Risk Factors Associated with Poor Response to Immunosuppressive Therapy in Acquired Aplastic Anemia: A Meta-analysis of Retrospective Studies

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2020 Apr 8

PMID 32256799

Authors

Jia Wang

Ping Shen

Xiangru Wu

Wenjie Jin

Affiliations

Soon will be listed here.

Abstract

Acquired aplastic anemia (AA) is a rare hematological disease characterized by bone marrow hypocellularity and varying degrees of pancytopenia. Immunosuppressive therapy (IST) is currently one of the first-line treatments for AA; however, unresponsiveness remains a major concern. Although previous studies have suggested several common risk factors for unresponsiveness, there are currently no widely accepted predictors. Therefore, a meta-analysis of clinical trials including information on factors associated with unresponsiveness of AA to IST was performed in the present study. The PubMed, Embase and Cochrane Library databases were searched for clinical studies on AA evaluating the association between risk factors and unresponsiveness to IST. After the factors were defined from the selected studies, the association between these factors and unresponsiveness to IST was analyzed using Review Manager software. A total of 10 studies comprising 1,820 cases were included in the present meta-analysis. The following factors were identified as predictors of unresponsiveness: Age (≥60 years), sex, absolute neutrophil count, severity of the disease, paroxysmal nocturnal hemoglobinuria clone, human leukocyte antigen (HLA)-DR2 and cytogenetic abnormalities (CAs). Among these factors, only age (≥60 years) [odds ratio (OR)=1.65], HLA-DR2 negativity (OR=2.72) and CAs (OR=1.93) exhibited a statistically significant association with unresponsiveness to IST (P=0.006, P=0.04 and P=0.01, respectively). In conclusion, the present meta-analysis revealed that age ≥60 years, HLA-DR2 negativity and CAs are risk factors for unresponsiveness to IST. This result may enable clinicians to select an effective therapeutic scheme for patients with AA and even provide novel clues to the pathogenesis of AA.

References

Saunthararajah Y, Nakamura R, Nam J, Robyn J, Loberiza F, Maciejewski J . HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood. 2002; 100(5):1570-4. View

Afable 2nd M, Tiu R, Maciejewski J . Clonal evolution in aplastic anemia. Hematology Am Soc Hematol Educ Program. 2011; 2011:90-5. DOI: 10.1182/asheducation-2011.1.90. View

Vadasz Z, Haj T, Kessel A, Toubi E . Age-related autoimmunity. BMC Med. 2013; 11:94. PMC: 3616810. DOI: 10.1186/1741-7015-11-94. View

Shallis R, Ahmad R, Zeidan A . Aplastic anemia: Etiology, molecular pathogenesis, and emerging concepts. Eur J Haematol. 2018; 101(6):711-720. DOI: 10.1111/ejh.13153. View

Kearns W, Sutton J, Maciejewski J, Young N, Liu J . Genomic instability in bone marrow failure syndromes. Am J Hematol. 2004; 76(3):220-4. DOI: 10.1002/ajh.20101. View

Peces R, Urra J, de la Torre M . Influence of HLA-DR phenotype on tumor necrosis factor-alpha production in renal-transplant recipients. Nephron. 1995; 71(2):180-3. DOI: 10.1159/000188709. View

Piaggio G, Podesta M, Pitto A, Sessarego M, Figari O, Fugazza G . Coexistence of normal and clonal haemopoiesis in aplastic anaemia patients treated with immunosuppressive therapy. Br J Haematol. 1999; 107(3):505-11. DOI: 10.1046/j.1365-2141.1999.01729.x. View

Marsh J, Kulasekararaj A . Management of the refractory aplastic anemia patient: what are the options?. Hematology Am Soc Hematol Educ Program. 2013; 2013:87-94. DOI: 10.1182/asheducation-2013.1.87. View

Shin S, Lee J . The optimal immunosuppressive therapy for aplastic anemia. Int J Hematol. 2013; 97(5):564-72. DOI: 10.1007/s12185-013-1331-y. View

10.

Kojima S, Ohara A, Tsuchida M, Kudoh T, Hanada R, Okimoto Y . Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children. Blood. 2002; 100(3):786-90. DOI: 10.1182/blood.v100.3.786. View

11.

Ihan O, Beksac M, Arslan O, Ozcan M, Koc H, Akan H . HLA DR2: a predictive marker in response to cyclosporine therapy in aplastic anemia. Int J Hematol. 1997; 66(3):291-5. DOI: 10.1016/s0925-5710(97)00054-6. View

12.

Scheinberg P, Wu C, Nunez O, Young N . Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol. 2008; 144(2):206-16. PMC: 4149225. DOI: 10.1111/j.1365-2141.2008.07450.x. View

13.

Young N . Pathophysiologic mechanisms in acquired aplastic anemia. Hematology Am Soc Hematol Educ Program. 2006; :72-7. DOI: 10.1182/asheducation-2006.1.72. View

14.

den Elzen W, Gussekloo J . Anaemia in older persons. Neth J Med. 2011; 69(6):260-7. View

15.

Andro M, Le Squere P, Estivin S, Gentric A . Anaemia and cognitive performances in the elderly: a systematic review. Eur J Neurol. 2013; 20(9):1234-40. DOI: 10.1111/ene.12175. View

16.

Appelbaum F, Barrall J, Storb R, RAMBERG R, Doney K, Sale G . Clonal cytogenetic abnormalities in patients with otherwise typical aplastic anemia. Exp Hematol. 1987; 15(11):1134-9. View

17.

Scheinberg P, Young N . How I treat acquired aplastic anemia. Blood. 2012; 120(6):1185-96. PMC: 3418715. DOI: 10.1182/blood-2011-12-274019. View

18.

Marsh J, Ball S, Cavenagh J, Darbyshire P, Dokal I, Gordon-Smith E . Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol. 2009; 147(1):43-70. DOI: 10.1111/j.1365-2141.2009.07842.x. View

19.

Sloand E, Yong A, Ramkissoon S, Solomou E, Bruno T, Kim S . Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor. Proc Natl Acad Sci U S A. 2006; 103(39):14483-8. PMC: 1599987. DOI: 10.1073/pnas.0605245103. View

20.

Risitano A . Immunosuppressive therapies in the management of immune-mediated marrow failures in adults: where we stand and where we are going. Br J Haematol. 2010; 152(2):127-40. DOI: 10.1111/j.1365-2141.2010.08439.x. View