The INTERCEPT™ Blood System (amotosalen + UVA illumination) for platelets is FDA-approved in the USA for the ex vivo preparation of pathogen-reduced, apheresis platelet components (PCs) to reduce transfusion-transmitted infection, including sepsis, and to potentially reduce the risk of transfusion-associated graft vs. host disease. Platelet transfusion is a potential risk factor for acute respiratory distress syndrome (ARDS), but the incidence of ARDS following platelet transfusion is not well-defined. A phase 3 study (SPRINT) of patients treated with INTERCEPT PCs vs. conventional PCs reported a frequency of ARDS of 1.6% vs. 0%, respectively (Snyder et al., Transfusion 2005;45:1864-1875). This unexpectedly low incidence of ARDS, owing to the lack of precise definitions, prompted the conduct of a blinded reanalysis using the American European Consensus Criteria for ARDS. Reanalysis demonstrated a frequency of ARDS of 6.0% and 4.9% for recipients of pathogen-reduced PCs and conventional PCs, respectively, with no significant treatment difference between groups (Corash et al., Blood 2011;117:1014-1020). Large scale active hemovigilance programs in Europe conducted by regulatory authorities from 2009-2014 reported no differences in the incidence of ARDS following platelet transfusion (0.33 vs. 0.32 cases per 10,000 platelets transfused). To evaluate the incidence of severe pulmonary adverse events requiring assisted ventilation in hematology-oncology (heme/onc) patients following the transfusion of apheresis derived INTERCEPT PCs compared to transfusion of conventional apheresis PCs. A prospective, non-randomized sequential cohort, open label, multi-center, non-inferiority, phase 4 surveillance study following transfusion of INTERCEPT PCs will be conducted. The patient population will be heme/onc hematopoietic stem cell transplant (HSCT) patients expected to require >1 PC transfusions. The proportion of patients requiring treatment-emergent assisted mechanical ventilation (TEAMV) during the observation period as defined by intubation or tight-fitting mask. TEAMV provides an objective measure of severe, clinically significant pulmonary injury. Patients will be assessed for TEAMV within 7 days after each study PC transfusion. 3000 patients allow for >90% power (one-sided alpha 0.025) for a non-inferiority margin of 0.023, assuming an event rate of 3.7% for the Control group. Events will be adjudicated by a blinded Pulmonary Expert Adjudication Panel. The PIPER study will address a significant deficit in the understanding of serious pulmonary events in heme/onc HSCT patients who require platelet support. It will be the first large controlled trial designed and powered to detect serious pulmonary adverse events in this patient population.