Matsuda Y, Hara J, Osugi Y, Fujisaki H, Takai K, Ohta H, Nakanishi K, Tokimasa S, Miyoshi H, Tanaka-Taya K, Yamanishi K, Okada S
Department of Pediatrics, Osaka University School of Medicine, Suita, Japan.
Bone Marrow Transplant. 1998 Feb;21(4):355-60. doi: 10.1038/sj.bmt.1701095.
We examined five children who underwent allogeneic peripheral stem cell transplantation (PSCT) using positively selected CD34+ cells from three or two loci-mismatched donors. CD34+ cells mobilized from peripheral blood were separated by immunomagnetic beads. CD34+ cells at 2.2-6.2 x 10(6)/kg were transplanted into three patients with refractory leukemia, a patient with relapsed medulloblastoma and a patient with Fanconi's anemia following a conditioning regimen which included irradiation, alkylating agents and antithymocyte globulin treatment. The number of infused CD3+ cells included in grafts was 2.3-22.7 x 10(4)/kg. Four patients achieved engraftment and hematopoietic reconstitution (> 5 x 10(8)/l of neutrophils on day 10 or 11). Graft rejection was observed in the patient with Fanconi's anemia, but a rapid engraftment was obtained after second PSCT. Although no prophylactic agents other than ATG (included in the conditioning regimen) were used, greater than grade I acute GVHD was not observed, but limited chronic GVHD was observed in two patients. The two patients with leukemia relapsed on days 103 and 210, respectively, and the patient with medulloblastoma died of disease on day 159. The patient with Fanconi's anemia died of fungal infection. CMV and HHV-6 diseases developed in four and two patients, respectively. Thus, although SCT using positively selected peripheral CD34+ cells may be an alternative approach for overcoming graft rejection and GVHD from HLA- mismatched donors, persistent immune deficiency attributing to extremely low numbers of T cells in grafts can potentially lead to reactivation of herpes viruses.
我们研究了5名接受异基因外周血干细胞移植（PSCT）的儿童，这些移植使用的是来自三个或两个位点不匹配供体的经阳性选择的CD34+细胞。从外周血中动员的CD34+细胞通过免疫磁珠进行分离。将2.2 - 6.2×10⁶/kg的CD34+细胞移植到3例难治性白血病患者、1例复发性髓母细胞瘤患者和1例接受了包括放疗、烷化剂和抗胸腺细胞球蛋白治疗的预处理方案后的范可尼贫血患者体内。移植物中所含输注的CD3+细胞数量为2.3 - 22.7×10⁴/kg。4例患者实现了植入和造血重建（第10天或第11天中性粒细胞>5×10⁸/l）。在范可尼贫血患者中观察到了移植物排斥反应，但在第二次PSCT后迅速实现了植入。尽管除了预处理方案中包含的抗胸腺细胞球蛋白外未使用其他预防药物，但未观察到大于I级的急性移植物抗宿主病（GVHD），但在2例患者中观察到了局限性慢性GVHD。2例白血病患者分别在第103天和第210天复发，髓母细胞瘤患者在第159天死于疾病。范可尼贫血患者死于真菌感染。分别有4例和2例患者发生了巨细胞病毒（CMV）和人疱疹病毒6型（HHV - 6）疾病。因此，尽管使用经阳性选择的外周CD34+细胞进行干细胞移植（SCT）可能是克服来自HLA不匹配供体的移植物排斥反应和GVHD的一种替代方法，但由于移植物中T细胞数量极少导致的持续性免疫缺陷可能会潜在地导致疱疹病毒重新激活。
