Maciej Zaucha J, Mielcarek Marco, Takatu Alessandra, Little Marie-Terese, Gooley Theodore, Baker Jennifer, Maloney David G, Sandmaier Brenda M, Maris Michael, Chauncey Thomas, Storb Rainer, Torok-Storb Beverly
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Br J Haematol. 2002 Dec;119(3):740-50. doi: 10.1046/j.1365-2141.2002.03905.x.
We hypothesized that patients undergoing major ABO-incompatible non-myeloablative haematopoietic stem cell transplantation (nm-HSCT) might experience prolonged haemolysis after transplant due to the delayed disappearance of host plasma cells producing anti-donor isohaemagglutinins (HAs). To address this question, we analysed data from 107 consecutive patients transplanted with allogeneic peripheral blood stem cells from human leucocyte antigen-matched (related, n = 84; unrelated, n = 23) donors after non-myeloablative conditioning (200 cGy total body irradiation +/- fludarabine). In total, 23 out of the 107 patients received major or major/minor ABO-incompatible transplants. Red blood cell (RBC) transfusion requirements during the first 120 d post transplant were higher in major ABO-mismatched than in ABO-matched recipients (0.12 vs 0.03 median units RBC concentrate/d, P = 0.04). Two patients developed transient pure red cell aplasia, which had resolved spontaneously by 9 months after transplant. Major ABO incompatibility did not influence rates of engraftment. Patients with sustained engraftment experienced gradual declines of anti-donor HAs, and the estimated median time to reaching IgM and IgG titres of < 1:1 was at least 133 d in evaluable patients, approximately twice longer than reported after myeloablative conditioning. There was a strong correlation between degrees of donor chimaerism in erythroid burst-forming units, granulocyte macrophage colony-forming units and granulocytes, indicating that donor erythroid engraftment, defined by early erythroid progenitors, was as prompt as myeloid engraftment. In conclusion, our data suggest that major ABO-incompatibility is not a barrier to successful non-myeloablative HSCT.
我们推测，接受主要ABO血型不合的非清髓性造血干细胞移植（nm-HSCT）的患者，可能会因产生抗供体异血凝素（HA）的宿主浆细胞延迟消失，而在移植后经历长时间的溶血。为解决这个问题，我们分析了107例连续患者的数据，这些患者在接受非清髓性预处理（200 cGy全身照射+/-氟达拉滨）后，接受了来自人类白细胞抗原匹配（亲属供体，n = 84；非亲属供体，n = 23）供体的异基因外周血干细胞移植。在这107例患者中，共有23例接受了主要或主要/次要ABO血型不合的移植。移植后前120天内，主要ABO血型不匹配的受者红细胞（RBC）输血需求量高于ABO血型匹配的受者（中位数分别为0.12单位RBC浓缩液/天和0.03单位RBC浓缩液/天，P = 0.04）。两名患者发生了短暂的纯红细胞再生障碍，移植后9个月时已自发缓解。主要ABO血型不合不影响植入率。持续植入的患者抗供体HA逐渐下降，在可评估的患者中，达到IgM和IgG滴度<1:1的估计中位时间至少为133天，约为清髓性预处理后报道时间的两倍。红系爆式集落形成单位、粒巨噬细胞集落形成单位和粒细胞中的供体嵌合度之间存在很强的相关性，这表明由早期红系祖细胞定义的供体红系植入与髓系植入一样迅速。总之,我们的数据表明，主要ABO血型不合并非成功进行非清髓性HSCT的障碍。
