Letter to the Editor
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2020; 12(11): 1429-1438
Published online Nov 26, 2020. doi: 10.4252/wjsc.v12.i11.1429
Acquired aplastic anemia: Is bystander insult to autologous hematopoiesis driven by immune surveillance against malignant cells?
Xi-Chen Zhao, Xiao-Yun Sun, Bo Ju, Fan-Jun Meng, Hong-Guo Zhao
Xi-Chen Zhao, Xiao-Yun Sun, Bo Ju, Department of Hematology, The Central Hospital of Qingdao West Coast New Area, Qingdao 266555, Shandong Province, China
Fan-Jun Meng, Hong-Guo Zhao, Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
Author contributions: Zhao XC, Sun XY, and Ju B performed the research work, analyzed the data, and drafted the manuscript; Meng FJ and Zhao HG supervised the treatment and revised the manuscript; all authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong-Guo Zhao, MD, Chief Doctor, Professor, Department of Hematology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong Province, China. zhaohongguo6201@163.com
Received: February 14, 2020
Peer-review started: February 14, 2020
First decision: September 11, 2020
Revised: September 20, 2020
Accepted: September 25, 2020
Article in press: September 25, 2020
Published online: November 26, 2020
Processing time: 286 Days and 9.1 Hours
Abstract

We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations (GCPs). This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments, with each recurrence occurring 7-8 wk from a GCP. After his third recurrence, he was prescribed successive treatment with rifampicin, berberine, and monthly administered GCP for 4 mo, and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy, and eventually died of septic shock. Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis. From the treatment process and laboratory investigations, it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state. Incorporation of rifampicin, berberine, and monthly GCP into cyclosporine can enhance the immunosuppressive effect. In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure, the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.

Keywords: Acquired aplastic anemia; Bystander insult; Malignant clonal hematopoiesis; Immune surveillance; Antineoplastic; Gut inflammation

Core Tip: We previously reported a severe aplastic anemia patient who had gotten an unexpected hematological response to treatment with intermittent gut-cleansing preparations. After his third recurrence, he was prescribed successive treatment with rifampicin, berberine, and monthly administered gut-cleansing preparations for 4 mo, and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy. We hereby make an extrapolation that, in a subgroup of aplastic anemia patients, the suppressed normal hematopoiesis may result from the bystander insult that is generated in response to the antigenic products of damaged hematopoietic cells, and may offer a protective antineoplastic mechanism against malignant proliferation.