Influenza A (H1N1) in a Pediatric Patient With Newly Diagnosed Acute Promyelocytic Leukemia and Invasive Pulmonary Aspergillosis Stefano Vallero, MD,* Francesca Carraro, MD,* Franca Fagioli, MD,* AnnaMaria Postini, MD,* Elisa Rivetti, MD,* Stefania Bezzio, MD,w and Mareva Giacchino, MD* Summary: Influenza A (H1N1) pandemic reached its peak in Europe in autumn 2009. H1N1 infection can be a serious complication in patients with comorbidity or immunodepression. Here, we report of a boy with newly diagnosed acute promyelocytic leukemia with a very severe respiratory distress caused by influenza A (H1N1) infection in pulmonary aspergillosis, successfully treated with antifungal therapy, oseltamivir, and extracorporeal membrane oxygenation. Key Words: acute promyelocytic leukemia, immunodepression, influenza A (H1N1), aspergillosis (J Pediatr Hematol Oncol 2011;33:562–564) I n April 2009, a novel influenza A (H1N1) virus outbreak was reported in Mexico. Subsequently, several cases were reported worldwide 1 ; by June 11, 2009, the World Health Organization declared the phase 6 “pandemic” alert level. 2 Differently to seasonal influenza, mortality from influ- enza A (H1N1) is worse in infants, young adults, pregnant women, and pathologically obese patients. 3 Neuraminidase inhibitors, such as oseltamivir and zanamivir, have been proposed as adequate treatment for patients with severe infection or relevant risk factors such as obesity, pregnancy, and immunodepression. Oseltamivir has been widely used among the pediatric population, too. 4,5 Influenza A (H1N1) infection has been a matter of concern in the setting of the pediatric hemato-oncologic patient care owing to concomitant morbidity and mortality risk factors in children treated for cancer. Any severe viral infection can be dangerous in such patients, especially during the induction phase, when intensive chemotherapy, tumor lysis, and deteriorated patient’s general conditions may impair immunity and favor infection. 5,6 Invasive aspergillosis is one of the most threatening fungal infections in patients who are being treated for can- cer owing to immunodepression and prolonged neutropenia. 7 We describe the case of a patient with influenza A (H1N1) and Aspergillus fumigatus pulmonary infection, diagnosed during induction treatment for acute promyelo- cytic leukemia (APL). In this patient, multiple severe risk factors coexisted: acute leukemia, induction chemo- therapy, hemorrhage, poor general conditions, and con- tinued hospitalization. CASE REPORT A 10-year-old-boy was admitted to our onco-hematology unit for fever and hemorrhagic diathesis. The patient had previously been healthy, and was not obese, his body mass index being at 75th centile. Complete blood count showed white blood cell count (WBC) 30.15 10 9 /L, hemoglobin 7.2 g/L, and platelet 18 10 9 /L. Coagu- lation examinations were altered (prothrombin time 53%, interna- tional normalized ratio 1.47, activated partial thromboplastin time 38.5 s, D-dimer 33.91 mg/L). Peripheral blood smear showed 90% myeloid blasts, consistent with acute promyelocytic leukemia (APL), French-American-British classification M3. The diagnosis was confirmed on bone marrow (BM) aspiration (95% blasts). Rearrangement t(15;17)(PML-RARalpha) was found to be positive (breakpoint bcr1) at molecular analysis. The karyotype on BM was 46,XY,t(15;17)(q22;q21). The patient was then enrolled in the International Children Cancer APL Study 01 protocol, high-risk group. Chest x-ray was normal at diagnosis. Antibacterial and antifungal prophylaxis with beta-lactam and fluconazole was started. One week after the diagnosis, the patient presented high temperature (401C), mild dyspnea, and cough; the patient was neutropenic (WBC 0.2 10 9 /L, neutrophil 0.03 10 9 /L); a computed tomography scan showed whole inferior right lobe parenchymal consolidation, multiple hyperdensity areas on both lungs, with a slight bilateral pleural effusion. Urine Pneumococcus and Legionella antigen search was negative. Antigenemia for Aspergillus (Platelia) was found to be positive on 2 subsequent controls. Owing to the possible interaction between 13-all-trans-retinoic-acid (used in APL in induction phase) and azoles, liposomal amphotericin B at 3 mg/kg/d was chosen as antimycotic therapy. Fifteen days after the diagnosis, the patient worsened further, with severe dyspnea, tachypnea, tachycardia, and supraclavicular and sternal retraction. Blood oxygen saturation values were in the range of 75% to 85% in air and 90% with O 2 therapy at 8 L/min. Chest x-ray showed severe bilateral perihilar and inferior lobe congestion and condensation, which was more evident on the right side, with aerial bronchogram. Blood SeptiFast examination 8 was positive for A. fumigatus infection, thus antimycotic combination therapy (liposomal amphotericin B at 3 mg/kg/d plus caspofungin at 50 mg/m 2 /d) was started. 9 The chemotherapy was then interrupted and the patient was transferred to the intensive care unit (ICU). At ICU admission, blood count showed WBC 0.4 10 9 /L (neutrophils 0.1  10 9 /L). The patient’s progressive respiratory failure was unresponsive to noninvasive ventilation and his conditions gradually worsened. Two days after the ICU admission, and 9 days after the beginning Copyright r 2011 by Lippincott Williams & Wilkins Received for publication May 17, 2010; accepted April 8, 2011. From the *Onco-hematology Unit; and wInfectious Disease Unit, Pediatric Hospital “Regina Margherita,” Torino, Italy. Sources of Support: No sources of support have been used for the preparation of this paper. The authors declare no conflict of interest. Reprints: Stefano Vallero, MD, Oncoematologia Pediatrica, Ospedale Infantile Regina Magherita, Piazza Polonia Torino, Italy (e-mail: stefano.vallero@gmail.com; stefanogabriele.vallero@unito.it). CLINICAL AND LABORATORY OBSERVATIONS 562 | www.jpho-online.com J Pediatr Hematol Oncol  Volume 33, Number 7, October 2011