Complications Arising from Preparatory Conditioning Regimens for Stem Cell Transplantation

Abstract

Hematopoietic stem cell transplantation (HSCT) has the potential to provide long-term survival and potential cure in patients with hematological malignancies and nonmalignant hematologic and autoimmune disorders. Conditioning regimens are designed to make room for the stem cell allograft by ablation of hosts’ immune system with the objective of sustained foreign immune cell engraftment. However, a number of short-term and long-term complications are associated with regimens used for preparatory conditioning in patients prior to allogenic stem cell infusion. Myeloablative conditioning regimens may cause significant toxicities, which include pancytopenia and injury to the orointestinal tract, brain, heart, liver, kidneys, and lungs. In order to mitigate such adverse events, reduced-intensity regimens have been developed. Emesis, anorexia, mucositis, and diarrhea are common orointestinal tract adverse events; sinusoidal obstruction syndrome is the main hepatotoxicity, and kidney injury may be either acute, or chronic. Treatment-induced defects in innate and adaptive immune function make patients susceptible to a variety of infections. Neurologic complications such as encephalopathy, seizures, cerebrovascular events, cognitive changes, and peripheral neuropathy are also not uncommon. Whereas early cardiac complications include congestive heart failure, arrhythmias, pericardial effusions, and endocarditis; whereas late cardiac complication also includes valvular heart disease. Lungs are a frequent site for such complications and include, acute pneumonitis, noncardiogenic pulmonary edema, diffuse alveolar hemorrhage, idiopathic pneumonia, as well as late obstructive and restrictive lung disease. Increased risk for bleeding may occur due to severe thrombocytopenia; additionally, hemolytic complications secondary to thrombotic microangiopathy may also be seen. Conditioning regimens may adversely affect the endocrine function such as, growth and skeletal development, metabolic functions, gonadal and sexual function, and fertility. Finally, high-dose chemotherapy and radiation therapy used in preparatory regimen may contribute towards an increased risk for cancers, mostly noted late after transplantation. In this chapter, a detailed review of complications associated with conditioning regimens given in preparation for stem cell allograft transplantation is presented.