ÖZET
Amaç:
Kalıcı trombositopeni, allojenik kök hücre transplantasyonunun (AKHN) yaygın komplikasyonlarından biridir. AKHN sonrası trombosit engrafman yetersizliğinin tedavisi hala tartışmalıdır. Eltrombopag bu amaçla kullanılan ilaçlardan biridir. Eltrombopag, FDA onaylı oral trombopoietin reseptör agonistidir. AKHN sonrası şiddetli trombositopeni nedeniyle merkezimizde eltrombopag ile tedavi edilen 12 hastanın sonuçlarını ortaya koymayı amaçladık.
Yöntemler:
Kök hücre nakil merkezimizde ocak 2018’den şubat 2020’ye kadar 56 hastaya AKHN yapıldı. Oniki hastada AKHN sonrası kalıcı trombositopeni gelişti. Tüm hastalar eltrombopag aldı.
Bulgular:
AKHN sonrası inatçı trombositopeni gelişen 12 hastanın altısında birincil trombosit engrafman yetersizliği, altısında ise ikincil trombosit engrafman yetersizliği gelişti. Eltrombopag tedavisi sonrası sekiz hasta (%66,7) transfüzyon bağımsızlığına ulaşılırken dört hastada (%33,3) ulaşılamadı. Eltrombopag tedavisinden sonra maksimum trombosit sayısı medyan 118.000 (aralık: 24.000- 253,000)/μL oldu. Eltrombopag başlangıcından trombosit sayısı >50.000/μL olana kadar geçen süre medyan 18 (aralık:14-112) gün idi. Eltrombopag ile medyan tedavi süresi 70 (aralık: 26-180) gün oldu. Yaşayan ve tam trombosit iyileşmesi olan tüm hastalarda eltrombopag kesildi.
Sonuç:
AKHN sonrası kalıcı trombositopeni, yaşamı tehdit eden kanamalara yol açabileceği için tedavi edilmesi gereken bir durumdur.
References
1
Kuzmina Z, Eder S, Bohm A, Pernicka E, Vormittag L, Kalhs P. et al. Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytope- nia or progressive onset type: results of a prospective study. Leukemia 2012;26:746-56.
2
Yamazaki R, Kuwana M, Mori T, Okazaki Y, Kawakami Y, Ikeda Y, et al. Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover. Bone Marrow Transplant 2006;38:377-84.
3
Bielski M, Yomtovian R, Lazarus HM, Rosenthal N. Prolonged isolated thrombocytopenia after hematopoietic stem cell transplantation: mor- phologic correlation. Bone Marrow Transplant 1998;22:1071-6.
4
Bruno B, Gooley T, Sullivan KM, Davis C, Bensinger WI, Storb R, et al. Secondary failure of platelet recovery after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001;7:154-62.
5
Emmons RV, Reid DM, Cohen RL, Meng G,_Young NS, Dunbar CE, et al. Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction. Blood 1996;87:406871.
6
Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL. Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 2009;113:2161-71.
7
Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007;357:2237-47.
8
Wong RSM, Saleh MN, Khelif A, Salama A, Portella MSO, Burgess P, et al. Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study. Blood 2017;130:2527-36.
9
Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, et al. Eltrombopag added to standard immunosuppression for aplastic anemia. N Engl J Med 2017;376:1540-50.
10
Yuan C, Boyd AM, Nelson J, Patel RD, Varela JC, Goldstein SC, et al. Eltrombopag for Treating Thrombocytopenia after Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant 2019;25:1320-4.
11
Tang C, Chen F, Kong D, Ma Q, Dai H, Yin J, et al. Successful treatment of secondary poor graft function post allogeneic hematopoietic stem cell transplantation with eltrombopag. J Hematol Oncol 2018;11:103.
12
Tanaka T, Inamoto Y, Yamashita T, Shigeo F, Okinaka K, Kurosawa S, et al. Eltrombopag for Treatment of Thorombocytopenia after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2016;22:919-24.
13
Bento L, Bastida JM, Garcia I, Garcia E, Rivera D, Bosch A, et al. Thrombopoietin Receptor Agonist for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of the Spanish Group of Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 2019;25:1825-31.
14
Lee KH, Lee JH, Choi SJ, Lee JH, Kim S, Seol M, et al. Failure of trilineage blood cell reconstitution after initial neutrophil engraftment in patients undergoing allogeneic hematopoietic cell transplantation - frequency and outcomes. Bone Marrow Transplant 2004;33:729-34.
15
Woolfrey A, Anasetti C. Allogeneic hematopoietic stem-cell engraftment and graft failure. Pediatr Transplant 1999;3(Suppl 1):35-40.
16
Bittencourt H, Rocha V, Filion A, Ionescu I, Herr AL, Garnier F, et al. 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;36:431-5.
17
Ghobadi A, Fiala MA, Ramsingh G, Gao F, Abboud CN, Stockerl- Goldstein K, et al. 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;23:1072-7.
18
Liu X, Wu M, Peng Y, Chen X, Sun J, Huang F, et al. 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 2014;23:1087-98.
19
Guardiola P, Kuentz M, Garban F, Blaise D, Reiffers J, Attal M, et al. 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;111:292-302.
20
Poon LM, Di Stasi A, Popat U, Champlin RE, Ciurea SO. Romiplostim for delayed platelet recovery and secondary thrombocytopenia following allogeneic stem cell transplantation. Am J Blood Res 2013;3:260-4.
21
Reid R, Bennett JM, Becker M, Chen Y, Milner L, Phillips GL, et al. Use of eltrombopag, a thrombopoietin receptor agonist, in post-transplantation thrombocytopenia.Am J Hematol 2012;87:743-5.
22
Fujimi A, Kamihara Y, Hashimoto A, Kanisava Y, Nakajima C, Hayasaka N et al. Identification of anti-thrombopoietin receptor antibody in prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation treated successfull with eltrombopag. Int J Hematol 2015;102:471-6.
23
Beck JC, Burke MJ, Tolar J. Response of refractory immune thrombocytopenia after bone marrow transplantation to romiplostim. Pediatr Blood Cancer 2010;54:490-1.
24
Calmettes C, Vigouroux S, Tabrizi R, Milpied N. Romiplostim (AMG531, Nplate) for secondary failure of platelet recovery after allo-SCT. Bone Marrow Transplant 2011;46:1587-9.
25
Bollag RJ, Sterett M, Reding MT, Key NS, Cohn CS, Ustun C. Response of complex immune-mediated thrombocytopenia to romiplostim in the setting of allogeneic stem cell transplantation for chronic myelogenous leukemia. Eur J Haematol 2012;89:361-4.
26
DeRemer DL, Katsanevas K, Bradley A, Awan FT. Romiplostim resistance in secondary failure of platelet recovery. J Oncol Pharm Pract 2013;19:369-72.
27
Maximova N, Zanon D, Rovere F, Maestro A, Schillani G, Paparazzo R. Romiplostim for secondary thrombocytopenia following allogeneic stem cell transplantation in children. Int J Hematol 2015;102:626-32.
28
Battipaglia G, Ruggeri A, Brissot E, Mamez AC, Malard F, Belhocine R, et al. Safety and feasibility of romiplostim treatment for patients with persistent thrombocytopenia after allogeneic stem cell transplantation. Bone Marrow Transplant 2015;50:1574-7.
29
Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet 2011;377:393-402.
30
Will B, Kawahara M, Luciano JP, Bruns I, Parekh S, Erickson-Miller CL, et al. Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. Blood 2009;114:3899-908.
