Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia
LI Jun, ZONG Su-Yu, YIN Zi-Xi, GAO Yang-Yang, LIU Li-Peng, WAN Yang, LAN Yang, GONG Xiao-Wen, ZHU Xiao-Fan
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
Abstract Objective To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA). Methods A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed. Results The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P<0.05). After propensity score matching, there were no significant differences in baseline features between the negative PNH clone and positive PNH clone groups (P>0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P<0.05). The evolution of PNH clone was heterogeneous after IST, and the children with PNH clone showed an increase in the 3-year cumulative incidence rate of aplastic anemia-PNH syndrome (P<0.05). Conclusions SAA children with positive PNH clone at diagnosis tend to have poor response to IST and are more likely to develop aplastic anemia-PNH syndrome.
LI Jun,ZONG Su-Yu,YIN Zi-Xi et al. Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia[J]. CJCP, 2022, 24(3): 303-308.
LI Jun,ZONG Su-Yu,YIN Zi-Xi et al. Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia[J]. CJCP, 2022, 24(3): 303-308.
Narita A, Muramatsu H, Sekiya Y, et al. Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia[J]. Haematologica, 2015, 100(12): 1546-1552. PMID: 26315930. PMCID: PMC4666330. DOI: 10.3324/haematol.2015.132530.
Gargiulo L, Zaimoku Y, Scappini B, et al. Glycosylphosphatidylinositol-specific T cells, IFN-γ-producing T cells, and pathogenesis of idiopathic aplastic anemia[J]. Blood, 2017, 129(3): 388-392. PMID: 27903525. DOI: 10.1182/blood-2016-09-740845.
5 Fattizzo B, Dunlop A, Ireland RM, et al. Prognostic and predictive impact of small PNH clones in a large cohort of patients with myelodysplastic syndromes and aplastic anemia: a single-center experience[J]. Blood, 2018, 132(Suppl_1): 3870. DOI: 10.1182/blood-2018-99-116772.
Kulagin A, Lisukov I, Ivanova M, et al. Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two-centre prospective study[J]. Br J Haematol, 2014, 164(4): 546-554. PMID: 24261566. DOI: 10.1111/bjh.12661.
Najean Y, Haguenauer O. Long-term (5 to 20 years) evolution of nongrafted aplastic anemias. The Cooperative Group for the Study of Aplastic and Refractory Anemias[J]. Blood, 1990, 76(11): 2222-2228. PMID: 2257296. DOI: 10.1182/blood.V76.11.2222.2222.
Narita A, Muramatsu H, Okuno Y, et al. Development of clinical paroxysmal nocturnal haemoglobinuria in children with aplastic anaemia[J]. Br J Haematol, 2017, 178(6): 954-958. PMID: 28643364. DOI: 10.1111/bjh.14790.
Lian Y, Shi J, Nie N, et al. Evolution patterns of paroxysmal nocturnal hemoglobinuria clone and clinical implications in acquired bone marrow failure[J]. Exp Hematol, 2019, 77: 41-50. PMID: 31472171. DOI: 10.1016/j.exphem.2019.08.005.
de Latour RP, Mary JY, Salanoubat C, et al. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories[J]. Blood, 2008, 112(8): 3099-3106. PMID: 18535202. DOI: 10.1182/blood-2008-01-133918.
Ma XR, Wang J, Zhang WG, et al. Comparison of porcine anti-human lymphocyte globulin and rabbit anti-human thymocyte globulin in the treatment of severe aplastic anemia: a retrospective single-center study[J]. Eur J Haematol, 2016, 96(3): 260-268. PMID: 25966958. DOI: 10.1111/ejh.12584.
Tu JK, Pan H, Li RN, et al. PNH clones for aplastic anemia with immunosuppressive therapy: a systematic review and meta-analysis[J]. Acta Haematol, 2021, 144(1): 34-43. PMID: 32877903. DOI: 10.1159/000506387.
Wang B, He B, Zhu YD, et al. The predictive value of pre-treatment paroxysmal nocturnal hemoglobinuria clone on response to immunosuppressive therapy in patients with aplastic anemia: a meta-analysis[J]. Hematology, 2020, 25(1): 464-472. PMID: 33269994. DOI: 10.1080/16078454.2020.1848083.
Yoshida N, Yagasaki H, Takahashi Y, et al. Clinical impact of HLA-DR15, a minor population of paroxysmal nocturnal haemoglobinuria-type cells, and an aplastic anaemia-associated autoantibody in children with acquired aplastic anaemia[J]. Br J Haematol, 2008, 142(3): 427-435. PMID: 18537977. DOI: 10.1111/j.1365-2141.2008.07182.x.
Timeus F, Crescenzio N, Lorenzati A, et al. Paroxysmal nocturnal haemoglobinuria clones in children with acquired aplastic anaemia: a prospective single centre study[J]. Br J Haematol, 2010, 150(4): 483-485. PMID: 20456361. DOI: 10.1111/j.1365-2141.2010.08219.x.
Scheinberg P, Marte M, Nunez O, et al. Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine[J]. Haematologica, 2010, 95(7): 1075-1080. PMID: 20595102. PMCID: PMC2895030. DOI: 10.3324/haematol.2009.017889.
Bat T, Abdelhamid ON, Balasubramanian SK, et al. The evolution of paroxysmal nocturnal haemoglobinuria depends on intensity of immunosuppressive therapy[J]. Br J Haematol, 2018, 182(5): 730-733. PMID: 28804905. PMCID: PMC5812827. DOI: 10.1111/bjh.14862.
Yenerel MN, Muus P, Wilson A, et al. Clinical course and disease burden in patients with paroxysmal nocturnal hemoglobinuria by hemolytic status[J]. Blood Cells Mol Dis, 2017, 65: 29-34. PMID: 28437723. DOI: 10.1016/j.bcmd.2017.03.013.
Socié G, Schrezenmeier H, Muus P, et al. Changing prognosis in paroxysmal nocturnal haemoglobinuria disease subcategories: an analysis of the International PNH Registry[J]. Intern Med J, 2016, 46(9): 1044-1053. PMID: 27305361. DOI: 10.1111/imj.13160.
Lee JW, Peffault de Latour R, Brodsky RA, et al. Effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) with or without aplastic anemia in the International PNH Registry[J]. Am J Hematol, 2019, 94(1): E37-E41. PMID: 30370949. DOI: 10.1002/ajh.25334.
[1]
Shaanxi Provincial Diagnosis and Treatment Center of Kawasaki Disease/Children's
Hospital of Shaanxi Provincial People's Hospital; Beijing Children's Hospital, Capital Medical University; Shanghai
Children's Medical Center; Children's Hospital of Shanghai Jiao Tong University; Xianyang Children's Hospital of
Shaanxi Province; Suzhou Children's Hospital, Suzhou University; Children's Hospital of Chongqing Medical University;
Expert Committee of Advanced Training for Pediatrician, China Maternal and Children's Health Association; Editorial Board of
Chinese Journal of Contemporary Pediatrics. Pediatric expert consensus on the application of glucocorticoids in Kawasaki disease[J]. CJCP, 2022, 24(3): 225-231.
