Maris Michael, Boeckh Michael, Storer Barry, Dawson Monja, White Kristen, Keng Michael, Sandmaier Brenda, Maloney David, Storb Rainer, Storek Jan
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Exp Hematol. 2003 Oct;31(10):941-52. doi: 10.1016/s0301-472x(03)00201-7.
We studied immune reconstitution in 51 recipients of HLA-identical hematopoietic cellular transplant (HCT) after nonmyeloablative conditioning compared to a reference group of 67 recipients after myeloablative conditioning.
Nonmyeloablative conditioning consisted of 2 Gy total-body irradiation+/-fludarabine and postgrafting cyclosporine and mycophenolate mofetil. All patients received G-CSF-mobilized peripheral blood mononuclear cells. Patients were followed with serial assessments of lymphocyte subset counts, antibody levels, virus-induced lymphoproliferation, and limiting-dilution assays for cytomegalovirus (CMV) T helper (T(H)) cells. Rates of infections over the first year after transplant were calculated.
During the first 180 days, absolute lymphocyte subset counts were similar (except higher total and memory B cell counts on day 80 in nonmyeloablative patients). At 1 year, however, total and naïve CD4 counts, and naïve CD8 counts, were higher in myeloablative patients. The levels of antibodies were similar at all time points and after vaccinations. The function of CD4 cells assessed by virus-induced lymphoproliferation was similar. However, the absolute counts of CMV T(H) cells were higher at days 30 and 90 (p=0.002 and p=0.0003, respectively) after nonmyeloablative conditioning. The rates of definite infections were lower for nonmyeloablative patients during the first 90 days, but were higher later. The higher number of CMV-specific T cells days 30 and 90 after nonmyeloablative HCT coincided with a lower rate of CMV infections during that time.
The immunity of nonmyeloablative HCT recipients appears better than the immunity of conventional HCT recipients early, but not late, after HCT.
我们研究了51例接受非清髓性预处理的 HLA 同型造血细胞移植（HCT）受者的免疫重建情况，并与67例接受清髓性预处理的受者参考组进行比较。
非清髓性预处理包括2 Gy 全身照射±氟达拉滨以及移植后环孢素和霉酚酸酯。所有患者均接受粒细胞集落刺激因子动员的外周血单个核细胞。对患者进行淋巴细胞亚群计数、抗体水平、病毒诱导的淋巴细胞增殖以及巨细胞病毒（CMV）辅助性 T（Th）细胞的有限稀释分析的系列评估。计算移植后第一年的感染率。
在最初的180天内，淋巴细胞亚群绝对计数相似（非清髓性患者在第80天的总 B 细胞和记忆 B 细胞计数除外，其较高）。然而，在1年时，清髓性患者的总 CD4 计数、初始 CD4 计数和初始 CD8 计数较高。所有时间点及接种疫苗后的抗体水平相似。通过病毒诱导的淋巴细胞增殖评估的 CD4 细胞功能相似。然而，非清髓性预处理后第30天和第90天的 CMV Th 细胞绝对计数较高（分别为 p = 0.002 和 p = 0.0003）。非清髓性患者在最初90天内明确感染率较低，但之后较高。非清髓性 HCT 后第30天和第90天较高数量的 CMV 特异性 T 细胞与该时间段内较低的 CMV 感染率一致。
非清髓性 HCT 受者的免疫在 HCT 早期似乎优于传统 HCT 受者，但在后期并非如此。
