Abstract
We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P=0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P=0.18), and for grades III–IV was 2.6% vs 11.6% (P=0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P=0.002) and extensive 5% vs 23.6% (P=0.01). OS was 74% vs 76% for BM vs PBSCs (P=0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P=0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P=0.005) respectively. In multivariate analysis, aGvHD II–IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1–5.6, P=0.02) and aGvHD III–IV (HR 8.3 CI 3.4–20.2, P<0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients.
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References
Dezern AE, Brodsky RA . Clinical management of aplastic anemia. Expert Rev Hematol 2011; 4: 221–230.
Bacigalupo A, Socié G, Schrezenmeier H, Tichelli A, Locasciulli A, Fuehrer M et al. Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anemia: survival advantage for bone marrow in all age groups. Haematologica 2012; 97: 1142–1148.
Schrezenmeier H, Passweg JR, Marsh JC, Bacigalupo A, Bredeson CN, Bullorsky E et al. Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood 2007; 110: 1397–1400.
Jaime-Perez JC, Ruiz-Arguelles GJ, Gomez-Almaguer D . Haematopoietic stem cell transplantation to treat aplastic anaemia. Expert Opin Biol Ther 2005; 5: 617–626.
Seth T, Kanga U, Sood P, Sharma V, Mishra P, Mahapatra M . Audit of peripheral stem cell transplantation for aplastic anemia in multitransfused infected patients. Transplant Proc 2012; 44: 922–924.
Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.
Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 1997; 97: 855–864.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.
Kanda Y . Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 2013; 48: 452–458.
Bacigalupo A, Socié G, Hamladji RM, Aljurf M, Maschan A, Kyrcz-Krzemien S et al. Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia: an EBMT analysis. Haematologica 2015; 100: 696–702.
Kumar R, Kimura F, Ahn KW, Hu ZH, Kuwatsuka Y, Klein JP et al. Comparing outcomes with bone marrow or peripheral blood stem cells as graft source for matched sibling transplants in severe aplastic anemia across different economic regions. Biol Blood Marrow Transplant 2016; 22: 932–940.
Doney K, Leisenring W, Storb R, Appelbaum FR . Primary treatment of acquired aplastic anemia: outcomes with bone marrow transplantation and immunosuppressive therapy. Seattle Bone Marrow Transplant Team. Ann Intern Med 1997; 126: 107–115.
Scheinberg P, Young NS . How I treat acquired aplastic anemia. Blood 2012; 120: 1185–1196.
Maury S, Bacigalupo A, Anderlini P, Aljurf M, Marsh J, Socié G et al. Improved outcome of patients older than 30 years receiving HLA-identical sibling hematopoietic stem cell transplantation for severe acquired aplastic anemia using fludarabine-based conditioning: a comparison with conventional conditioning regimen. Haematologica 2009; 94: 1312–1315.
George B, Mathews V, Viswabandya A, Kavitha ML, Srivastava A, Chandy M . Fludarabine and cyclophosphamide based reduced intensity conditioning (RIC) regimens reduce rejection and improve outcome in Indian patients undergoing allogeneic stem cell transplantation for severe aplastic anemia. Bone Marrow Transplant 2007; 40: 13–18.
Dulley FL, Vigorito AC, Aranha FJ, Sturaro D, Ruiz MA, Saboya R et al. Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection. Bone Marrow Transplant 2004; 33: 9–13.
Chandy M, Srivastava A, Dennison D, Mathews V, George B . Allogeneic bone marrow transplantation in the developing world: experience from a center in India. Bone Marrow Transplant 2001; 27: 785–790.
George B, Mathews V, Lakshmi KM, Melinkeri S, Sharma A, Viswabandya A et al. The use of a fludarabine-based conditioning regimen in patients with severe aplastic anemia—a retrospective analysis from three Indian centers. Clin Transplant 2013; 27: 923–929.
Acknowledgements
We express our gratitude to Marco Martinez for his kind assistance with the statistical analysis of the data and Sergio Lozano-Rodriguez for his help in reviewing the manuscript. This article was funded by the Servicio de Hematología, Hospital Universitario ‘Dr José Eleuterio González’ de la Facultad de Medicina de la Universidad Autónoma de Nuevo León, Monterrey, México.
Author contributions
AV-M, DG-A, JRN-C, VA-P, VM, GJ, LV-G, AK-A, AB-A and GJR-A conceived the study, executed the statistical analysis and drafted the manuscript; JCJ-P and CHG-A designed the study and contributed to the manuscript; JG, ALB, SS, GB, SG, AR, SY, GK, JA, JMR, GJ, LR, CF, JV-O, EP-M, SG, EG-L, MAH-R, MMG-A, EH-M, MP-I, GR-G and MAGR-E contributed gathering the information and executing the statistical analysis.
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Gómez-Almaguer, D., Vázquez-Mellado, A., Navarro-Cabrera, J. et al. The Latin American experience of allografting patients with severe aplastic anaemia: real-world data on the impact of stem cell source and ATG administration in HLA-identical sibling transplants. Bone Marrow Transplant 52, 41–46 (2017). https://doi.org/10.1038/bmt.2016.212
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DOI: https://doi.org/10.1038/bmt.2016.212
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