Is post-transplant cyclophosphamide a true game-changer in allogeneic transplantation: The struggle to unlearn

Close HLA matching of donors and recipients has been the dogma for successful allogeneic blood or marrow transplantation (BMT), to limit the complications of graft rejection and graft-versus-host disease (GVHD). However, many patients in need, especially those in certain racial and ethnic groups such as African-Americans and Hispanics, are unable to find matches despite increased availability of unrelated donors. Unfortunately, despite many early attempts to develop safe, related haploidentical allogenic BMT, mortality rates exceeding 50% from severe GVHD led most centers to steer away from such transplants by the mid-1990s. However, recent advances based largely on the development of high-dose post-transplant cyclophosphamide GVHD prophylaxis, now yield results with haploidentical related donors that approach those with matched donors. With emerging data that younger donor age may be the most important donor selection criterion, HLA-mismatched donors may even have advantages over matched donors in certain situations. Although the exact role that haploidentical donors should play in donor selection strategies is still being defined, the lack of an HLA-matched donor should no longer ever be an exclusion for allogeneic BMT. Unfortunately, this progress in donor availability has not yet been fully recognized by the medical community. Such a discordance between new advances and their clinical translation highlights that changing standard practice is difficult and takes longer than it should, at least in part because it requires “unlearning” long-standing behaviors.