A comparison of nonmyeloablative and reduced-intensity conditioning for allogeneic stem-cell transplantation
A comparison of nonmyeloablative and reduced-intensity conditioning for allogeneic stem-cell transplantation
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DOI：
10.1097/01.tp.0000129809.09718.7e
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发表时间：
2004-10-15
期刊：
影响因子：
6.2
通讯作者：
Ringdén, O
中科院分区：
文献类型：
--
作者：
Le Blanc, K;Remberger, M;Ringdén, O
背景。越来越多地用于同种异性丘脑干细胞移植，越来越多地使用了非甲状腺素（NM）调节（NM）调节（RIC）。这种方案尚未被比较。主要终点是移植物抗宿主病（GVHD）。次要终点包括输血，植入和与移植相关的死亡率（TRM）。 NM调节（n = 24）由氟达拉滨和2 gy的总体照射组成，然后用环孢素A（CSA）与霉酚酸酯Mofetil（MMF）进行免疫抑制。 RIC（n = 34）方案由氟达拉滨与Busulfan或环磷酰胺，抗硫代细胞球蛋白和移植后免疫抑制CSA Plus甲氨蝶呤组成。诊断包括血液学恶性肿瘤和实体瘤。捐助者是34个人类白细胞抗原 - 相同的兄弟姐妹和24个无关的捐助者。通过Minisatellites的聚合酶链反应分析了嵌合。 NM组的24个中的6个中的6个发生了移植失败，RIC组的I 34中发生，这是一个显着差异（优势比[OR]，22.6; P = 0.02）。 NM组的白细胞减少症也较少，比RIC组所需的红细胞和血小板输血更少。两组的CD3，CD19和CD45供体嵌合的时间和比例相似。 NM组的II级至IV急性GVHD的累积发生率更高（59％vs. 12％； OR，26.9; P <0.001），但我们发现慢性GVHD累积发生率没有差异（41％VS。 61％）。 NM组的TRM为42％，在RIC患者中为20％（相对危险，11.6； P = 0.03）。结论。使用CSA和MMF进行移植后免疫抑制的NM调节导致白细胞减少症和输血较少，但导致移植失败，急性GVHD和TRM的病例比RIC患者更多。
Background. Nonmyeloablative (NM) conditioning and reduced-intensity conditioning (RIC) are increasingly used for allogeneic hernatopoietic stem-cell transplantation. Such regimens have not been compared.Methods. The primary endpoint was graft-versus-host disease (GVHD). Secondary endpoints included transfusions, engraftment, and transplant-related mortality (TRM). NM conditioning (n = 24) consisted of fludarabine and 2-Gy total-body irradiation followed by immunosuppression with cyclosporine A (CsA) combined with mycophenolate mofetil (MMF). The RIC (n = 34) protocol consisted of fludarabine combined with busulfan or cyclophosphamide, antithymocyte globulin, and posttransplant immunosuppression CsA plus methotrexate. Diagnoses included hematologic malignancies and solid tumors. Donors were 34 human leukocyte antigen-identical siblings and 24 unrelated donors. Chimerism was analyzed by polymerase chain reaction of minisatellites.Results. Graft failure occurred in 6 of 24 in the NM group and in I of 34 in the RIC group, which was a significant difference (odds ratio [OR], 22.6; P = 0.02). The NM group also had less leukopenia and required fewer erythrocyte and platelet transfusions than the RIC group. The time to and proportion of CD3, CD19, and CD45 donor chimerism were similar in both groups. The cumulative incidence of grades II to IV acute GVHD was higher in the NM group (59% vs. 12%; OR, 26.9; P < 0.001), but we found no difference in the cumulative incidence of chronic GVHD (41% vs. 61%). TRM was 42% in the NM group and 20% in the RIC patients (relative hazard, 11.6; P = 0.03).Conclusions. NM conditioning with posttransplant immunosuppression using CsA and MMF resulted in less leukopenia and fewer transfusions, but resulted in more cases of graft failure, acute GVHD, and TRM than in RIC patients.