Severe Aplastic Anemia and Other Marrow Failure Syndromes
Bone marrow failure syndromes are a class of rare diseases with abnormal or absent hematopoeisis in one or more cell lines, and include acquired or congenital aplastic anemia, Fanconi anemia, and Diamond-Blackfan anemia. Most patients are diagnosed in childhood, mainly by presenting with hematologic findings such as single-cell or pancytopenia, myelodysplastic syndromes, or leukemia, particularly acute myeloid leukemia. [1]
Acquired aplastic anemia is thought to have an autoimmune component in many patients, and immunosuppressive therapy is therefore a typical front-line therapy. Patients with aplastic anemia are classified based on the severity of their marrow aplasia, and those with severe aplastic anemia (SAA) are candidates for allogeneic hematopoietic cell transplantation (HCT). [1-3]
Diamond-Blackfan anemia and Fanconi anemia are rare, genetically and clinically heterogeneous disorders, characterized by red cell aplasia. Many patients eventually develop pancytopenias from these syndromes. Allogeneic HCT offers the only potential cure for both disorders. [1,4] A 2016 study of long-term survival in patients transplanted for Fanconi anemia found that 10- and 15-year probabilities of survival were 90% and 79%, respectively. [5]
Advances
Clinical advances improving the outcomes of allogeneic transplants in patients with bone marrow failure syndromes include:
- Using reduced-intensity fludarabine-based preparative regimens and drastically reducing or eliminating radiotherapy conditioning improves outcomes in Fanconi anemia patients, who are sensitive to DNA damage [1,6]
- Using bone marrow rather than peripheral blood stem cells (PBSCs) in allogeneic HCT for SAA leads to significantly better outcomes [7,8]
- Frontline alternative donor HCT may be a better treatment option than immunosupressive therapy for children and adolescents with SAA who lack an HLA-matched related donor [9]
- Using unrelated donor HCT for Diamond-Blackfan anemia at the onset of bi- or trilineage cytopenia and/or the evolution to myelodysplasia or acute myelogenous leukemia [10]
Outcomes
Improved survival
Review outcomes for allogeneic transplantation in patients with bone marrow failure syndromes below. View additional SAA Outcome slides showing demographic data and transplant trends.
Outcome data in this section have been prepared by the Center for International Blood and Marrow Transplant Research® (CIBMTR®), our research program.
As shown in Figures 1 and 2, survival is significantly better at two years post-transplant for both adult and pediatric patients with SAA transplanted during later time periods compared to patients transplanted during earlier time periods (log-rank p-value <0.001).
Figure 1: Adult Severe Aplastic Anemia Survival Over Time, Unrelated HCT
Download slide "Adult Severe Aplastic Anemia Survival Over Time, Unrelated HCT"
Figure 2: Pediatric Severe Aplastic Anemia Survival Over Time, Unrelated HCT
Download slide "Pediatric Severe Aplastic Anemia Survival Over Time, Unrelated HCT"
Figure 3: Severe Aplastic Anemia Survival, Unrelated HCT, by Age
Download slide "Severe Aplastic Anemia Survival, Unrelated Marrow HCT, by Age"
Figure 4: Pediatric Fanconi Anemia Survival, Unrelated HCT, by Cell Source
Download slide "Pediatric Fanconi Anemia Survival, Unrelated HCT, by Cell Source"
Figure 5: Severe Aplastic Anemia Survival, Allogeneic HCT in Adults, by Donor Type
Download slide "Severe Aplastic Anemia Survival, Allogeneic HCT in Adults, by Donor Type"
Figure 6: Severe Aplastic Anemia Survival, Allogeneic HCT in Pediatric Patients, by Donor Type
Referral Timing Guidelines
These guidelines highlight disease categories that include patients at risk for disease progression and who should be referred for a consultation for transplantation. [11]
Transplant Consultation Guidelines: Severe Aplastic Anemia and Other Marrow Failure Syndromes
(including Fanconi anemia, Diamond-Blackfan anemia, Shwachman-Diamond syndrome and others)
- At diagnosis
Download as slides (PPT)
View complete Referral Timing Guidelines
References
- Alter BP. Inherited bone marrow failure syndromes: considerations pre- and posttransplant. Blood. 2017; 130(21): 2257-2264. Access
- Tolar J, Sodani P, Symons H. Alternative donor transplant of benign primary hematologic disorders. Bone Marrow Transplant. 2015; 50(5): 619-627. Access
- Scheinberg P, Young NS. How I treat acquired aplastic anemia. Blood. 2012; 120(6): 1185-1196. Access
- Smith AR, Wagner JE. Current clinical management of Fanconi anemia. Expert Rev Hematol. 2012; 5(5): 513-522. Access
- Bonfim C, Ribeiro L, Nichele S, et al. Long-term survival, organ function, and malignancy after hematopoietic stem cell transplantation for Fanconi anemia. Biol Blood Marrow Transplant. 2016; 22(7): 1257-1263. Access
- de Latour RP, Porcher R, Dalle J-H, et al. Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: the European Group for Blood and Marrow Transplantation experience. Blood. 2013; 122(26): 4279-4286. Access
- Chu R, Brazauskas R, Kan F, et al. Comparison of outcomes after transplantation of G-CSF-stimulated bone marrow grafts versus bone marrow or peripheral blood grafts from HLA-matched sibling donors for patients with severe aplastic anemia. Biol Blood Marrow Transplant. 2011; 17(7): 1018-1024. Access
- Eapen M, Le Rademacher J, Antin JH, et al. Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia. Blood 2011; 118(9): 2618-2621. Access
- Choi YB, Yi ES, Lee JW, et al. Immunosuppressive therapy versus alternative donor hematopoietic stem cell transplantation for children with severe aplastic anemia who lack an HLA-matched familial donor. Bone Marrow Transplant. 2017; 52(1): 47-52. Access
- Narla A, Vlachos A, Nathan DG. Diamond Blackfan anemia treatment: Past, present, and future. Semin Hematol. 2011; 48(2): 117-123. Access
- NMDP/Be The Match and ASBMT Recommended Timing for Transplant Consultation, 2018. Download (PDF)