The Effectiveness of Eltrombopag at the Different Stages of Aplastic Anemia and Probability of Clonal Expansion

Background. New insight into pathogenesis of aplastic anemia (AA) in conjunction with effectiveness of Eltrombopag allowes to recommend it for initial treatment of de novo AA. However, eltrombopag was an attractive option for patients at different stages of the therapy.

Aim. In our study we present various application points of eltrombopag as a therapeutic option in patients (pts) at different stages of the disease.

Materials and patients. We are presenting our single-center experience, that include 11 pts with acquired aplastic anemia (SAA/NSAA = 10/1) on different stages of the disease. All pts were divided into four groups. In the 1^st group we included refractory pts after two (n=3) or three (n=2) lines of antithymocyte globulin (ATG) therapy. The 2^nd group included two pts who received the second ATG course in combination with eltrombopag, after faild first ATG. In the 3^rd group included 2 pts with refractoriness after 1 course of ATG, who couldn't receive the second ATG/CsA because of severe infections. The 4^th group included two pts with one lineage thrombocytopenia but transfusion independent. The median time from the start of immunosuppressive therapy (IST) to beginning of eltrombopag was Me(min-max): 56(12-115), 51(8-94), 1(1-1), 69(37-100) months respectively. The daily dose of eltrombopag for pts was 100-150 mg.

Results. Hematological response are present in 3 out of 5 pts in the 1^st group. Median duration of eltrombopag treatment was 8,5 (3-12) months. It is necessary to note that responding pts were refractory to 2^nd (n=1) or 3^rd (n=2) ATG and transfusion dependence. All pts in the 2^nd group achieve PR (Me duration eltrombopag treatment was 12 months). All pts from 3^rd group achieved granulocytic response, that allowed to recover get out from infections and to hold the 2^nd ATG. However in 1 pt monosomy 7 was detected by FISH in bone marrow after therapy. It was noted that before eltrombopag administration there were not cytogenetic aberrancies but there were myelodysplastic features by flow cytometry (low index of granularity in granulocytes, low HLA-DR expression of monocytes and high CD56 expression in both granulocytes and monocytes) and PNH-clone. After eltrombopag treatment and monosomy 7 detection we performed a FACS sorting and FISH-study for PNH⁺ and PNH^- granulocytes. Monosomy 7 was found in PNH^- but not in PNH⁺ granulocytes. From the 4^th group thrombocytopenia resolved in 1 pt (11 months eltrombopag duration), in over case present threelineage relapse subsequently.

Conclusion. Eltrombopag can be used in pts with long-term ineffective IST and as a bridge to the next step of IST. It is necessary to remain cautious about the earlier development of clonal complications, even in patients from the so-called favorable risk group with the PNH clone.