Case Report
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 6, 2023; 11(28): 6908-6919
Published online Oct 6, 2023. doi: 10.12998/wjcc.v11.i28.6908
Leukemic transformation during anti-tuberculosis treatment in aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome: A case report and review of literature
Nuan-Nuan Xiu, Xiao-Dong Yang, Jia Xu, Bo Ju, Xiao-Yun Sun, Xi-Chen Zhao
Nuan-Nuan Xiu, Xiao-Dong Yang, Jia Xu, Bo Ju, Xiao-Yun Sun, Xi-Chen Zhao, Department of Hematology, The Central Hospital of Qingdao West Coast New Area, Qingdao 266555, Shandong Province, China
Author contributions: Zhao XC developed the idea; Xiu NN and Yang XD analyzed the data and drafted the manuscript; Xiu NN, Yang XD, Xu J, Ju B and Sun XY participated in patient treatment; Zhao XC revised the manuscript; All the authors have read and approved the final manuscript.
Informed consent statement: Informed written consent was obtained from the patient to publish this case report and any accompanying laboratory data.
Conflict-of-interest statement: The authors have no conflicts of interest to declare that are relevant to the content of this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xi-Chen Zhao, MD, Chief Physician, Department of Hematology, The Central Hospital of Qingdao West Coast New Area, No. 9 Huangpujiang Road, Qingdao 266555, Shandong Province, China. zhaoxichen2003@163.com
Received: June 29, 2023
Peer-review started: June 29, 2023
First decision: August 9, 2023
Revised: August 18, 2023
Accepted: September 6, 2023
Article in press: September 6, 2023
Published online: October 6, 2023
Processing time: 88 Days and 0.5 Hours
Abstract
BACKGROUND

Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution. In approximately 10%-15% of patients with severe aplastic anemia (SAA), the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy. In some of these patients, myeloid neoplasms appear during or shortly after immunosuppressive therapy. Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported.

CASE SUMMARY

A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria (PNH). With aggravation of systemic inflammatory symptoms, severe pancytopenia developed, and her hemoglobinuria disappeared. Laboratory findings in cytological, immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for “SAA.” Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches. Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment, and complete hematological remission was achieved within 4 mo of treatment. Frustratingly, the hematological response lasted for only 3 mo, and pancytopenia reemerged. At this time, cytological findings (increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0% of all nucleated hematopoietic cells), immunological findings (increased percentage of cluster of differentiation 34+ cells that accounted for 12.28% of all nucleated hematopoietic cells) and molecular biological findings (identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes) revealed that “SAA” had transformed into acute myeloid leukemia with mutated nucleophosmin-1. The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages, as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo. Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis, and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis. The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism.

CONCLUSION

Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis, and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.

Keywords: Aplastic anemia; Paroxysmal nocturnal hemoglobinuria; Acute myeloid leukemia; Tuberculosis; Leukemic transformation; Case report

Core Tip: A Chinese female had a 6-year history of nonsevere aplastic anemia and a 2-year history of paroxysmal nocturnal hemoglobinuria. With aggravation of systemic inflammatory symptoms, severe pancytopenia developed, and her hemoglobinuria disappeared. Laboratory findings met the diagnostic criteria for “severe aplastic anemia.” Anti-tuberculosis treatment resulted in leukemic transformation after a short duration of hematological remission. This case study revealed that aggravated inflammatory stressors can repress normal and leukemic hematopoiesis, and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis, suggesting an inflammatory stress-fueled antileukemic mechanism.