Low-dose Decitabine for Refractory Prolonged Isolated Thrombocytopenia After HCT: a Randomized Multicenter Trial

Overview

Journal Blood Adv

Specialty Hematology

Date 2021 Mar 1

PMID 33646303

Citations 5

Authors

Yaqiong Tang

Jia Chen

Qifa Liu

Tiantian Chu

Tingting Pan

Jianying Liang

Xue Feng He

Feng Chen

Ting Yang

Xiao Ma

Xiaojin Wu

ShaoYan Hu

Xingyu Cao

Xiaohui Hu

Jiong Hu

Yuejun Liu

Jiaqian Qi

Yueping Shen

Changgeng Ruan

Yue Han

Depei Wu

Affiliations

Soon will be listed here.

Abstract

Refractory prolonged isolated thrombocytopenia (RPIT) is an intractable complication after allogeneic hematopoietic cell transplantation (HCT), which often leads to poor prognosis. A clinical study was designed to validate the efficacy and safety of low-dose decitabine for RPIT after HCT and explore the related underlying mechanisms. Eligible patients were randomly allocated to receive 1 of 3 interventions: arm A, low-dose decitabine (15 mg/m2 daily IV for 3 consecutive days [days 1-3]) plus recombinant human thrombopoietin (300 U/kg daily); arm B, decitabine alone; or arm C, conventional treatment. The primary end point was the response rate of platelet recovery at day 28 after treatment. Secondary end points included megakaryocyte count 28 days after treatment and survival during additional follow-up of 24 weeks. Among the 91 evaluable patients, response rates were 66.7%, 73.3%, and 19.4% for the 3 arms, respectively (P < .001). One-year survival rates in arms A (64.4% ± 9.1%) and B (73.4% ± 8.8%) were similar (P = .662), and both were superior to that in arm C (41.0% ± 9.8%; P = .025). Megakaryocytes, endothelial cells (ECs), and cytokines relating to megakaryocyte migration and EC damage were improved in patients responding to decitabine. This study showed low-dose decitabine improved platelet recovery as well as overall survival in RPIT patients after transplantation. This trial was registered at www.clinicaltrials.gov as #NCT02487563.

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References

Wang H, Huang M, Zhao Y, Qi J, Chen C, Tang Y . Recombinant Human Thrombopoietin Promotes Platelet Engraftment and Improves Prognosis of Patients with Myelodysplastic Syndromes and Aplastic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2017; 23(10):1678-1684. DOI: 10.1016/j.bbmt.2017.06.010. View

Dominietto A, Raiola A, Van Lint M, Lamparelli T, Gualandi F, Berisso G . Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol. 2001; 112(1):219-27. DOI: 10.1046/j.1365-2141.2001.02468.x. View

Verdonck L, de Gast G, van Heugten H, Nieuwenhuis H, Dekker A . Cytomegalovirus infection causes delayed platelet recovery after bone marrow transplantation. Blood. 1991; 78(3):844-8. View

NEVO S, SWAN V, Enger C, Wojno K, Bitton R, Shabooti M . Acute bleeding after bone marrow transplantation (BMT)- incidence and effect on survival. A quantitative analysis in 1,402 patients. Blood. 1998; 91(4):1469-77. View

Appelbaum F . Hematopoietic-cell transplantation at 50. N Engl J Med. 2007; 357(15):1472-5. DOI: 10.1056/NEJMp078166. View

Choi J, Ritchey J, Prior J, Holt M, Shannon W, Deych E . In vivo administration of hypomethylating agents mitigate graft-versus-host disease without sacrificing graft-versus-leukemia. Blood. 2010; 116(1):129-39. PMC: 2904576. DOI: 10.1182/blood-2009-12-257253. View

Yamazaki R, Kuwana M, Mori T, Okazaki Y, Kawakami Y, Ikeda Y . Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover. Bone Marrow Transplant. 2006; 38(5):377-84. DOI: 10.1038/sj.bmt.1705444. View

Gore S, Jones C, Kirkpatrick P . Decitabine. Nat Rev Drug Discov. 2006; 5(11):891-2. DOI: 10.1038/nrd2180. View

Han Y, Tang Y, Chen J, Liang J, Ye C, Ruan C . Low-Dose Decitabine for Patients With Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation: A Pilot Therapeutic Study. JAMA Oncol. 2015; 1(2):249-51. DOI: 10.1001/jamaoncol.2014.316. View

10.

Kiel M, Yilmaz O, Iwashita T, Yilmaz O, Terhorst C, Morrison S . SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005; 121(7):1109-21. DOI: 10.1016/j.cell.2005.05.026. View

11.

Wang J, Yi Z, Wang S, Li Z . The effect of decitabine on megakaryocyte maturation and platelet release. Thromb Haemost. 2011; 106(2):337-43. DOI: 10.1160/TH10-11-0744. View

12.

Rowlings P, Przepiorka D, Klein J, Gale R, Passweg J, Henslee-Downey P . IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol. 1997; 97(4):855-64. DOI: 10.1046/j.1365-2141.1997.1112925.x. View

13.

Bruno B, Gooley T, Sullivan K, Davis C, Bensinger W, Storb R . Secondary failure of platelet recovery after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001; 7(3):154-62. DOI: 10.1053/bbmt.2001.v7.pm11302549. View

14.

Adams G, Scadden D . The hematopoietic stem cell in its place. Nat Immunol. 2006; 7(4):333-7. DOI: 10.1038/ni1331. View

15.

Shi J, Zhao Y, Ishii T, Hu W, Sozer S, Zhang W . Effects of chromatin-modifying agents on CD34+ cells from patients with idiopathic myelofibrosis. Cancer Res. 2007; 67(13):6417-24. DOI: 10.1158/0008-5472.CAN-07-0572. View

16.

First L, Smith B, Lipton J, Nathan D, Parkman R, Rappeport J . Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes. Blood. 1985; 65(2):368-74. View

17.

Dietrich S, Falk C, Benner A, Karamustafa S, Hahn E, Andrulis M . Endothelial vulnerability and endothelial damage are associated with risk of graft-versus-host disease and response to steroid treatment. Biol Blood Marrow Transplant. 2012; 19(1):22-7. DOI: 10.1016/j.bbmt.2012.09.018. View

18.

Kopp H, Hooper A, Broekman M, Avecilla S, Petit I, Luo M . Thrombospondins deployed by thrombopoietic cells determine angiogenic switch and extent of revascularization. J Clin Invest. 2006; 116(12):3277-91. PMC: 1679710. DOI: 10.1172/JCI29314. View

19.

Thachil J, Salter I, George J . Complete remission of refractory immune thrombocytopenia (ITP) with a short course of Romiplostim. Eur J Haematol. 2013; 91(4):376-7. DOI: 10.1111/ejh.12165. View

20.

Avecilla S, Hattori K, Heissig B, Tejada R, Liao F, Shido K . Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nat Med. 2004; 10(1):64-71. DOI: 10.1038/nm973. View