Case Report
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 6, 2023; 11(19): 4713-4722
Published online Jul 6, 2023. doi: 10.12998/wjcc.v11.i19.4713
Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome: A case report and review of literature
Xiao-Yun Sun, Xiao-Dong Yang, Jia Xu, Nuan-Nuan Xiu, Bo Ju, Xi-Chen Zhao
Xiao-Yun Sun, Xiao-Dong Yang, Jia Xu, Nuan-Nuan Xiu, Bo Ju, Xi-Chen Zhao, Department of Hematology, The Central Hospital of Qingdao West Coast New Area, Qingdao 266555, Shandong Province, China
Author contributions: Zhao XC and Sun XY developed the idea; Sun XY, Yang XD and Xu J analyzed the data and drafted the manuscript; Sun XY, Yang XD, Xu J, Xiu NN and Ju B participated in the treatment; Zhao XC revised the manuscript; all authors have read and approved the final manuscript.
Supported by The Specialized Scientific Research Fund Projects of The Medical Group of Qingdao University, No. YLJT20201002.
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: April 10, 2023
Peer-review started: April 10, 2023
First decision: May 12, 2023
Revised: May 22, 2023
Accepted: May 31, 2023
Article in press: May 31, 2023
Published online: July 6, 2023
Processing time: 80 Days and 23.2 Hours
Abstract
BACKGROUND

Myelodysplastic syndrome (MDS) is caused by malignant proliferation and ineffective hematopoiesis. Oncogenic somatic mutations and increased apoptosis, necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells. An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage. Bone marrow cellularity and myeloblasts usually increase with disease progression. However, aplastic crisis occasionally occurs in advanced MDS.

CASE SUMMARY

A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1 (MDS-EB-1) based on an increase in the percentages of myeloblasts and cluster of differentiation (CD)34+ hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples. The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years. In the treatment process, the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia. During the aplastic crisis, the bone marrow was infiltrated with sparsely distributed atypical lymphocytes. Surprisingly, the leukemic cells disappeared. Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3, CD5, CD8, CD16, CD56 and CD57, suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer (NK)/NKT cells that suppressed both normal and leukemic hematopoiesis. Elevated serum levels of inflammatory cytokines, including interleukin (IL)-6, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), confirmed the deranged type I immune responses. This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia. Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche. Antituberculosis treatment led to reversion of the aplastic crisis, disappearance of the atypical lymphocytes, increased marrow cellularity and 2 mo of hematological remission, providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis, the regression of leukemic cells and the activation of CD56+ atypical lymphocytes. Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state. However, the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.

CONCLUSION

Disseminated tuberculosis can induce CD56+ lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis, resulting in the development of aplastic crisis and leukemic cell regression.

Keywords: Myelodysplastic syndrome; Aplastic crisis; Atypical lymphocyte; Leukemic cell regression; CD56+ lymphocyte expansion; Disseminated tuberculosis; Case report

Core Tip: In patients with myelodysplastic syndrome, bone marrow cellularity and myeloblasts usually increase with disease progression. An advanced myelodysplastic syndrome patient experienced an episode of aplastic crisis. During the aplastic crisis, leukemic cells regressed. The bone marrow was infiltrated with atypical lymphocytes that expressed high frequencies of cluster of differentiation (CD)3, CD5, CD8, CD16, CD56 and CD57. Antituberculosis treatment led to reversion of the aplastic crisis, disappearance of the atypical lymphocytes, increased marrow cellularity and 2 mo of hematological remission, suggesting that disseminated tuberculosis was responsible for the development of aplastic crisis, regression of leukemic cells and activation of CD56+ cells.