AZA Combined With NAC for PIT After HSCT

Summary

Prolonged isolated thrombocytopenia (PIT) that is refractory to conventional treatments has remained a critical complication after allogeneic hematopoietic cell transplantation since decades years ago. Recombinant human thrombopoietin (rhTPO) is the main therapy in clinical practice, but remains low efficiency for PIT. Demethylating drugs have shown thier potential in high-risk myelodysplastic syndromes (MDS) and acte myeloid leukemia (AML). In addition, decitabine has demonstrated its efficacy of over 70% for response rate in treatment for PIT in early clinical trials with elusive mechanism. Preliminary experiments revealed that PIT was associated with abnormality of oxidation microenvironment, and N-Acetyl-L-cysteine (NAC) was the most commonly used antioxidant. Therefore, the investigators have been wondering whether Azacitidine in combination with NAC could improve PIT post HSCT and explore the possible mechanism of it.

Timeline

Start

2021-12-01

Primary completion

2024-06-30

Completion

2026-06-30

Publications

• Background First LR, Smith BR, Lipton J, Nathan DG, Parkman R, Rappeport JM. Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes. Blood. 1985 Feb;65(2):368-74.
• Background Bruno B, Gooley T, Sullivan KM, Davis C, Bensinger WI, Storb R, Nash RA. 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.
• Background Wang H, Huang M, Zhao Y, Qi JQ, Chen C, Tang YQ, Qiu HY, Fu CC, Tang XW, Wu DP, Ruan CG, Han 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 Oct;23(10):1678-1684. doi: 10.1016/j.bbmt.2017.06.010. Epub 2017 Jun 19.
• Background Zhao X, Zhao X, Huo M, Fan Q, Pei X, Wang Y, Zhang X, Xu L, Huang X, Liu K, Chang Y. Donor-Specific Anti-Human Leukocyte Antigen Antibodies Predict Prolonged Isolated Thrombocytopenia and Inferior Outcomes of Haploidentical Hematopoietic Stem Cell Transplantation. J Immunol Res. 2017;2017:1043836. doi: 10.1155/2017/1043836. Epub 2017 Apr 16.
• Background Ramirez P, Brunstein CG, Miller B, Defor T, Weisdorf D. Delayed platelet recovery after allogeneic transplantation: a predictor of increased treatment-related mortality and poorer survival. Bone Marrow Transplant. 2011 Jul;46(7):981-6. doi: 10.1038/bmt.2010.218. Epub 2010 Oct 4.
• Background Tang Y, Chen J, Liu Q, Chu T, Pan T, Liang J, He XF, Chen F, Yang T, Ma X, Wu X, Hu S, Cao X, Hu X, Hu J, Liu Y, Qi J, Shen Y, Ruan C, Han Y, Wu D. Low-dose decitabine for refractory prolonged isolated thrombocytopenia after HCT: a randomized multicenter trial. Blood Adv. 2021 Mar 9;5(5):1250-1258. doi: 10.1182/bloodadvances.2020002790.
• Background Mohyeldin A, Garzon-Muvdi T, Quinones-Hinojosa A. Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell. 2010 Aug 6;7(2):150-61. doi: 10.1016/j.stem.2010.07.007.
• Background Chen S, Su Y, Wang J. ROS-mediated platelet generation: a microenvironment-dependent manner for megakaryocyte proliferation, differentiation, and maturation. Cell Death Dis. 2013 Jul 11;4(7):e722. doi: 10.1038/cddis.2013.253.
• Background Kong Y, Shi MM, Zhang YY, Cao XN, Wang Y, Zhang XH, Xu LP, Huang XJ. N-acetyl-L-cysteine improves bone marrow endothelial progenitor cells in prolonged isolated thrombocytopenia patients post allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2018 Jul;93(7):931-942. doi: 10.1002/ajh.25056. Epub 2018 Feb 24.
• Background Han Y, Tang Y, Chen J, Liang J, Ye C, Ruan C, Wu D. Low-Dose Decitabine for Patients With Thrombocytopenia Following Allogeneic Hematopoietic Stem Cell Transplantation: A Pilot Therapeutic Study. JAMA Oncol. 2015 May;1(2):249-51. doi: 10.1001/jamaoncol.2014.316. No abstract available.
• Background Zhou H, Hou Y, Liu X, Qiu J, Feng Q, Wang Y, Zhang X, Min Y, Shao L, Liu X, Li G, Li L, Yang L, Xu S, Ni H, Peng J, Hou M. Low-dose decitabine promotes megakaryocyte maturation and platelet production in healthy controls and immune thrombocytopenia. Thromb Haemost. 2015 May;113(5):1021-34. doi: 10.1160/TH14-04-0342. Epub 2015 Jan 8.

Drugs

Indications