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Abstract
Aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia and an empty bone marrow. Standard treatments for AA include immunosuppressive therapy and bone marrow transplantation (BMT). BMT is the preferred option for young AA patients with a sibling donor, whereas in older patients or in those to be grafted from an unrelated donor BMT is exploited as second-line treatment. Current results of BMT for AA demonstrate cure rates up to 80 and 70% in BMT from HLA-matched siblings and unrelated donor, respectively, with age and stem cell source largely affecting the outcome. BMT is also a potential treatment option for paroxysmal nocturnal hemoglobinuria, a rare hematological disorder characterized by complement-mediated intravascular hemolytic anemia, thrombophilia and bone marrow failure.
Acknowledgements
The authors wish to thank the Severe Aplastic Anemia Working Party of the EBMT for the continuous update and discussion on the outcome of BMT for AA and PNH in Europe.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Aplastic anemia (AA) is an acquired bone marrow failure with immune-mediated pathophysiology; immunosuppressive treatment (IST) and bone marrow transplantation (BMT) are the two well-established treatment options for AA patients.
IST may result in a response rates as high as 60–70%; however, response may be partial and often require long-term maintenance IST, and relapse occurs in about one-third of cases.
BMT is the standard frontline treatment for AA patients up to 40 years old who have an HLA-identical sibling donor; for older patients, BMT is also the standard second-line treatment in case of failure of immunosuppression.
The standard conditioning regimen for BMT from HLA-identical sibling is CY-200 and anti-thymocyte globulin (ATG); patients of older age may benefit from a fludarabine-based reduced intensity conditioning (Flu-Cy-ATG), possibly including low-dose total body irradiation.
The outcome of unrelated BMT has improved in the past decades, with results similar to those of sibling BMT when a 10/10 (or 8/8) HLA-identical donor is available; thus, BMT even from unrelated donors is the preferred treatment for AA patients <60 years old who fail a first-line immunosuppression course.
The standard conditioning regimen for BMT from unrelated HLA-matched donors includes fludarabine, cyclophosphamide and ATG (Flu-Cy-ATG).
The replacement of ATG in the conditioning regimen with the anti-CD52 monoclonal antibody alemtuzumab seems to result in significantly better outcome, mostly due to reduced graft-versus-host disease rates.
BMT from alternative sources such as cord blood units or HLA haplo-identical donors may be offered to AA patients refractory to two to three immunosuppression courses; recent results from HLA haplo-identical donors seems very promising.
BMT is the only curative option for paroxysmal nocturnal hemoglobinuria (PNH); indications to BMT for PNH include concomitant AA and possibly hemolytic PNH resistant to eculizumab, whereas thrombotic PNH should not be considered an indication due to an elevated transplant-related mortality.
Concomitant regimens for BMT in PNH parallel those of AA, especially in presence of concomitant bone marrow failure; more myeloablative regimens may be considered for patients with ‘florid’ PNH.