (0–39.0) 30.5 (23.8–36.9) 30.5 (23.8–39.0) SGRQ activity 67.2 (0–73.0) 67.1 (35.5–73.8) 48.3 (41.5–67.1) 48.5 (41.5–67.2) SGRQ impact 49.7 (0–50.1) 24.1 (11.6–36.0) 15.3 (10.3–30.6) 16.0 (11.6–36.0) SGRQ total 53.3 (4.0–57.1) 37.8 (20.5–49.0) 24.2 (23.2–44.1) 28.9 (23.2–49.0) Baseline PaO2 mmHg 76.7±14.2 72.7±4.7 68.0±4.1 71.3±7.9 FVC % pred 83.7±36.5 69.4±15.6 74.9±15.8 75.6±20.3 FEV1 % pred 82.3±33.3 75.2±12.0 77.1±16.7 77.9±18.9 FEV1/FVC % 78.7±2.1 84.0±7.5 80.1±7.3 80.7±6.4 TLC % pred 66.0±25.2 58.5±9.0 60.9±9.8 61.5±13.2 DLCO adj % pred 45.7±18.5 57.0±18.7 43.1±5.7 46.9±12.9 6MWD m 476.0±114.5 491.0±56.7 491.9±63.6 488±69.2 6MWT SpO2 nadir 87.0±8.9 88.0±1.7 77.9±6.8 82.3±7.9 HRCT findings Traction bronchiectasis 3 3 6 12 Reticular pattern 3 3 7 13 Honeycombing 1 2 7 10 Pulmonary biopsy 2 (66.67) 2 (100) 1 (14.29) 5 (38.5) Data are presented as n, median (interquartile range), mean±sd or n (%). MSCs: mesenchymal stromal cells; IPF: idiopathic pulmonary fibrosis; BMI: body mass index; SpO2: peripheral oxygen saturation; MRC: Medical Research Council; SGRQ: St George's Respiratory Questionnaire; PaO2: arterial oxygen tension; FVC: forced vital capacity; FEV1: forced expiratory volume in 1 s; TLC: total lung capacity; DLCO: diffusing capacity of the lung for carbon monoxide; 6MWD: 6-min walk distance; 6MWT: 6-min walk test; HRCT: high-resolution computed tomography.
- TABLE 2
Adverse events and outcomes
MedDRA code Patients Severity (mild/moderate/severe/life-threatening) Seriousness (nonserious/serious) First 3 months after infusion Outcome at 12 months Bronchitis 10006451 8 (61.5) 8/0/0/0 8/0 5 Resolved IPF clinical progression or worsening without hospitalisation 10067761 5 (38.5) 0/3/2/0 5/0 1 4 IPF progression
1 lung transplantIPF worsening with hospitalisation (2 patients) 10067761
100541123 (23.1)# 0/2/1/0 0/3 1 1 death Fever and/or dyspnoea after infusion 10013968
100376603 (23.1) 1/2/0/0 3/0 3 Resolved Upper respiratory tract infection/sinusitis 10046309 2 (15.4) 2/0/0/0 2/0 2 Resolved Flu-like syndrome 10022004 2 (15.4) 2/0/0/0 2/0 6 Resolved Acute gastroenteritis 10066762 1 (7.7) 1/0/0/0 1/0 1 Resolved Skin lesion 10040882 1 (7.7) 1/0/0/0 1/0 1 Resolved Legionella pneumonia with hospitalisation 10035718 1 (7.7) 0/0/0/1 0/1 0 1 death Abdominal pain, weight decreased, and general deterioration 10000081
10000159
100494381 (7.7) 0/1/0/0 1/0 1 1 death Prostate adenocarcinoma 10060862 1 (7.7) 0/1/0/0 0/1 0 On treatment Small cell lung cancer 10041067 1 (7.7) 1/0/0/0 0/1 0 On treatment Radiotherapy side-effects with hospitalisation (prostate cancer treatment) 10037759 1 (7.7) 0/1/0/0 1/0 0 Resolved Data are presented as n (%) or n. MedDRA: Medical Dictionary for Regulatory Activities; IPF: idiopathic pulmonary fibrosis. #: one patient was hospitalised twice during a 2-month period.
- TABLE 3
Changes in pulmonary function, 6-min walk test and quality of life
Time after infusion 1 month 2 months 3 months 6 months 9 months 12 months Subjects 13 11 13 10 7 6 ΔFVC mL −93±240 −184±272# −212±275# −200±240# −214±292 −212±189# ΔFVC % change −3.7±10.8 −6.8±12.7 −8.1±11.7 −7.7±10.5 −7.0±10.5 −7.6±6.4 ΔTLC mL 27±267 −79±187 −151±315 −169±370 −260±338 −345±374 ΔTLC % change 0.5±4.1 −1.3±2.9 −2.3±4.9 −2.7±5.9 −4.3±5.0 −5.5±5.5 ΔDLCO mL·mmHg−1·min−1 −0.2±1.3 −0.2±1.7 −1.1±1.7# −0.9±1.9 −1.2±2.3 n=6 −1.5±2.6 ΔDLCO % −1.7±11.1 −2.6±11.6 −9.5±14.2 −8.3±14.3 −12.1±16.8 n=6 −11.5±19.5 Δ6MWD m 5.3±32.4 9.0±34.6 1.8±71.4 −9.8±37.3 −40.0±83.1 −16.7±41.3 Patients with FVC decline <10% 11 7 7 6 4 4 Patients with DLCO decline <15% 12 10 8 7 2 4 ΔSGRQ symptoms 6.0±14.3 4.9±16.6 5.6±19.9 3.1±16.4 10.8±30.8 3.6±27.6 ΔSGRQ activity 3.7±16.7 −1.4±20.2 −0.8±23.2 −3.8±27.1 7.0±27.9 3.8±28.6 ΔSGRQ impact −0.5±11.3 −0.7±10.8 0±16.0 1.6±13.0 6.0±20.8 −2.9±15.3 ΔSGRQ total 0.7±11.2 −0.8±12.6 −0.5±16.2 −0.5±15.7 5.2±19.8 −2.0±17.6 Data are presented as n or mean±sd. FVC: forced vital capacity; TLC: total lung capacity; DLCO: diffusing capacity of the lung for carbon monoxide; 6MWD: 6-min walk distance; SGRQ: St George's Respiratory Questionnaire. #: significant change compared to baseline values, p<0.05.
- TABLE 4
Individual baseline and functional outcomes# at the end of follow-up
Patient identifier Dose n cells Baseline FVC % Baseline DLCO % Functional outcome at 3 months Last visit Overall outcome at last visit/ or follow-up contact Observations: death/lung transplant¶ 01_01 10×106 53 35 Progression 6 months Progression 01_03 10×106 74 35 Stable 3 months Other Lung transplant at 6 months 01_05 10×106 124 67 Stable 12 months Stable 01_06 50×106 57 42 Stable 9 months Progression 01_07 50×106 87 78 Progression 12 months Stable 02_01 50×106 64 51 Progression 12 months Progression 01_09 100×106 73 42 Progression 3 months Other Death at 5 months 01_10 100×106 61 35 Stable 9 months Progression 01_11 100×106 96 53 Stable 12 months Stable 01_13 100×106 90 47 Progression 12 months Progression 01_14 100×106 52 39 Stable 6 months Other Death at 8 months 01_15 100×106 69 43 Progression 3 months Other Death at 9 months 01_17 100×106 83 43 Progression 12 months Progression FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide. #: progression defined by fall in FVC ≥10% and/or fall in DLCO ≥15%, otherwise considered stable; ¶: causes of death: 01_09 Legionella pneumonia, 01_14 IPF progression, 01_15 not determined.
