A 41-year-old man presented to our hospital with ecchymosis on the skin. She was found to be profoundly pancytopenia. The patient had no medical history.
The worst laboratory tests showed white blood cell count (WBC) 2.02×109/L, hemoglobin (Hb) concentration 58 g/L, neutrophil count 1.23×109/L, platelet (Plt) count 2×109/L and absolute reticulocyte count 17.2×109/L. Bone marrow biopsy revealed hypoplastic myelodysplasia, reduced granulocyte to erythrocyte ratio (G/E), and visible megakaryocytes with normal count and morphology. There was no significant increase in blasts by CD117 and CD34 staining, no significant increase in B- or T-cells by CD20 and CD3 staining, and no significant increase in plasma cells by CD138 staining. CK was negative and reticular fiber staining was Grade 0. Bone marrow smear revealed G/E = 2.81/1, reduced tri-lineage counts, and elevated lymphocyte ratio. Membrane antibody, platelet antibody, myelodysplasia–FISH panel, and PNH clones were negative, detected by flow cytometry. Chromosomal karyotype was normal. Prognostic leukemia genes were PPMID 20.61%, ASXL1 52.44%. Thrombopoietin receptor (TPO-R) expression rates on T-cell subsets were determined by flow cytometry as 19.82%, 62.45%, and 11.87% on CD4+, CD8 + and Treg cells, respectively. PET-CT revealed multiple hypermetabolic foci in the bone marrow, considered as a hematologic disease. The results of liver, renal function, and electrolyte tests were all within the normal range. Ferritin, folic acid, and vitamin B12 were not deficient. CMV-DNA and EBV-DNA were negative. Antinuclear antibody spectrum, tumor markers, and free thyroid function were normal.
After excluding other causes of pancytopenia, the patient met the criteria for severe aplastic anemia (SAA).
Considering the nephrotoxicity of cyclosporin A (CsA), She refused the immunosuppression therapy (IST) but received methylprednisolone (24 mg, three times daily) to regulate immunity. Moreover, she received hematopoietic therapy, including eltrombopag (50 mg daily), recombinant human erythropoietin (6000 IU, once every other day), and G-CSF (0.6 mL, daily), adjusted according to routine blood results. In addition, the patient was intermittently infused with red blood cells and platelets. Polyene phosphatidylcholine were provided to protect hepatocytes from toxic damage. After 2 weeks of treatment, her transaminase level increased significantly (AST, 27 U/L; ALT 79 U/L), possibly caused by eltrombopag-induced hepatotoxicity.
Eltrombopag was then replaced by avatrombopag, 40 mg daily, based on experience. Two weeks later, the transaminase level gradually returned to normal, and the patient tolerated the regimen well without any other side effects. The patient was then started on cyclosporin A (CsA; 50 mg, three times daily), with the concentration periodically monitored to adjust the dose. Peripheral hemogram characteristics improved slowly, and the frequency of component transfusion decreased over the treatment time. After 9 weeks of treatment, peripheral hemogram characteristics were significantly improved, red blood cell transfusions were no longer needed, and the platelet transfusion frequency was significantly reduced. Methylprednisolone dose was reduced to 12 mg per day, CsA was continued to correct the immune environment, and avatrombopag promoted bone marrow hematopoiesis. At 13 weeks of treatment, platelet transfusion was not necessary. The patient had an ongoing tri-lineage hematopoietic response at 1 month after the patient was completely free from blood transfusion. At that time, blood workup demonstrated Hb, 106 g/L; Plt, 50×109/L; ANC, 11.9×109/L; and Ret, 107.2×109/L. Bone marrow hyperplasia was significantly active, G/E was almost normal, dominant in mature cells and fewer megakaryocytes, and no special morphology was observed. TPO-R expression on T-cells was 48.76%, 25.50%, and 33.33% in CD4+, CD8+, and Treg cells, respectively, indicating that immune indicators were improved.
Follow-up and outcomes
Before report submission, the patient continued to receive avatrombopag and CsA treatment, and was in stable condition with a good quality of life.