Experience of Therapy for Pneumonia In Hematopoietic Stem Cell Transplant Recipients Infected by Influenza 2009 H1N1.
Authors: Luo Yi , Fu Huarui , Tan Yamin , Zheng Yanlong , Shi Jimin , He Jingsong , Wu Wenjun , Xie Wanzhou , Xiao Haowen , Cai Zhen , Ye Xiujin , Lin Maofang , Huang He 
Published: October 2019

Abstract
Abstract 4553
In March 2009, a novel influenza H1N1 2009 virus was firstly detected in Mexico and then spread throughout the world rapidly. Till now, data about severe cases infected by 2009 H1N1 following allogeneic hematopoietic stem cell transplantation (allo-HSCT) are sparse, with only 11 anecdotal cases reported. We first describe three cases of influenza A/H1N1 2009 infection following allo-HSCT in China, including the first report in a haploidentical allo-HSCT recipient. The main clinical presentation in all cases are classic pneumonia-like symptoms and H1N1 virus was isolated from throat swabs in all patients. All patients received oral oseltamivir 75 mg twice a day, broad-spectrum antibiotic and anti-fungi drugs were given at the same time for co-infection. Two patients achieved complete resolution with this treatment regimen, the haploidentical HSCT recipient finally died of ARDS. Our cases suggest combination of oseltamivir, more effective of prophylaxis of co-infections and better supportive care is an effective treatment for influenza A/H1N1 2009 pneumonia in immunodeficient patients. The first case, a 16-year-old male, was diagnosed with acute lymphocytic leukemia (ALL-L2) in April 2008. He received HLA-identical sibling peripheral blood stem cells transplantation (allo-PBSCT) in October 23, 2008. Acute and chronic GVHD were not observed. He was admitted to our hospital for pharyngodynia, rhinobyon, exacerbated cough accompanied by pricked dyspnea on November 2009. Broad-spectrum antibiotic were administered for 3 days and no significant clinical improvement was observed. High-solution chest CT showed bilateral multiple flaky infiltrating. Influenza 2009 H1N1 virus was subtyped in his throat swab by real-time quantitative PCR (RT-PCR) analysis using validated CDC published primer/probe sets septic for variant 2009 H1N1 virus. The second case, a 25-year-old female, was diagnosed with acute lymphocytic leukemia (ALL-L2, B-cell, Ph-) in August 2008. She received HLA-identical unrelated donor (10/10 alleles matching) allo-PBSCT in April, 2009. She developed dermatosclerosis-like extensive cGVHD (skin) but the symptom was not improved after being treated with prednisone, thalidomide and tacrolimus. She was admitted to our hospital for palm infection in December, 2009. Chest CT showed lung infection and round lesion near the pleura. She was diagnosed with H1N1 influenza by RT-PCR analysis in throat swabs. The third case, a 42-year-old male, was diagnosed with acute lymphocytic leukemia (ALL-L2) with positive Bcr/Abl P190 fusion gene in October 2008. He received HLA-haploidentical sibling (his daughter) allo-PBSCT in April 2009. The patient developed grade II aGVHD (skin) on day 14 after transplantation, He achieved excellent response by being treated with prednisone and FK506. He was admitted to our hospital for skin rush and hyperglycemia in December, 2009. His oxygen saturation was 93.3% on room air. Chese CT showed interstitial ground glass-like changes in both lungs, and consolidation in both lobus inferior pulmonis. The patient developed progressive tachypnea after 4 days and was diagnosed with H1N1 influenza by RT-PCR analysis in throat swabs. All patients were nursed in H1N1-ICU ward for further treatment as soon as being diagnosed. Oseltamivir (75 mg twice a day) was given with broad-spectrum antibiotic and anti-fungi drugs. The first and second patients’ symptoms were improved after 2 weeks, and recurrent throat swab examination was negative. The third patient was continued mechanical ventilation, Chest CT show infection was progressive and infiltrating in the whole lung. In January 7, 2010, the patient's oxygen saturation decreased to 50% and malignant ventricular arrhythmias were observed. Although with cardio pulmonary resuscitation for more than 1 hour, the patient died of ARDS. Our experience highlights on the severity of 2009 H1N1 infection in post-transplantation recipients. Haploidentical transplantation is an independent adverse prognostic factor. Oseltamivir is an effective therapy for pneumonia infected by 2009 H1N1, broad-spectrum antibiotic and anti-fungi drugs should be given at the same time.

Disclosures:
No relevant conflicts of interest to declare.