Bolan C D, Leitman S F, Griffith L M, Wesley R A, Procter J L, Stroncek D F, Barrett A J, Childs R W
Department of Transfusion Medicine, Warren Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Blood. 2001 Sep 15;98(6):1687-94. doi: 10.1182/blood.v98.6.1687.
Delayed donor red cell engraftment and pure red cell aplasia (PRCA) are well-recognized complications of major ABO-incompatible hematopoietic stem cell transplantation (SCT) performed by means of myeloablative conditioning. To evaluate these events following reduced-intensity nonmyeloablative SCT (NST), consecutive series of patients with major ABO incompatibility undergoing either NST (fludarabine/cyclophosphamide conditioning) or myeloablative SCT (cyclophosphamide/high-dose total body irradiation) were compared. Donor red blood cell (RBC) chimerism (initial detection of donor RBCs in peripheral blood) was markedly delayed following NST versus myeloablative SCT (median, 114 versus 40 days; P <.0001) and strongly correlated with decreasing host antidonor isohemagglutinin levels. Antidonor isohemagglutinins declined to clinically insignificant levels more slowly following NST than myeloablative SCT (median, 83 versus 44 days; P =.03). Donor RBC chimerism was delayed 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 following myeloablative SCT. Conversion to full donor myeloid chimerism following NST occurred significantly sooner in cases with, compared with cases without, PRCA (30 versus 98 days; P =.008). Cyclosporine withdrawal appeared to induce graft-mediated immune effects against recipient isohemagglutinin-producing cells, resulting in decreased antidonor isohemagglutinin levels and 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 isohemagglutinins. The clinical manifestations of these events are affected by the degree and duration of residual host hematopoiesis.
延迟供体红细胞植入和纯红细胞再生障碍（PRCA）是通过清髓性预处理进行的主要ABO血型不合造血干细胞移植（SCT）的公认并发症。为了评估降低强度的非清髓性SCT（NST）后的这些情况，对连续系列的主要ABO血型不合患者进行了比较，这些患者分别接受了NST（氟达拉滨/环磷酰胺预处理）或清髓性SCT（环磷酰胺/大剂量全身照射）。与清髓性SCT相比，NST后供体红细胞（RBC）嵌合体（外周血中首次检测到供体RBC）明显延迟（中位数分别为114天和40天；P<.0001），并且与宿主抗供体同种血凝素水平降低密切相关。与清髓性SCT相比，NST后抗供体同种血凝素下降到临床无意义水平的速度更慢（中位数分别为83天和44天；P =.03）。NST后14例患者中有9例（64%）供体RBC嵌合体延迟超过100天，14例患者中有4例（29%）发生PRCA，而清髓性SCT后的12例患者均未发生这些情况。与未发生PRCA的病例相比，NST后发生PRCA的病例更快地转变为完全供体髓系嵌合体（30天对98天；P =.008）。停用环孢素似乎诱导了针对受体产生同种血凝素细胞的移植物介导的免疫效应，导致抗供体同种血凝素水平降低和NST后PRCA的缓解。这些数据表明，（1）主要ABO血型不合NST后供体红细胞生成明显延迟是常见的，（2）与宿主抗供体同种血凝素的长期持续存在有关。这些事件的临床表现受残余宿主造血的程度和持续时间的影响。
