Purpose and Significance

Purpose

Hematopoietic stem cell transplant (HSCT) is a common and effective approach to treat malignancies and other diseases through the use of high dose chemotherapy and radiation with a significant risk of short- and long-term toxicity. Pulmonary morbidity affects as many as 25% of children receiving transplants. Early pulmonary injury includes diffuse alveolar hemorrhage (DAH), thrombotic microangiopathy (TMA), interstitial pneumonia syndrome (IPS), and infection while later, bronchiolitis obliterans (BO) is a troublesome manifestation of chronic graft-versus-host disease (GVHD). Better diagnosis and treatment of pulmonary complications are urgently needed as survival after HSCT improves, and HSCT is increasingly used for non-malignant disorders such as sickle cell disease. Currently, there are large and important gaps in our knowledge regarding incidence, etiology and optimal treatment of pulmonary complications. Moreover, in young children unable to perform spirometry pulmonary, complications are often diagnosed late and strategies for monitoring therapeutic response are limited.

In this study through the assembly of a large prospective uniformly screened cohort of children receiving HSCT, together with collection of biological samples, we will identify risk factors and mechanisms of lung injury, test novel diagnostic strategies and treatments to reduce morbidity and mortality from lung injury after transplant.

Significance

Hematopoietic stem cell transplantation (HSCT)-associated lung injury is an understudied complication of HSCT that significantly affects transplant related morbidity and mortality. Our understanding of the risk factors, natural history and pathogenesis of pulmonary complications after HSCT remains very limited, restricting progress of novel diagnostic and therapeutic approaches.

The data and biologic samples this study will generate will be critical to understand mechanisms and risk factors of HSCT induced lung injury allowing for identification of optimal screening, diagnostic and therapeutic modalities.