Eltrombopag Enhances Recovery from Cytopenias Due to Poor Graft Function After Hematopoietic Cell Transplantation

Overview

Journal Blood Cell Ther

Date 2025 Mar 10

PMID 40061175

Authors

Khalid Halahleh

Maram Al-YaGoub

Mohamad Makoseh

Rozan Al-Far

Waleed Dana

Rula Al-Najjar Pharm

Ayat Taqash

Isra Muradi

Maher Sughayer

Husam Abu-Jazar

Affiliations

Soon will be listed here.

Abstract

Introduction: Poor graft function (PrGF) is a serious complication of allogeneic hematopoietic cell transplantation (allo-HCT), and current therapies are only partially effective. Eight published reports on the effect of eltrombopag on PrGF showed encouraging results. This study aimed to assess the safety and efficacy of eltrombopag for the treatment of PrGF after allo-HCT.

Methods: A retrospective study was conducted on 23 patients with PrGF following allo-HCT at the King Hussein Cancer Center (KHCC), Amman, Jordan between January 2013 and December 2023. The patient-, disease-, and transplant-related characteristics were obtained from the KHCC-BMT database.

Results: The median age was 47 years (range, 26-68 years), and 13 patients were female. Fourteen patients received reduced-intensity conditioning, and 14 donors were human-leukocyte antigen (HLA) -identical siblings. Median hemoglobin (Hb) concentration pre-eltrombopag administration was 8.5 g/dL (range: 6-14.2 g/dL), granulocytes 7.1 × 10/L (range: 1.6-85 × 10/L), and platelets 18 × 10/L (range: 6-50 × 10/L). Thirteen patients had platelets < 20 × 10/L, and 15 had reduced megakaryocytes. The median CD34-positive cell dose was 6.10 × 10/kg (range: 2.75-9.78 × 10/kg). Eltrombopag was initiated at a median of 105 day (d) post-transplant (range: 29-800 d). The median weekly dose was 488 mg (range: 350-700 mg), and the median treatment duration was 75 d (range: 5-446 d). In total, 65% of patients (n=15) responded at a median of 30 d (range, 7-122 d). Twelve responders were alive at a median follow-up of 30 months (range: 7.0-122 months) with normal blood counts. The 2-year overall rate was 48% (95% confidence intervals, 27-70%), and seven non-responders died because of relapse. No major adverse events were reported.

Conclusion: Eltrombopag improved peripheral blood counts in patients with PrGF following allo-HCT. Thus, response to eltrombopag was predictable and has a significant effect on survival.

References

Stasia A, Ghiso A, Galaverna F, Raiola A, Gualandi F, Luchetti S . CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2014; 20(9):1440-3. DOI: 10.1016/j.bbmt.2014.05.016. View

Mahat U, Rotz S, Hanna R . Use of Thrombopoietin Receptor Agonists in Prolonged Thrombocytopenia after Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019; 26(3):e65-e73. DOI: 10.1016/j.bbmt.2019.12.003. View

Desmond R, Townsley D, Dumitriu B, Olnes M, Scheinberg P, Bevans M . Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2013; 123(12):1818-25. PMC: 3962161. DOI: 10.1182/blood-2013-10-534743. View

Lee K, Choi S, Lee J, Kim S, Seol M, Lee Y . Failure of trilineage blood cell reconstitution after initial neutrophil engraftment in patients undergoing allogeneic hematopoietic cell transplantation - frequency and outcomes. Bone Marrow Transplant. 2004; 33(7):729-34. DOI: 10.1038/sj.bmt.1704428. View

Liu X, Wu M, Peng Y, Chen X, Sun J, Huang F . Improvement in poor graft function after allogeneic hematopoietic stem cell transplantation upon administration of mesenchymal stem cells from third-party donors: a pilot prospective study. Cell Transplant. 2013; 23(9):1087-98. DOI: 10.3727/096368912X661319. View

Guardiola P, Kuentz M, Garban F, Blaise D, Reiffers J, Attal M . Second early allogeneic stem cell transplantations for graft failure in acute leukaemia, chronic myeloid leukaemia and aplastic anaemia. French Society of Bone Marrow Transplantation. Br J Haematol. 2000; 111(1):292-302. DOI: 10.1046/j.1365-2141.2000.02306.x. View

Vasudevan Nampoothiri R, Kumar R . Eltrombopag: Role in Cytopenias Following Hematopoietic Stem Cell Transplantation. Indian J Hematol Blood Transfus. 2020; 36(2):238-245. PMC: 7229069. DOI: 10.1007/s12288-019-01194-7. View

Yuan C, Boyd A, Nelson J, Patel R, Varela J, Goldstein S . Eltrombopag for Treating Thrombocytopenia after Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019; 25(7):1320-1324. DOI: 10.1016/j.bbmt.2019.01.027. View

Ghobadi A, Fiala M, Ramsingh G, Gao F, Abboud C, Stockerl-Goldstein K . Fresh or Cryopreserved CD34-Selected Mobilized Peripheral Blood Stem and Progenitor Cells for the Treatment of Poor Graft Function after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2017; 23(7):1072-1077. PMC: 5515540. DOI: 10.1016/j.bbmt.2017.03.019. View

10.

Fattizzo B, Levati G, Cassin R, Barcellini W . Eltrombopag in Immune Thrombocytopenia, Aplastic Anemia, and Myelodysplastic Syndrome: From Megakaryopoiesis to Immunomodulation. Drugs. 2019; 79(12):1305-1319. DOI: 10.1007/s40265-019-01159-0. View

11.

Tang C, Chen F, Kong D, Ma Q, Dai H, Yin J . Successful treatment of secondary poor graft function post allogeneic hematopoietic stem cell transplantation with eltrombopag. J Hematol Oncol. 2018; 11(1):103. PMC: 6097332. DOI: 10.1186/s13045-018-0649-6. View

12.

Marotta S, Marano L, Ricci P, Cacace F, Frieri C, Simeone L . Eltrombopag for post-transplant cytopenias due to poor graft function. Bone Marrow Transplant. 2019; 54(8):1346-1353. DOI: 10.1038/s41409-019-0442-3. View

13.

Halahleh K, Arai Y, Gavriilaki E . Post-Transplant Complications. Blood Cell Ther. 2023; 6(1):23-29. PMC: 10266915. DOI: 10.31547/bct-2022-021. View

14.

McHutchison J, Dusheiko G, Shiffman M, Rodriguez-Torres M, Sigal S, Bourliere M . Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med. 2007; 357(22):2227-36. DOI: 10.1056/NEJMoa073255. View

15.

Bittencourt H, Rocha V, Filion A, Ionescu I, Herr A, Garnier F . Granulocyte colony-stimulating factor for poor graft function after allogeneic stem cell transplantation: 3 days of G-CSF identifies long-term responders. Bone Marrow Transplant. 2005; 36(5):431-5. DOI: 10.1038/sj.bmt.1705072. View

16.

Zhao Y, Gao F, Shi J, Luo Y, Tan Y, Lai X . Incidence, Risk Factors, and Outcomes of Primary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019; 25(9):1898-1907. DOI: 10.1016/j.bbmt.2019.05.036. View

17.

Bento L, Bastida J, Garcia-Cadenas I, Garcia-Torres E, Rivera D, Bosch-Vilaseca A . Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of the Spanish Group of Hematopoietic Stem Cell Transplant. Biol Blood Marrow Transplant. 2019; 25(9):1825-1831. DOI: 10.1016/j.bbmt.2019.05.023. View

18.

Halahleh K, Gale R, Dana W, Makoseh M, Saadeh S, Alan W . Therapy of posttransplant poor graft function with eltrombopag. Bone Marrow Transplant. 2020; 56(1):4-6. DOI: 10.1038/s41409-020-0975-5. View

19.

Townsley D, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O . Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med. 2017; 376(16):1540-1550. PMC: 5548296. DOI: 10.1056/NEJMoa1613878. View

20.

Arslan Davulcu E, Soyer N, Vural F . Eltrombopag for the Treatment of Allogeneic Hematopoietic Stem Cell Transplantation-Related Poor Graft Function. Cureus. 2023; 15(9):e44555. PMC: 10544786. DOI: 10.7759/cureus.44555. View