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Disseminated infection with novel human adenovirus (genotype 79) following allogeneic hematopoietic stem cell transplantation

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Dear Editor, Human mastadenoviruses (HAdVs) infections following allogeneic hematopoietic stem cell transplantation (alloSCT) in a highly immunocompromised state mostly occur through adenovirus reactivation. Symptoms caused by adenovirus reactivation are regarded… Click to show full abstract

Dear Editor, Human mastadenoviruses (HAdVs) infections following allogeneic hematopoietic stem cell transplantation (alloSCT) in a highly immunocompromised state mostly occur through adenovirus reactivation. Symptoms caused by adenovirus reactivation are regarded as serious complications following allo-SCT [1]. As recently reported, “HAdV-79,” a novel adenovirus classified as B2, is found in sewage in Japan [2]. In the present article, we report a case of lethal HAdV-79 infection in a patient following allogeneic bone marrow transplantation The patient was a 67-year-old female with treatmentrelated myelodysplastic syndrome. Complete remission was achieved following two courses of treatment with cytarabine, aclarubicin, and G-CSF. Allogenic bone marrow transplantation was conducted from HLAand blood type-matched, sexunmatched unrelated donors pretreated with fludarabine, melphalan, and total body irradiation. Graft-versus-host disease prophylaxis consisted of tacrolimus and mycophenolate mofetil. On day 14, engraftment was confirmed. After day 70, pancytopenia developed and gradually progressed, and on day 89, the patient was diagnosed with secondary engraftment failure. On day 94, respiratory failure rapidly progressed, and the renal dysfunction further deteriorated. The patient was diagnosed with severe pneumonia and bilateral renal pelvic hemorrhage, post-renal failure due to thrombus. Ureteral stents were bilaterally placed to improve the renal failure. However, on day 103 after transplantation, the patient died of the progressive respiratory failure. Pathological autopsy revealed that multiple organs showed cells positive on HAdV immunostaining for virus detection (Fig. 1). To genotype the HAdVs, nested PCR was performed with the tissues of the paraffin sections [3]. The resulting PCR products were cloned into a TA-vector for sequencing. For genotyping, the sequences were compared with the known sequences of HAdVs. High homologies with the adenovirus B2 group were found: 98%with HAdV-11, 97%with HAdV55, and 99% with HAdV-79. By examining the characteristic sequences of the penton base-coding regions for each adenovirus subtype, the subtypes of the B2 group were examined. The penton base-coding regions of HAdV were amplified by PCR for comparison with the sequences of HAdV-79, demonstrating a matching rate of 100%. Thus, the genotype of the present case was identified as HAdV-79. HAdV infection following hematopoietic stem cell transplantation is a clinically severe complication [4, 5]. HAdV-79 is a novel mutant strain of B2 with the same nucleotide sequences of the pentonand hexon-coding regions as those of type 34 and of the fiber region as that of type 11. In Japan, no surveillance has been conducted on pneumonia and hemorrhagic cystitis caused by HAdVs after allo-SCT. Therefore, the pathogenicity of HAdV-79 type cannot be easily demonstrated. However, like other B2-type HAdVs, the HAdV-79 type was also demonstrated to be pathogenic, causing severe symptoms. HAdV-79 pathogenicity still remains unclear. However, as observed in the present case, HAdV-79 may cause lethal disseminated HAdV infection. Serious tissue injury was confirmed by autopsy. More cases should be examined to reveal its pathogenicity and epidemiological features of HAdV-79 * Yuichi Ikeda [email protected]

Keywords: infection; hadv; stem cell; transplantation; hematopoietic stem; following allogeneic

Journal Title: Annals of Hematology
Year Published: 2020

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