Hematopoietic Growth Factors in Aplastic Anemia Patients Treated with Immunosuppressive Therapy-systematic Review and Meta-analysis

Overview

Journal Haematologica

Specialty Hematology

Date 2009 Apr 2

PMID 19336743

Citations 28

Authors

Ronit Gurion

Anat Gafter-Gvili

Mical Paul

Liat Vidal

Isaac Ben-Bassat

Moshe Yeshurun

Ofer Shpilberg

Pia Raanani

Affiliations

Soon will be listed here.

Abstract

Immunosuppressive therapy is the treatment for aplastic anemia patients ineligible for transplantation. The role of hematopoietic growth factors as adjunct to treatment in these patients is unclear. We conducted a systematic review and meta-analysis of randomized controlled trials comparing treatment with immunosuppressive therapy and hematopoietic growth factors to immunosuppressive therapy alone in patients with aplastic anemia. Two reviewers appraised the quality of trials and extracted data. For each trial, results were expressed as relative risks with 95% confidence intervals (CI) for dichotomous data. The addition of hematopoietic growth factors yielded no difference in overall mortality at 100 days, one year and five years [relative risks 1.33 (95% CI 0.56-3.18), relative risks 0.90 (95% CI 0.50-1.63) and relative risks 0.89 (95% CI 0.55-1.46), respectively]. There was no difference in overall hematologic response and in the occurrence of infections. HGF significantly decreased the risk for relapse, relative risks 0.45 (95% CI 0.30-0.68, 3 trials). Hematopoietic growth factors were not associated with higher occurrence of myelodysplastic syndrome and acute myeloid leukemia or paroxysmal nocturnal hemoglobinuria. The addition of hematopoietic growth factors does not affect mortality, response rate or infections occurrence. Therefore, it should not be recommended routinely as an adjunct to the immunosuppressive therapy for patients with aplastic anemia.

Citing Articles

Outpatient subcutaneous alemtuzumab is feasible and safe for aplastic anemia and is associated with high response rates.

da Fonseca A, da Fonseca A, Justino C, Campos de Molla V, Eiko Yamakawa P, Rabelo I Blood Adv. 2024; 9(4):906-912.

PMID: 39693508 PMC: 11876827. DOI: 10.1182/bloodadvances.2024014159.

Aplastic Anemia as a Roadmap for Bone Marrow Failure: An Overview and a Clinical Workflow.

Solimando A, Palumbo C, Pragnell M, Bittrich M, Argentiero A, Krebs M Int J Mol Sci. 2022; 23(19).

PMID: 36233062 PMC: 9569739. DOI: 10.3390/ijms231911765.

Efficacy of combined immunosuppression with or without eltrombopag in children with newly diagnosed aplastic anemia.

Goronkova O, Novichkova G, Salimova T, Kalinina I, Baidildina D, Petrova U Blood Adv. 2022; 7(6):953-962.

PMID: 35446936 PMC: 10027512. DOI: 10.1182/bloodadvances.2021006716.

Chinese Herbal Medicine Therapy Reduces the Risks of Overall and Anemia-Related Mortalities in Patients With Aplastic Anemia: A Nationwide Retrospective Study in Taiwan.

Chiu M, Hsu Y, Chen C, Li T, Chiou J, Tsai F Front Pharmacol. 2021; 12:730776.

PMID: 34690769 PMC: 8531749. DOI: 10.3389/fphar.2021.730776.

Immunosuppression and growth factors for severe aplastic anemia: new data for old questions.

Young D, Dunbar C Haematologica. 2020; 105(5):1170-1171.

PMID: 32358076 PMC: 7193508. DOI: 10.3324/haematol.2020.246512.

References

DerSimonian R, Laird N . Meta-analysis in clinical trials. Control Clin Trials. 1986; 7(3):177-88. DOI: 10.1016/0197-2456(86)90046-2. View

He G, Shao Z, Zhang Y, Liu H, Li K, Song L . [Sequential intensified immunosuppressive therapy combining with hematopoietic growth factors in the treatment of severe aplastic anemia]. Zhonghua Xue Ye Xue Za Zhi. 2002; 22(4):177-81. View

Socie G, Mary J, Schrezenmeier H, Marsh J, Bacigalupo A, Locasciulli A . Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT). Blood. 2006; 109(7):2794-6. DOI: 10.1182/blood-2006-07-034272. View

Symeonidis A, Kouraklis-Symeonidis A, Seimeni U, Galani A, Giannakoulas N, Fragopanagou E . Ticlopidine-induced aplastic anemia: two new case reports, review, and meta-analysis of 55 additional cases. Am J Hematol. 2002; 71(1):24-32. DOI: 10.1002/ajh.10150. View

Gluckman E, Boogaerts M, Briere J, Navarro J, Leverger G, Leporrier M . New approach of treatment of severe aplastic anemia. Cooperative Group on the Treatment of Aplastic Anemia. Bone Marrow Transplant. 1991; 7 Suppl 2:106-7. View

Bacigalupo A, Bruno B, Saracco P, Di Bona E, Locasciulli A, Locatelli F . Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on.... Blood. 2000; 95(6):1931-4. View

Locasciulli A, Arcese W, Locatelli F, Di Bona E, Bacigalupo A . Treatment of aplastic anaemia with granulocyte-colony stimulating factor and risk of malignancy. Italian Aplastic Anaemia Study Group. Lancet. 2001; 357(9249):43-4. DOI: 10.1016/s0140-6736(00)03574-1. View

Storb R, Longton G, Anasetti C, Appelbaum F, Beatty P, Bensinger W . Changing trends in marrow transplantation for aplastic anemia. Bone Marrow Transplant. 1992; 10 Suppl 1:45-52. View

Bacigalupo A, Broccia G, Corda G, Arcese W, Carotenuto M, Gallamini A . Antilymphocyte globulin, cyclosporin, and granulocyte colony-stimulating factor in patients with acquired severe aplastic anemia (SAA): a pilot study of the EBMT SAA Working Party. Blood. 1995; 85(5):1348-53. View

10.

Shao Z, Chu Y, Zhang Y, Chen G, Zheng Y . Treatment of severe aplastic anemia with an immunosuppressive agent plus recombinant human granulocyte-macrophage colony-stimulating factor and erythropoietin. Am J Hematol. 1998; 59(3):185-91. DOI: 10.1002/(sici)1096-8652(199811)59:3<185::aid-ajh2>3.0.co;2-3. View

11.

Gordon-Smith E, Yandle A, Milne A, Speck B, Marmont A, Willemze R . Randomised placebo controlled study of RH-GM-CSF following ALG in the treatment of aplastic anaemia. Bone Marrow Transplant. 1991; 7 Suppl 2:78-80. View

12.

Kojima S, Hibi S, Kosaka Y, Yamamoto M, Tsuchida M, Mugishima H . Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood. 2000; 96(6):2049-54. View

13.

Imashuku S, Hibi S, Bessho F, Tsuchida M, Nakahata T, Miyazaki S . Detection of myelodysplastic syndrome/ acute myeloid leukemia evolving from aplastic anemia in children, treated with recombinant human G-CSF. Haematologica. 2003; 88(11):ECR31. View

14.

Gluckman E, Hann I, Nikiforakis E, Tavakoli F, Bacigalupo A . Results and follow-up of a phase III randomized study of recombinant human-granulocyte stimulating factor as support for immunosuppressive therapy in patients with severe aplastic anaemia. Br J Haematol. 2002; 119(4):1075-82. DOI: 10.1046/j.1365-2141.2002.03947.x. View

15.

Vadhan-Raj S, Broxmeyer H, Hittelman W . Use of granulocyte-macrophage colony-stimulating factor in hematopoietic disorders: biology and nature of response. Semin Hematol. 1992; 29(4 Suppl 3):4-13. View

16.

Brodsky R . Biology and management of acquired severe aplastic anemia. Curr Opin Oncol. 1998; 10(2):95-9. DOI: 10.1097/00001622-199803000-00002. View

17.

Ades L, Mary J, Robin M, Ferry C, Porcher R, Esperou H . Long-term outcome after bone marrow transplantation for severe aplastic anemia. Blood. 2003; 103(7):2490-7. DOI: 10.1182/blood-2003-07-2546. View

18.

Dincol G, Aktan M, Diz-Kucukkaya R, Yavuz S, Nalcaci M, Ozturk S . Treatment of acquired severe aplastic anemia with antilymphocyte globulin, cyclosporin A, methyprednisolone, and granulocyte colony-stimulating factor. Am J Hematol. 2007; 82(9):783-6. DOI: 10.1002/ajh.20954. View

19.

Doney K, Pepe M, Storb R, Bryant E, Anasetti C, Appelbaum F . Immunosuppressive therapy of aplastic anemia: results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high-dose methylprednisolone, and oxymetholone. Blood. 1992; 79(10):2566-71. View

20.

Zheng Y, Liu Y, Chu Y . Immunosuppressive therapy for acquired severe aplastic anemia (SAA): a prospective comparison of four different regimens. Exp Hematol. 2006; 34(7):826-31. DOI: 10.1016/j.exphem.2006.03.017. View