Cornelissen Jan J, van der Holt Bronno, Petersen Eefke J, Vindelov Lars, Russel Charlotte A, Höglund Martin, Maertens Johan, Schouten Harry C, Braakman Eric, Steijaert Monique M C, Zijlmans Mark J M, Slaper-Cortenbach Ineke, Boogaerts Marc A, Löwenberg Bob, Verdonck Leo F
Department of Hematology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Exp Hematol. 2003 Oct;31(10):855-64. doi: 10.1016/s0301-472x(03)00195-4.
Peripheral blood progenitor cells (PBPC) have been established as an alternative source of hematopoietic stem cells for allogeneic transplantation, but an increased incidence of both acute and chronic graft-vs-host disease (GVHD) has become apparent. We performed a prospective randomized trial comparing bone marrow transplantation (BMT) vs PBPC transplantation (PBPCT) using CD34(+) selection for T-cell depletion (TCD) in both study arms.
Between January 1996 and October 2000, 120 patients with a diagnosis of acute leukemia, myelodysplasia, multiple myeloma, or lymphoma were randomized to receive either filgrastim-mobilized PBPC or BM from HLA-identical sibling donors after standard high-dose chemoradiotherapy. Patient characteristics did not differ between study arms.
Recipients of PBPC received more CD3(+) T cells (median: 3.0 vs 2.0 x 10(5)/kg, p<0.0001) and more CD34(+) cells (median: 3.6 vs 0.9 x 10(6)/kg, p<0.0001). Neutrophil and platelet recoveries occurred significantly faster after PBPCT. The cumulative incidence of acute GVHD grades II-IV was 37% after BMT vs 52% after PBPCT and was most significantly (p=0.007) affected by the number of CD3(+) T cells in the graft. Acute GVHD appeared strongly associated with increased treatment-related mortality (TRM) in a time-dependent analysis. Higher numbers of CD34(+) cells were associated with less TRM. With a median follow-up of 37 months (range: 12-75), overall survival at 4 years from transplantation was 60% after BMT and 34% for recipients of PBPCT (p=0.04), which difference was largely due to increased GVHD and TRM in PBPC recipients receiving T-cell dosages greater than 2 x 10(5)/kg.
Outcome following T cell-depleted PBPCT critically depends on the number of CD3(+) T cells, whereby high T-cell numbers may blunt a favorable effect of higher CD34(+) cell numbers.
外周血祖细胞（PBPC）已被确立为异基因移植中造血干细胞的替代来源，但急慢性移植物抗宿主病（GVHD）的发病率均有所增加。我们进行了一项前瞻性随机试验，比较骨髓移植（BMT）与PBPC移植（PBPCT），两个研究组均采用CD34(+)选择法进行T细胞清除（TCD）。
1996年1月至2000年10月期间，120例诊断为急性白血病、骨髓增生异常综合征、多发性骨髓瘤或淋巴瘤的患者被随机分配，在标准大剂量放化疗后接受非格司亭动员的PBPC或来自 HLA 相同同胞供体的骨髓。研究组之间的患者特征无差异。
PBPC接受者接受了更多的CD3(+) T细胞（中位数：3.0对2.0×10(5)/kg，p<0.0001）和更多的CD34(+)细胞（中位数：3.6对0.9×10(6)/kg，p<0.0001）。PBPCT后中性粒细胞和血小板恢复明显更快。BMT后II-IV级急性GVHD的累积发生率为37%，PBPCT后为52%，且最显著地（p=0.007）受移植物中CD3(+) T细胞数量的影响。在一项时间依赖性分析中，急性GVHD似乎与治疗相关死亡率（TRM）增加密切相关。较高数量的CD34(+)细胞与较低的TRM相关。中位随访37个月（范围：12-75个月），移植后4年BMT后的总生存率为60%，PBPCT接受者为34%（p=0.04），这种差异主要是由于接受T细胞剂量大于2×10(5)/kg的PBPC接受者中GVHD和TRM增加。
T细胞清除的PBPCT后的结果严重取决于CD3(+) T细胞的数量，因此高T细胞数量可能会削弱较高CD34(+)细胞数量的有利影响。
