Case Report: Recurrence of recipient-derived erythropoiesis in hematopoietic stem cell transplant for sickle-cell anemia: multi-lineage chimerism analysis as a tool to distinguish atypical pure red cell aplasia from poor erythroid engraftment

Experience in hematopoietic stem cell transplant (HSCT) as a long-term curative treatment for sickle-cell anemia (SCA) has been gathered over the last 30 years. Sustained engraftment to restore normal erythropoiesis remains the primary aim of HSCT in this disease. Yet, with the increasing use of reduced intensity conditioning as a toxicity-sparing alternative, a significant proportion of transplanted patients develop mixed chimerism. While a myeloid donor chimerism above 20% is deemed sufficient to prevent pain crisis, patients with donor chimerism below 50% can present recurrence of hemolytic features ( 1 ). Although experimental studies have demonstrated the feasibility of chimerism analysis on CD71-positive erythroblasts as well as earlier erythroid precursors such as BFU-E and CFU-GM, their clinical benefit remains debated ( 2 , 3 ). Herein we report the unusual case of a 15 year-old patient transplanted for SCA who developed Pure Red Cell Aplasia (PRCA), followed by the recurrence of hemolytic anemia and rising HbS levels upon reticulocyte recovery. The patient failed to respond to standard treatment with Rituximab and Daratumumab for PRCA, which further raised concern for poor donor erythroid engraftment or secondary graft failure. In this setting, the information supplied by lineage-specific chimerism, particularly B-cell and erythroid progenitor chimerism, which were both predominantly of donor origin, helped distinguishing the two conditions and guide clinical decision-making. The hematological condition of the patient dramatically improved upon donor-derived B-cell recovery and initiation of plasmapheresis. This clinical report makes an argument for lineage-specific chimerism in patients with hemoglobinopathies experiencing recurrence of hemolytic anemia after PRCA.