BACKGROUND: Pediatric oncology and hematopoietic stem cell transplantation (HSCT) patients are at high risk for influenza infection and its associated complications. Little is known about infection with novel 2009 influenza A (H1N1) in this population. PROCEDURE: Prospective laboratory surveillance identified all children with positive influenza test results from 4/27/09-12/5/09. 2009 H1N1 infection was confirmed by PCR subtyping; cases in which subtyping was not performed were considered probable. Medical records of all pediatric oncology and HSCT cases were reviewed. RESULTS: Thirty children with cancer or HSCT had laboratory-confirmed influenza A. Patients with ALL (18), CNS tumors (4), CML (1), Ewing sarcoma (1), Hodgkin lymphoma (1), LCH (1), severe aplastic anemia (1), and HSCT (3), had confirmed (5) and probable (25) H1N1 by rapid (22; 73%), DFA (4; 13%), or RVP (4; 13%) assays. Most frequent presenting signs and symptoms were fever (93%; median 38.6 degrees C), cough (97%), and rhinorrhea (83%). Ten patients required hospitalization for a median of 5 days, most commonly for fever and neutropenia (8). Imaging demonstrated lower respiratory tract involvement in three patients. There were no concomitant bacteremias; one patient had rhinovirus co-infection. Three patients required ICU care; 1 developed ARDS, multi-organ failure, and died after 5 days. Chemotherapy was delayed in five patients. Oseltamivir was administered to 28 patients; 1 patient developed an oseltamivir-resistant strain and was treated with zanamivir. CONCLUSIONS: 2009 influenza A H1N1 infection in children with cancer and HSCT is mild in most patients, but can lead to serious complications.