How I diagnose and treat organizing pneumonia in hematopoietic cell transplant recipients

Abstract

Organizing pneumonia (OP) is a known noninfectious pulmonary complication following allogeneic hematopoietic cell transplant (HCT) and represents a significant risk factor for nonrelapse mortality in HCT recipients. Unlike bronchiolitis obliterans syndrome, it is not universally acknowledged as a distinctive pulmonary manifestation of chronic graft-versus-host disease (cGVHD) and, therefore, its diagnostic criteria and management approach are lacking. Given its shared similar clinical features and radiological and histologic findings to OP in the non-HCT population, the diagnostic approach and treatment strategy for OP in HCT recipients is largely adapted from the non-HCT population. In this article, we aim to enhance the understanding of OP within the context of cGVHD following HCT and distinguish its clinical features and treatment strategy from non-HCT counterparts, thereby reinforcing its recognition as a pulmonary manifestation of graft-versus-host disease. We will propose the diagnostic criteria and outline our approach in diagnosis and treatment strategy, highlighting the potential challenges that may arise in each process. Finally, we will discuss knowledge gaps in this field and identify the area of need for future research.

Graphical abstract

Figure 1.

Representative coronal images from a noncontrast chest CT scan. (A) CT scan of the chest, demonstrating a right-sided upper lobe–predominant, peripheral ground-glass opacity at the diagnosis of organizing pneumonia. (B) CT images after 4 months of treatment with prednisone, demonstrating resolution of opacities.

Figure 2.

Example of HCT-OP on CT scan of the chest. Noncontrast axial CT image, demonstrating multifocal consolidative and ground-glass pulmonary opacities. The atoll sign (arrowhead) can occasionally be seen and is characterized by central ground-glass opacity surrounded by dense consolidation, representing perilobular involvement, known as the reversed halo sign. Involvement in this case is predominantly peripheral, but HCT-OP can also be peribronchovascular, or occasionally nodular.

Figure 3.

Representative serial axial images of a noncontrast CT scan of the chest for case 2. (A) Axial CT image, showing peribronchovascular consolidations and ground-glass opacities in the right upper lobe. (B) Image showing a complete resolution of radiographic abnormalities after escalating prednisone to 1 mg/kg per day and reinitiation of mycophenolate mofetil. (C) Image showing reappearance of ground-glass opacities with peribronchovascular consolidations in the right upper lobe when the prednisone was tapered to 10 mg/d and positive cytomegalovirus PCR in BAL. Notably, lung findings appear similar to panel A, when his HCT-OP was initially diagnosed.

Figure 4.

Graph of forced expiratory volume in 1 second (FEV₁), forced vital capacity (FVC), and DLCO (percentage) in relation to immunosuppressive therapy (prednisone and ibrutinib [mg]) and HCT-OP relapse for case 3.

Figure 5.

Approach to treatment for HCT-OP. BMT, bone marrow transplant; ICID, immunocompromised infectious disease.

Figure 6.

Representative of PFT trend in relation to clinical course and axial images of noncontrast CT scan of the chest for case 4. (A) PFT trend (FVC, forced expiratory volume in 1 second [FEV₁], and DLCO) during clinical course. (B) Axial CT image, showing basilar predominant ground-glass opacities with peripheral and peribronchovascular distribution, representing HCT-OP. (C) CT scan, showing worsened subpleural ground-glass opacities while immunosuppression was rapidly tapered during reactivation of CMV viremia. Escalation of prednisone was not pursued given clinical stability and ICU admission for CMV viremia and Klebsiella bacteremia. (D) CT image, showing similar subpleural ground-glass opacities, while FEV₁ continued to decline and patient experienced worsening dyspnea on exertion.

Figure 7.

Representative of parametric response mapping analysis for case 4. Dual-phase chest CT scanned at both end inspiration (total lung capacity) and end expiration (residual volume) and analyzed using parametric response mapping, showing 32% functional low-density area representing air trapping (yellow). This was taken at time point 3 on PFT trend (Figure 6A).