Flared inflammatory episode transforms advanced myelodysplastic syndrome into aplastic pancytopenia: A case report and literature review

Abstract

BACKGROUND Myelodysplastic syndrome (MDS) is a hematological neoplasm, and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS. Low-risk MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia (AA), whereas advanced MDS is characterized by a phenotype of immune exhaustion. MDS can be normo/hyperplastic or hypoplastic. Generally, bone marrow cellularity and myeloblasts increase with disease progression. Transformation from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been reported. CASE SUMMARY A middle-aged Chinese woman had a 4-year history of leukocytopenia. Six months prior to admission, the patient developed gradually worsening fatigue and performance status. The leukocytopenia further progressed. She was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears, an increased percentage of cluster of differentiation (CD)34+CD33+ progenitors in immunotyping analysis, a normal karyotype in cytogenetic analysis, and the identification of somatic mutations in CBL, KMT2D and NF1 in molecular analysis. Initially, neutropenia was the predominant hematological abnormality, with mild anemia and thrombocytosis, and the degree of fatigue was far more severe than the degree of anemia. In the following months, the patient experienced several febrile episodes. Intravenous antibiotic treatments were able to control the febrile episodes, but the elevated inflammatory indices persisted. The hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory episodes. With recurrent flares of the inflammatory condition, agranulocytosis and severe anemia developed, with mild thrombocytopenia. During the patient’s hospitalization, computed tomography (CT) scans revealed the presence of extensive inflammatory lesions involving the lungs, mediastinum, pleura, gastrointestinal tract, peritoneum and urinary tract, with imaging features suggestive of the reactivation of disseminated tuberculosis. Reevaluation of the bone marrow smears revealed that the cellularity became hypoplastic, and the leukemic cells regressed, suggesting that both normal and leukemic hematopoiesis had been heavily suppressed. Immunological analysis of the bone marrow samples revealed a decreased percentage of CD34+ cells and an immunological signature resembling that of severe AA (SAA), confirming the regression of the leukemic cells by autoimmune-mediated attacks. The patient demonstrated resistance to multiple drugs, including antituberculotics, recombinant human granulocyte colony-stimulating factor, broad-spectrum antibiotics, voriconazole, ganciclovir, immune suppressants, eltrombopag and intravenous immunoglobulin, which further worsened the hematological injury and patient’s performance status. The patient eventually died of overwhelming i...

When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms

“…The transformation between AHF and clinically overt MNs (MDS with excessive blasts or AML in which an increased percentage of myeloblasts is the most representative parameter in determining leukemic hematopoiesis) can reciprocally occur. The switch that shapes the disease phenotype is a change in the strength of extramedullary inflammatory conditions ( 33 – 36 ). Extramedullary infectious diseases have a conspicuous impact on phenotypic presentations.…”

“…During active inflammatory episodes, normal and leukemic hematopoieses are simultaneously suppressed with regression of leukemic blasts on cytological examination and Th1-predominant responses on immunological analysis. Aplastic cytopenia, the disappearance of leukemic blasts, Th1-predominant responses, and a small number of nucleated blood cells for identification of dysplasia result in cytological and immunological features that meet the criteria for the diagnosis of AA ( 33 – 36 ). Following successful control of the inflammatory episodes and a short duration of hematological remission, quickly expanded leukemic clones lead to the appearance of substantial leukemic blasts and symptomatic MNs ( 33 – 35 ).…”

“…Following successful control of the inflammatory episodes and a short duration of hematological remission, quickly expanded leukemic clones lead to the appearance of substantial leukemic blasts and symptomatic MNs ( 33 – 35 ). Patients with clinically overt MNs can develop an aplastic crisis during active inflammatory episodes in which systemic inflammatory stress is dramatically aggravated ( 35 , 36 ). Within this period, the BM becomes aplastic/hypoplastic, and leukemic blasts disappear with the infiltration of autoimmune lymphocytes.…”

“…This is because IST and treatment of underlying infections can rapidly change the host immune state without inducing novel genetic damage. An aplastic crisis with leukemic cell regression in definitively diagnosed MNs during inflammatory episodes provides a more persuasive argument for the influence of the host immune state on the disease phenotype ( 35 , 36 ).…”

“…This mechanism may play a more important role in MNs because blood cells are immune cells and their production is regulated largely in response to pathogen invasion ( 307 – 310 ). During active inflammatory episodes, TH1 immunity in response to invading pathogens powers antileukemic effects, which results in the regression of leukemic clones ( 33 – 36 ). After successful control of inflammatory diseases, suppressive effects on leukemic clones are mitigated and result in the penetration of morphologically identifiable leukemic hematopoiesis ( 35 ).…”