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Haematologica 2022 Volume 107(1):126-133
Predicting response of severe aplastic anemia to immunosuppression combined with eltrombopag
Yoshitaka Zaimoku,1 Bhavisha A. Patel,1 Ruba Shalhoub,2 Emma M. Groarke,1 Xingmin Feng,1 Colin O. Wu2 and Neal S. Young1
1Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health and 2Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
ABSTRACT
Pretreatment blood counts, particularly an absolute reticulocyte count ≥25×109/L, correlate with response to immunosuppressive therapy in severe aplastic anemia. In recent trials, eltrombopag combined with standard immunosuppressive therapy yielded superior responses than those to immunosuppressive therapy alone. Our single institution retrospective study aimed to elucidate whether historical pre- dictors of response to immunosuppressive therapy alone were also asso- ciated with response to immunosuppressive therapy plus eltrombopag. We sought correlations of blood counts, thrombopoietin levels and the presence of paroxysmal nocturnal hemoglobinuria clones with both overall and complete responses in 416 patients with severe aplastic ane- mia, aged 2-82 years (median, 30 years), initially treated with immuno- suppressive therapy plus eltrombopag between 2012 and 2019 (n=176) or with immunosuppressive therapy alone between 1999 and 2010 (n=240). Compared to non-responders, patients in the group of overall responders to immunosuppressive therapy plus eltrombopag had signif- icantly higher pretreatment absolute reticulocyte counts, higher neu- trophil counts and reduced thrombopoietin levels, as also observed for the group treated with immunosuppressive therapy alone. Addition of eltrombopag markedly improved the overall response in subjects with an absolute reticulocyte count between 10-30×109/L from 60% (54 of 90) to 91% (62 of 68). Absolute lymphocyte count correlated with complete response in the groups treated with immunosuppressive therapy with or without eltrombopag, especially in adolescents aged ≥10 years and adults, but the correlation was reversed in younger children. Platelet count and the presence of a paroxysmal nocturnal hemoglobinuria clone did not correlate with responses to immunosuppressive therapy. Blood counts remain the best predictors of response to nontransplant therapies in severe aplastic anemia. Addition of eltrombopag to immunosuppres- sive therapy shifted patients with a lower absolute reticulocyte count into a better prognostic category.
Introduction
Immune aplastic anemia (AA), characterized by T-cell-mediated destruction of hematopoietic stem and progenitor cells, is successfully treated with hematopoi- etic stem cell transplantation (HSCT) or immunosuppressive therapy (IST).1 HSCT is preferred for severe AA (SAA) in children and young adults aged ≤40 years, if an HLA-matched sibling donor is available, as it is usually a curative option and has acceptable toxicities. Most adult patients undergo IST since transplantation-relat- ed mortality increases with age.2 IST may result in incomplete hematologic recov- ery, relapse, or clonal evolution to a myeloid malignancy. Standard IST has been established as horse antithymocyte globulin (hATG) plus cyclosporine, to which 60-70% of patients respond with clinically meaningful hematologic improvement. Experimental clinical protocols conducted at our institution using rabbit ATG, alemtuzumab, cyclophosphamide, or with the addition to standard treatment of
Bone Marrow Failure
Correspondence:
YOSHITAKA ZAIMOKU
zaimokuyoshitaka@gmail.com
Received: January 24, 2021. Accepted: April 2, 2021. Pre-published: April 29, 2021.
https://doi.org/10.3324/haematol.2021.278413 ©2022 NIH
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