Aplastic anemia (AA), the myelodysplastic syndromes (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) are rare diseases that all result in bone marrow failure—the ineffective formation of circulating blood cells—leading to anemia, bleeding, infection, and death in many cases, even with modern therapies. Once thought of as distinct, these three diseases are now believed to be linked by similar pathophysiologic pathways. Of the three bone marrow failure diseases, MDS currently has the largest number of therapeutic drugs available, although none of them is curative. Much of the current confusion and controversy in MDS treatment stems from the lack of consensus on which therapies to use in which patients, and what realistic outcomes might be.
Pre-transplant conditioning can significantly influence post-transplant outcomes. A strong anti-tumor effect achieved by myeloablative conditioning (MAC) is frequently counterbalanced by higher morbidity and non-relapse mortality, particularly in older adults. On the other hand, reduced intensity conditioning (RIC) is associated with lower post-transplant mortality, but may not be sufficient enough to prevent relapse, particularly in patients with persistent and aggressive malignances.
Although the myelodysplastic syndromes (MDS) are not curable without hematopoietic cell transplant (HCT), advances in non-transplant therapies today offer considerable benefit to our patients. Over the years, prognostic algorithms have been developed and validated and these are useful guides to allow us to more accurately predict the likely trajectory of disease progression in a group of syndromes that have a notorious heterogeneity.