Abstract Introduction Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are uncommon World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH) phenotypes, together representing approximately 10% of group 1 PAH cases. PVOD is characterized by venular obstruction, profound hypoxemia, and a disproportionately low diffusing capacity for carbon monoxide (DLCO) often progressing rapidly despite therapy. Etiology remains incompletely defined. Cyclophosphamide, hematopoietic stem cell transplant, and primary malignancy physiology have each been implicated. This case highlights a PVOD phenotype arising before bone marrow transplant, with partial symptom responsiveness to lymphoma-directed therapy, raising the question that malignancy pathology rather than chemotherapy was the driver for the disease. Case Presentation A 72-year-old man with diffuse large B-cell lymphoma achieved complete remission after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Approximately one year later, he developed gradually progressive shortness of breath. Pulmonary function testing (PFTs) demonstrated preserved spirometry and lung volumes but severe isolated reduction in DLCO. Computed Tomography chest showed enlarged pulmonary vessels, mosaic ground glass opacities and mediastinal Lymphadenopathy. Echocardiography showed preserved left ventricular systolic function but moderately elevated right ventricular systolic pressures (RVSP) at 57 mmHg. As exertional dyspnea worsened, a six-minute walk test confirmed chronic desaturation requiring supplemental oxygen. He underwent right sided heart catheterization that demonstrated precapillary pulmonary hypertension with an elevated transpulmonary gradient (TPG) and normal pulmonary capillary wedge pressure (PCWP): Mean pulmonary artery pressure (mPAP) 31 mmHg, PCWP 6, TPG 25, Pulmonary vascular resistance (PVR) 5.29 wood units. He received salvage chemotherapy and was started on dual pulmonary arterial hypertension therapy with tadalafil and macitentan with symptomatic benefit. He later underwent autologous stem cell transplant and ultimately discontinued home oxygen. Follow-up imaging, two-dimensional Echocardiography and pulmonary function testing showed improvement of his elevated pulmonary pressures. Discussion This case raises two distinct etiologic possibilities: (1) cyclophosphamide-mediated endothelial injury and (2) active malignancy-driven vascular remodeling. The transient improvement during lymphoma cytoreduction is a key clue supporting cancer-related illness. While PVOD is traditionally associated with transplant, this case demonstrates development prior to transplant, reinforcing the need to consider malignancy as a causative agent. Early identification of PVOD as a cause of exertional dyspnea and hypoxemia in patients with hematological malignancy is essential, as prompt initiation of PAH-targeted therapy can enhance functional status and quality of life. This abstract is funded by: None
Allen et al. (Fri,) studied this question.