Rodríguez-Luaces Marta, Ferrá Christelle, Martín-Henao Gregorio, Berlanga Juan José, Grañena Albert, Gallardo David
Alloreactivity Unit, Hematology Department, Institut Català d'Oncologia, Hospital Durán i Reynals, L'Hospitalet, Barcelona, Spain.
Eur J Haematol. 2004 Sep;73(3):162-8. doi: 10.1111/j.1600-0609.2004.00278.x.
The incidence of full donor chimerism (full DC) after CD34+ -selected peripheral blood stem cell transplantation (CD34+ -PBSCT) is controversial. Whereas the initial reports suggested a high incidence of full DC (hypothetically because of the high number of CD34+ cells infused) more recent works describe a high incidence of mixed lymphoid chimerism. There are no data concerning the ability of low-dose donor T-lymphocyte add-back on conversion to full DC.
We prospectively monitored the chimerism status of 25 patients undergoing CD34+ -PBSCT and the effect on chimerism of delayed low doses of donor T-cell add-back (TCAB). One, two or three doses of TCAB were administered on days +28 (2 x 10(5) CD3+/kg), +60 (2 x 10(5) CD3+/kg) and +90 (2 x 10(6) CD3+/kg), respectively, when on cyclosporine A prophylaxis.
Incidence of full DC on day +20 was 56%. However, all but two patients progressed to MC. Fifteen patients were scheduled to TCAB. Six patients with initial MC did not convert to full DC after TCAB. Moreover, seven patients with full DC status progressed to mixed chimerism.
Our results indicate that low doses of TCAB administered under cyclosporine A prophylaxis have no effect on the eradication of the recipient cells. We believe that a high dose of CD34+ cells in the grafts of CD34+ -PBSCT is not enough to achieve stable full DC unless a minimum number of CD3+ cells are infused, or more intensified transplant conditioning regimens are employed.
CD34 + 选择的外周血干细胞移植(CD34 + -PBSCT)后完全供体嵌合体(完全DC)的发生率存在争议。尽管最初的报告表明完全DC的发生率很高(假设是由于输注的CD34 + 细胞数量众多),但最近的研究描述了混合淋巴细胞嵌合体的高发生率。目前尚无关于低剂量供体T淋巴细胞回输对转化为完全DC的能力的数据。
我们前瞻性监测了25例接受CD34 + -PBSCT患者的嵌合体状态,以及延迟低剂量供体T细胞回输(TCAB)对嵌合体的影响。分别在第+28天(2×10⁵ CD3⁺/kg)、+60天(2×10⁵ CD3⁺/kg)和+90天(2×10⁶ CD3⁺/kg)给予一、二或三剂TCAB,此时患者接受环孢素A预防。
第+20天时完全DC的发生率为56%。然而,除两名患者外,所有患者均进展为混合嵌合体(MC)。15例患者计划接受TCAB。6例初始为MC的患者在接受TCAB后未转化为完全DC。此外,7例完全DC状态的患者进展为混合嵌合体。
我们的结果表明,在环孢素A预防下给予低剂量的TCAB对清除受体细胞没有影响。我们认为,CD34 + -PBSCT移植物中高剂量的CD34 + 细胞不足以实现稳定的完全DC,除非输注最低数量的CD3⁺细胞,或采用更强的移植预处理方案。