In younger patients with Aplastic Anemia)AA), the standard conditioning proposed by the Working Party on SAA (WPSAA) is cyclophosphamide 50 mg/kg 32 × 4 + ATG. This regimen is nonmyeloablative and highly immunosuppressive to prevent graft rejection and GVHD. Often ATG(Thymogen) is also added. The benefit of adding ATG to cyclophosphamide is unclear, because a recently published prospective randomized clinical trial (RCT) from CIBMTR showed no significant benefit in terms of graft rejection, GVHD, and survival rates, compared with cyclophosphamide alone. Raw unadjusted data, from the EBMT database, however, show a slightly superior 10-year survival of 85% versus 75% when ATG is used as part of the conditioning regimen in sibling donor transplantation.
Patients older then 30 years of age, do less well with allogeneic transplantation because they tolerate GVHD less well. There is some support for using fludarabine, a more immunosupressive drug, for such patients. Fludarabine based conditioning regimen may reduce the negative impact of age in older patients receiving an HLA-identical sibling stem cell transplant Alemtuzumab is a new drug that has been studied and that may also decrease the risk of Graft versus Host Disease. A recent European retrospective review of the combination of Fludarabine, cyclophosphamide and antithymocyte globulin(FCA), with or without low dose total body irradiation, concluded that TBI might have a role. The overall survival was quite comparable for the two regimens, though significant differences were found following more detailed analysis of subgroups. FCA conditioning regimen seems suitable for very young patients with well-matched donors; in other settings the addition of TBI 2 Gy to the FCA regimen seems to offer a better chance of cure, in keeping with results of other recent studies
There is no comparative information for any specific conditioning regimen in young adults with Aplastic Anemia. FCA is as well supported as other alternatives. For that reason, since stem cell transplantation is well established for Aplastic Anemia and the conditioning regimens are a part of this established procedure, the FCA regimen should not be considered Experimental or Investigational and it is medically necessary. The evidence for TBI is weak for young patients and TBI is experimental and it is not medically necessary.
Jakob R. Passweg and Judith C.W. Marsh Aplastic Anemia: First-line Treatment by Immunosuppression and Sibling Marrow Transplantation
ASH Education Book December 4, 2010 vol. 2010 no. 1 36-42
Maury S, Bacigalupo A, Anderlini P, et al.(2009) 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 94:1312–1315.
Marsh, et al. Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anemia Blood 2011 118:2351-2357;
Andrea Bacigalupo et al, Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA working party haematol June 1, 2010 vol. 95 no. 6 976-982
- Guideline] Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan. 172 (2):187-207.
- [Guideline] Barone A, Lucarelli A, Onofrillo D, Verzegnassi F, Bonanomi S, et al. Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP). Blood Cells Mol Dis. 2015 Jun. 55 (1):40-7.
Read the Layperson version here.