Pure red cell aplasia after major or bidirectional ABO incompatible hematopoietic stem cell transplantation: to treat or not to treat, that is the question

Daratumumab may be the most effective treatment for post-engraftment pure red cell aplasia due to persistent anti-donor isohemagglutinins after major ABO-mismatched allogeneic transplantation

“…Among the latter, pure red blood cell aplasia (PRCA) due to persistent anti-donor hemagglutinins in the setting of major ABO-mismatched transplantation is one of the most difficult to manage by most clinicians. We thus welcomed the two splendid manuscripts published concomitantly in the April issues of Bone Marrow Transplantation by Marco-Ayala et al [ 1 ] and British Journal of Haematology by Longval et al [ 2 ]. The manuscript by Marco-Ayala et al is the most extensive review on all published articles on PRCA, covering its incidence, risk factors, heterogeneous natural history, and the numerous treatments tested.…”

“…As emphasized by Marco-Ayala et al [ 1 ] and Longval et al [ 2 ], it is difficult for clinicians to know when PRCA requires treatment beyond transfusions or simply requires patience since spontaneous resolution may occur within few weeks. This explains why most patients are treated many months after alloHSCT, often having tried numerous other treatments and having developed severe iron overload.…”

“…This explains why most patients are treated many months after alloHSCT, often having tried numerous other treatments and having developed severe iron overload. However, from all these reports and the current state of knowledge one can conclude the following: The most important risk factor for PRCA and its duration beyond 2–3 months post-alloHSCT is a pre-transplant titer of IsoHG > 1:64 [ 1 , 2 ]. PRCA has a “biomarker”, since the titers of IsoHG must progressively decrease until they disappear.…”

“…In other words, therapeutic intervention would ideally be done when we can exclude the mere presence of residual pre-alloHSCT host IsoHG which simply take time to disappear (first 2–3 months) AND suspect that there are persistent host IsoHG-producing plasma cells. In this respect, the median time to IsoHG disappearance in patients who do not develop prolonged PRCA is around 60 days, while it is beyond 90 days in prolonged PRCA [ 1 , 2 , 10 , 11 ]. GVHD can have a strong graft-vs.-plasma cell effect and is a major predictor of disappearance of IsoHG and recovery from PRCA [ 1 , 2 , 10 , 11 ].…”

“…In this respect, the median time to IsoHG disappearance in patients who do not develop prolonged PRCA is around 60 days, while it is beyond 90 days in prolonged PRCA [ 1 , 2 , 10 , 11 ]. GVHD can have a strong graft-vs.-plasma cell effect and is a major predictor of disappearance of IsoHG and recovery from PRCA [ 1 , 2 , 10 , 11 ]. Since both of our patients developed cGVHD, we expected remission of their PRCA, but this did not occur, prompting a therapeutic intervention.…”