The ability to successfully transplant solid organs and hematopoietic stem cells represents one of the landmark medical achievements of the twentieth century. Solid organ transplantation has emerged as the standard of care for select patients with severe vital organ dysfunction and hematopoietic stem cell transplantation has become an important treatment option for patients with a wide spectrum of nonmalignant and malignant hematologic disorders, genetic disorders, and solid tumors. Although advances in surgical techniques, immunosuppressive management, and prophylaxis and treatment of infectious diseases have made long-term survival an achievable goal, transplant recipients remain at high risk for developing a myriad of serious and often life-threatening complications. Paramount among these are pulmonary complications, which arise as a consequence of the immunosuppressed status of the recipient as well as from such factors as the initial surgical insult of organ transplantation, the chemotherapy and radiation conditioning regimens that precede hematopoietic stem cell transplantation, and alloimmune mechanisms mediating host-versus-graft and graft-versus-host responses. As the population of transplant recipients continues to grow and as their care progressively shifts from the university hospital to the community setting, knowledge of the pulmonary complications of transplantation is increasingly germane to the contemporary practice of pulmonary medicine.

Rationale: Primary graft dysfunction is a severe acute lung injury syndrome after lung transplantation. Long-term outcomes of subjects with primary graft dysfunction have not been studied. Objectives: We sought to test the relationship of primary graft dysfunction with both short-and long-term mortality using a large registry. Methods: We used data collected on 5,262 patients in the United Network for Organ Sharing/International Society of Heart and Lung Transplantation registry between 1994 and 2000. We assessed outcomes in all subjects; to assess potential bias from the effects of early mortality, we also evaluated subjects who survived at least 1 year, using Cox proportional hazards models with time-varying covariates. Main Results: The overall incidence of primary graft dysfunction was 10.2% (95% confidence intervals [CI], 9.2, 10.9). The incidence did not vary by year over the period of observation (p ϭ 0.22). All-cause mortality at 30 days was 42.1% for primary graft dysfunction versus 6.1% in patients without graft dysfunction (relative risk ϭ 6.95; 95% CI, 5.98, 8.08; p Ͻ 0.001); among subjects who died by 30 days, 43.6% had primary graft dysfunction. Among patients surviving at least 1 year, those who had primary graft dysfunction had significantly worse survival over ensuing years (hazard ratio, 1.35; 95% CI, 1.07, 1.70; p ϭ 0.011). Adjustment for clinical variables including bronchiolitis obliterans syndrome did not change this relationship. Conclusion: Primary graft dysfunction contributes to nearly half of the short-term mortality after lung transplantation. Survivors of primary graft dysfunction have increased risk of death extending beyond the first post-transplant year.Keywords: acute lung injury; lung transplantation; outcomes; primary graft dysfunction; reperfusion injury Primary graft dysfunction (PGD), also known as primary graft failure, is a form of lung allograft ischemia-reperfusion injury (1, 2). Occurring in the first hours to days after transplantation, the clinical course and pathophysiology of the most severe forms are most similar to the acute respiratory distress syndrome (1,3,4). With an incidence reported between 10 and 25%, and a high mortality (5), PGD represents the leading cause of early death after transplantation (1, 2, 5-8).However, the long-term outcomes of PGD have not been (Received in original form September 20, 2004; accepted in final form March 3, 2005) Supported by grants NHLBI K23 HL04243 and the Craig and Elaine Dobbin Pulmonary Research Fund.Correspondence and requests for reprints should be addressed to

Information regarding treatment of post-transplant lymphoproliferative disease (PTLD) beyond reduction in immunosuppression (RI) is limited. We retrospectively evaluated patients receiving rituximab and/or chemotherapy for PTLD for response, time to treatment failure (TTF) and overall survival (OS). Thirtyfive patients met inclusion criteria. Twenty-two underwent rituximab treatment, with overall response rate (ORR) 68%. Median TTF was not reached at 19 months and estimated OS was 31 months. In univariable analysis, Epstein-Barr virus (EBV) positivity predicted response and TTF. LDH elevation predicted shorter OS. No patient died of rituximab toxicity and all patients who progressed underwent further treatment with chemotherapy. Twenty-three patients received chemotherapy. ORR was 74%, median TTF was 10.5 months and estimated OS was 42 months. Prognostic factors for response included stage, LDH and allograft involvement by tumor. These factors and lack of complete response (CR) predicted poor survival. Twentysix percent of the patients receiving chemotherapy died of toxicity. Rituximab and chemotherapy are effective in patients with PTLD who fail or do not tolerate RI. While rituximab is well tolerated, toxicity of chemotherapy is marked. PTLD patients requiring therapy beyond RI should be considered for rituximab, especially with EBV-positive disease. Chemotherapy should be reserved for patients who fail rituximab, have EBV-negative tumors or need a rapid response.

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