Delayed donor red cell chimerism and pure red cell aplasia following majorABO-incompatible nonmyeloablative hematopoietic stem cell transplantation

Delayed donor red cell engraftment and pure red cell aplasia (PRCA) are wel l-recognized complications of major ABO-incompatible hematopoietic stem cel l transplantation (SCT) performed by means of myeloablative conditioning. T o evaluate these events following reduced-intensity nonmyeloablative SCT (N ST), consecutive series of patients with major ABO incompatibility undergoi ng either NST (fludarabine/cyclophosphamide conditioning) or myeloablative SCT (cyclophosphamide/high-dose total body irradiation) were compared. Dono r red blood cell (RBC) chimerism (initial detection of donor RBCs in periph eral blood) was markedly delayed following NST versus myeloablative SCT (me dian, 114 versus 40 days; P < .0001) and strongly correlated with decreasin g host antidonor isohemagglutinin levels. Antidonor isohemagglutinins decli ned to clinically insignificant levels more slowly following NST than myelo ablative SCT (median, 83 versus 44 days; P=.03). Donor RBC chimerism was de layed more than 100 days in 9 of 14 (64%) and PRCA occurred in 4 of 14 (29% ) patients following NST, while neither event occurred in 12 patients follo wing myeloablative SCT. Conversion to full donor myeloid chimerism followin g NST occurred significantly sooner in cases with, compared with cases with out, PRCA (30 versus 98 days; P = .008). Cyclosporine withdrawal appeared t o induce graft-mediated immune effects against recipient isohemagglutinin-p roducing cells, resulting in decreased antidonor ischemagglutinin levels an d resolution of PRCA following NST. These data indicate that significantly delayed donor erythropoiesis is (1) common following major ABO-incompatible NST and (2) associated with prolonged persistence of host antidonor isohem agglutinins. The clinical manifestations of these events are affected by th e degree and duration of residual host hematopoiesis. (C) 2001 by The Ameri can Society of Hematology.