Care of the Critically Ill Pediatric Hematopoietic Cell Transplant Patient

Although potentially curative therapy, hematopoietic cell transplantation (HCT) is fraught with many unique and life-threatening complications. Pulmonary complications, both infectious and noninfectious, are common and a significant source of nonrelapse mortality. Noninfectious pulmonary complications include a variety of etiologies difficult to diagnose and treat. Cardiac complications are less common and include primarily arrhythmias and cardiomyopathy. Sinusoidal obstruction syndrome/hepatic veno-occlusive disease is a potentially life-threatening complication occurring in up to 30% of pediatric HCT patients. Transplant associated thrombotic microangiopathy is characterized by de novo Coombs negative anemia, thrombocytopenia, elevated lactate dehydrogenase levels, proteinuria, hypertension, and schistocytes. It is associated with high rates of morbidity and mortality. Infections are common post-HCT and the stage of immune reconstitution affects which pathogens are most likely. Immunosuppression may obscure the typical signs/symptoms of infection. Engraftment syndrome is characterized by fever, vascular leak, dyspnea, organ dysfunction, rash, and diarrhea typically occurring within 4 days of granulocyte recovery. Acute graft versus host disease (GVHD) primarily affects the skin, liver, and intestinal tract; management is based on severity grade. Neurological complications are also common in HCT patients and may portend poor outcomes. Posterior reversible encephalopathy syndrome (PRES) occurs frequently in the first 100 days post-transplant, characterized by headache, seizures, mental status changes, visual changes, and hypertension. Although medications, metabolic aberrations and infections may all cause neurological symptoms post-HCT, it is important to consider CNS recurrence of malignancy as a source of the pathology. Post-transplant lymphoproliferative disease occurs and treatments continue to evolve. Chimeric antigen receptor (CAR) autologous T-cell immunotherapy is used to treat B-cell precursor acute lymphoblastic leukemia that is refractory or in relapse. It is associated with high remission rates, but also unique toxicities including cytokine release syndrome and CAR T-cell related encephalopathy syndrome (CRES)/immune effector cell associated neurotoxicity syndrome (ICANS).