Multiple organ dysfunction syndrome in hematopoietic stem cell transplantation.

Abstract

To review the data demonstrating that central nervous system, pulmonary, and hepatic dysfunctions during hematopoietic stem cell transplantation have similar laboratory correlates and clinical outcomes, suggesting that they are individual organ manifestations of a systemic disorder at presentation, a disorder similar to the multiple organ dysfunction syndrome seen in other populations of critically ill patients. Reports of clinical research studies on the natural history and laboratory correlates of central nervous system, pulmonary, and hepatic dysfunction (generally manifesting as the syndrome of hepatic veno-occlusive disease) during hematopoietic stem cell transplantation. During hematopoietic stem cell transplantation, pulmonary dysfunction (manifesting as hypoxia), central nervous system dysfunction (detected by alteration of the Mini-Mental Status Exam), and hepatic dysfunction (presenting as the syndrome of hepatic veno-occlusive disease) are all associated with significant decreases in the levels of antithrombin III and protein C and an increase in the platelet transfusion requirement. Each of these three organ dysfunctions is associated with a high likelihood of being followed by the other two and, eventually, death. Patients with these organ dysfunctions have higher levels of interleukin-6, interleukin-10, and tumor necrosis factor-alpha than patients who never develop these complications. Mortality rates for patients with these organ dysfunctions vary from 15% in patients with only one organ dysfunction to 100% in patients who have progressed to all three. Patients who develop none of these organ dysfunctions have a mortality rate that approaches zero. Central nervous system, pulmonary, and hepatic dysfunctions are intimately involved in the mortal complications of hematopoietic stem cell transplantation. Because these organ dysfunctions have similar correlates and similar outcomes, the hypothesis that they are individual parts of a systemic disorder is proposed. The additional observation that these organ dysfunctions are associated with abnormally high levels of inflammation-related cytokines raises the possibility that their pathogenesis is similar to that of multiple organ dysfunction syndrome in other populations of critically ill patients.