The study will have two separate patient cohorts: Cohort 1 will include patients with newly diagnosed chronic graft versus host disease (GVHD), whereas cohort 2 will include patients with newly diagnosed chronic lung disease (CLD). For cohort 1, the primary objective will be to characterize PRM metrics at the onset of chronic GVHD and determine if a PRM signature is present that will predict 1-year CLD free survival. For cohort 2, the primary objective will focus on characterizing PRM at the onset of CLD and determine if PRM can predict the trajectory in lung function decline in affected patients.
Age ≥ 36 months. There is no upper age limit.
Receipt of an allogeneic HCT. There are no exclusions to study entry based upon primary diagnosis, hematopoietic cell source, conditioning regimen, donor type, degree of donor-recipient HLA match, or current organ function.
All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Cohort 1 (Chronic Graft Versus Host Disease): Diagnosis of chronic GVHD in at least 1 organ system within the prior 3 months. NIH Consensus Criteria for chronic GVHD are required to establish the diagnosis. (https://pubmed.ncbi.nlm.nih.gov/25529383/)
Relapse of a patient's primary malignancy post-HCT, or the development of any secondary "hematologic" malignancy post-HCT.
The presence of an active, uncontrolled infection.
Patients who would require intubation solely for the purposes of obtaining a CT scan for PRM imaging. (In contrast, if a clinical CT is being performed as routine medical care to evaluate a patient's lung function, the patient is eligible and PRM imaging may be performed from that CT.)
Pediatric and adult HCT populations
Cohort
Prospective
Not listed
1-year CLD free survival (Cohort 1)
The time to develop CLD or death over 12 months of follow-up in both pediatric and adult subjects will be determined. we will classify subjects into comparison groups of (1) high PRMfSAD (\>30%), (2) high PRMPD (\>40%) or (3) neither high PRMfSAD nor high PRMPD (PRMNorm group). The two primary analyses are to compare 1-year CLD-free survival between the high PRMfSAD and PRMNorm groups and separately between the high PRMPD and PRMNorm groups, using two-sided, two-sample logrank tests with an overall 5% type I error, adjusted for 2 comparisons using the Bonferroni method
FEV1 decline (Cohort 2)
Trajectory of FEV1 decline over a 12-month period in patients with newly diagnosed CLD. To evaluate PRM as a predictor of "lung function decline" in patients with an established diagnosis of CLD.
PRM profiles in children at the onset of chronic GVHD (Cohort 1)
Pediatric subjects will be enrolled into one of 2 strata (PFT+ vs PFTnull), PRM imaging with whole lung volumetric CT scans will be performed at baseline, using low dose CT techniques in children. Strata 1 (PFT+), the occurrence of CLD will be defined using NIH Consensus Criteria for BOS, or ISHLT criteria for RLD. Stratum 2 (PFTnull), radiographic findings of obstructive or restrictive lung disease on CT, plus clinical symptoms (dyspnea, or hypoxia) will be required to establish a diagnosis of CLD, in lieu of PFTs. PRM profile will be reported as percent functional small airway disease (PRMfSAD), emphysema (PRMEmph), parenchymal lung disease (PRMPD), and normal lung parenchyma (PRMNorm), in relation to the total lung volume.
Correlate PRM profiles at the onset of chronic GVHD with overall survival post-HCT (Cohort 1)
Subjects will be enrolled into one of 2 strata (PFT+ vs PFTnull), PRM imaging with whole lung volumetric CT scans will be performed at baseline.. For patients in strata 1 (PFT+), the occurrence of CLD will be defined using NIH Consensus Criteria for BOS, or ISHLT criteria for RLD. For patients in stratum 2 (PFTnull), radiographic findings of obstructive or restrictive lung disease (i.e. air trapping, bronchiectactic changes, interstitial fibrosis) on CT, plus clinical symptoms (dyspnea, or hypoxia) will be required to establish a diagnosis of CLD, in lieu of PFTs. Histograms of PRMfSAD, PRMPD, PRMEmph, and PRMNorm values will be displayed by pediatric stratum and overall, with means ± standard errors superimposed on the plots. PRM profile will be reported as percent functional small airway disease (PRMfSAD), emphysema (PRMEmph), parenchymal lung disease (PRMPD), and normal lung parenchyma (PRMNorm), in relation to the total lung volume.
To characterize a PRM profile for CLD in children post-HCT (Cohort 2)
We will have approximately 90% power to detect correlations \> 0.47 using 2-sided 1-sample correlation tests. This is a conservative estimate involving only the adult participants, with power increasing once pediatric participants are included in the analysis. In a secondary analysis we will use linear mixed effects models to study FEV1 predicted trajectories after CLD onset, as a function of PRM values. We will explore interactions between PRM values and time post-CLD when modeling FEV1 predicted values over time. PRM profile will be reported as percent functional small airway disease (PRMfSAD), emphysema (PRMEmph), parenchymal lung disease (PRMPD), and normal lung parenchyma (PRMNorm), in relation to the total lung volume.
To determine a PRM profile for restrictive lung disease (RLD) in adults with chronic GVHD post-HCT (Cohort 2)
We will have approximately 90% power to detect correlations \> 0.47 using 2-sided 1-sample correlation tests. This is a conservative estimate involving only the adult participants, with power increasing once pediatric participants are included in the analysis. In a secondary analysis we will use linear mixed effects models to study FEV1 predicted trajectories after CLD onset, as a function of PRM values. We will explore interactions between PRM values and time post-CLD when modeling FEV1 predicted values over time. PRM profile will be reported as percent functional small airway disease (PRMfSAD), emphysema (PRMEmph), parenchymal lung disease (PRMPD), and normal lung parenchyma (PRMNorm), in relation to the total lung volume.
Click on the lead sponsor to view all of their trials.
University of Michigan Rogel Cancer Center
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
