Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome:A case report and review of literature

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.

Diagnosis of Infectious Mononucleosis by Combined Detection of Atypical Lymphocytes and Transaminase

In order to explore the value of combined detection of atypical lymphocytes （ATL） and transaminase （alanine aminotransferase, ALT＇ asparate aminotransferase, AST） in the diagnosis of infectious mononucleosis （IM）, The data of blood routine and liver function were collected from 54 IM patients, 34 acute hepatitis （AH） patients, 44 upper respiratory infection （URI） patients in Union Hospital during March 2002 to March 2005. Same data were also collected from 40 healthy children as normal control. These data were analyzed retrospectively. Both proportion of atypical lymphocytes and enzyme activity of transaminase were elevated simultaneously （ALT〉40 IU/L, AST〉45 IU/L） in 57.4% （31/54） IM patients. There was significant difference （P〈0.01） between IM group and the other groups. Combined detection of atypical lymphocytes and transaminase can be regarded as a diagnostic marker of infectious mononucleosis.

Glutathione Reductase, Liver Transaminases and Atypical Lymphocytes Count as Early Predictive Biomarkers in Diagnosis of Thrombocytopenia in Dengue Viral Infection

Objective: The aim of the study is to identify whether Atypical Lymphocyte (AL), liver transaminases, and Glutathione Reductase (GR) can be used as potential biomarkers in the assessment of severity and thrombocytopenia in dengue. Methods: A cross-sectional analytical study was carried out on diagnosed dengue patients admitted to Nawaloka Hospital, Sri Lanka. Blood samples were taken from patients (n = 50) on the day of admission, 3rd and 5th day from admission for analysis of GR, aspartate transaminase, alanine transaminase, platelets, white blood cells, and Atypical Lymphocytes (AL). Results: GR level of all three measured stages had a higher area under the curve (>88%), high sensitivity and specificity compared to liver transaminases. A significant regression model represents on admission GR and AL levels as predictive variables to platelet levels in day 03 from admission (Day 3 Platelet level = 127155.3 - 383 * GR - 0.431 * AL). Conclusion: Liver transaminases, GR, and AL% can be considered as a profile of predictive biomarkers in early diagnosis of severity of dengue infection. The degree of thrombocytopenia can be predicted using on admission GR and AL% level in acute dengue viral infection.

Measurement of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome and its clinical significance

Objective To investigate the changes of subgroups of peripheral blood T lymphocytes in patients with severe acute respiratory syndrome (SARS) and its clinical significance.Methods Subgroups of blood T lymphocytes in 93 patients with SARS were detected by flow cytometer. The results detected in 64 normal subjects and 50 patients with AIDS served as controls.Results The numbers of CD3 +, CD4 +, and CD8 + lymphocytes all significantly decreased in acute phase of patients with SARS [(722±533)/μl, (438 ±353)/μl, (307±217)/μl)] compared with those in normal controls [ (1527±470)/μl, (787±257)/μl, (633±280)/μl, all P<0. 01) ], which was different from what we observed in patients with AIDS who had decreased CD4 + [ (296±298)/μl] but increased CD8 + [ (818 ±566)/μl counts. The counts of CD3+, CD4+, and CD8 + lymphocytes decreased more apparently in patients with severe SARS. All the five patients who died had CD4 + counts less than 200/μl. As the patients' condition improved, CD3 +, CD4 +, and CD8 + counts gradually returned to normal ranges.Conclusion The damage of cellular immunity is probably an important mechanism of pathogenesis of SARS.