Vanstraelen Gaëtan, Baron Frédéric, Willems Evelyne, Bonnet Christophe, Hafraoui Kaoutar, Frère Pascale, Fillet Georges, Beguin Yves
Department of Medicine, Division of Hematology; University of Liege, Liege, Belgium.
Exp Hematol. 2006 Jul;34(7):841-50. doi: 10.1016/j.exphem.2006.04.012.
After allogeneic hematopoietic stem cell transplantation with nonmyeloablative conditioning (NMHCT), many patients experience prolonged anemia and require red blood cell (RBC) transfusions. We enrolled 60 consecutive patients undergoing NMHCT in a phase II trial to determine the optimal utilization of recombinant human erythropoietin (rHuEPO) therapy in this setting.
The first 14 NMHCT recipients did not receive rHuEPO (control group). Nineteen patients were scheduled to start rHuEPO on day 0 (EPO group 2) and 27 patients on day 28 after the transplant (EPO group 1). RHuEPO was administered subcutaneously once weekly at a dose of 500 U/kg/wk with the aim of achieving hemoglobin (Hb) levels of 13 g/dL. The 3 groups were well balanced for major characteristics.
During the first month (p < 0.0001) as well as days 30 to 100 (p < 0.0001) and days 100 to 180 (p < 0.0001), Hb values were higher in patients receiving rHuEPO compared to those not receiving it. However, transfusion requirements were significantly decreased only in the first month in EPO group 2 (p = 0.0169). T-cell chimerism above 60% on day 42 was the best predictor of Hb response (p < 0.0001) or Hb correction (p = 0.0217), but myeloid chimerism above 90% also predicted for Hb response (p = 0.0069). Hb response was also decreased in patients receiving CD8-depleted grafts and increased in the few patients not receiving TBI, but only in univariate analysis.
Anemia after NMHCT is sensitive to rHuEPO therapy, but less so than after conventional allogeneic HCT. RHuEPO decreases transfusion requirements only in the first 30 days posttransplant. T-cell chimerism below 60% on day 42 impaired Hb response, suggesting possible inhibition of donor erythropoiesis by residual recipient lymphocytes. A prospective randomized trial should be performed with rHuEPO starting on the day of transplantation to assess its clinical benefit in terms of transfusion requirements and quality of life.
在接受非清髓性预处理的异基因造血干细胞移植（NMHCT）后，许多患者会经历长期贫血，需要输注红细胞（RBC）。我们在一项II期试验中纳入了60例连续接受NMHCT的患者，以确定在这种情况下重组人促红细胞生成素（rHuEPO）治疗的最佳应用。
前14例NMHCT受者未接受rHuEPO（对照组）。19例患者计划在第0天开始使用rHuEPO（EPO组2），27例患者在移植后第28天开始使用（EPO组1）。rHuEPO每周皮下注射一次，剂量为500 U/kg/周，目标是使血红蛋白（Hb）水平达到13 g/dL。这3组在主要特征方面具有良好的平衡性。
在第一个月（p<0.0001）以及第30至100天（p<0.0001）和第100至180天（p<0.0001），接受rHuEPO的患者的Hb值高于未接受的患者。然而，仅在EPO组2的第一个月输血需求显著降低（p=0.0169）。第42天T细胞嵌合率高于60%是Hb反应（p<0.0001）或Hb校正（p=0.0217）的最佳预测指标，但髓系嵌合率高于90%也可预测Hb反应（p=0.0069）。接受去除CD8的移植物的患者Hb反应也降低，而少数未接受全身照射（TBI）的患者Hb反应增加，但仅在单因素分析中如此。
NMHCT后的贫血对rHuEPO治疗敏感，但不如传统异基因造血干细胞移植后敏感。rHuEPO仅在移植后的前30天降低输血需求。第42天T细胞嵌合率低于60%会损害Hb反应，提示残留的受者淋巴细胞可能抑制供体红细胞生成。应该进行一项前瞻性随机试验，从移植当天开始使用rHuEPO，以评估其在输血需求和生活质量方面的临床益处。
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