富集CD34^+细胞作干细胞移植的临床初步探索

Selected CD34^+ cells transplantation: a primary clinical report

目的 观察富集CD34+的造血干 /祖细胞做肿瘤患者同种异基因造血干细胞移植 (Allo HSCT)和自体移植的临床疗效。观察输注纯化CD34+细胞患者的预后情况。方法 采用磁分选临床型细胞富集仪将表面包被有CD34单抗的磁性微球体系与细胞共同培养 ,特异性结合CD34+细胞。在磁场作用下分别收集CD34+和CD34-组分。完成 2 0例患者CD34+细胞体外纯化富集。其中HLA半相合移植 5例 ,自体移植 15例。结果 纯化后CD34+细胞纯度达 97%以上 ,移植CD34+细胞中位数 5 .72 (0 .15～ 12 .0 )× 10 6,CD34+细胞中位数 3.73(2 .6～ 6 .8)× 10 4 ;CD34-细胞 (CD3、CD4、CD8、CD19)对数去除率 (Log,下同 )为 1.99～ 5 .0。 19例患者移植后随访 11个月 (中位数 ,1～ 2 0 ) ,总体生存13/ 19(例 )。本院 11例中 ,总体生存为 8/ 11(例 ) ,其中HLA半相合 1/ 3(例 ) ,自体移植 7/ 8(例 )。移植后造血重建迅速 ,随访 18个月以上无病生存者 3例中 1例为同种异基因HLA半相合亲属移植 ,2例为肿瘤自体移植。 1例父子间HLA半相合移植 ,白细胞恢复 >1× 10 9/L ,血小板 >2 0× 10 9/L(均为移植后第 13天 )。仅有短暂的I度移植物抗宿主疾病。 2例自体移植病例白细胞恢复 >1× 10 9/L(8～ 2 6d) ,血小板恢复 >2 0× 10 9/L(2 2～ 35d)。

Objective CD34 + is an immunophenotype of hematopoietic stem cells/progenitors. CD34 + cells selection in vitro may deplete T cells 4 5 logs and tumor cells 3 4 logs. It will benefit to mismatched related donor allo transplantation and autologous transplantation of tumor diseases. Methods 19 patients aged 29 (5～52) years were treated by allo ( n =5) or auto PB CD34 + cells transplantation ( n =14). Grafts from fifteen patients with various disorders (3 lymphomas, 6 multiple myelomas, 2 SLE, 1 Sjogren's syndrome, 2 breast cancer and 1 medulloblastoma) and five haploidentical donors for leukemia patients (1 ALL CR2, 2 AML rel, 1 CML CP and 1 MDS RAEB) were isolated using magnetic activated cell sorting (CliniMACS, Milteny Biotech, Germany). Results After separation, purity of CD34 + cells was >97 %. Depletion of CD34 negative cells was extensive: CD3 + 2.6～4.6 logs, CD4 + >5 logs, CD8 + 4.6 > 5 logs, and CD19 + 1.2～3.1 logs. 19 patients who received selected CD34 + cells transplantation (CD34 +CT) were followed up for 11(1～20) months. Overall survival(OS) was 13/19 (68.4%) cases. 1/5 patients with haploidentical transplant had disease free survival for 19 months. 12/14(85.7%) auto CD34 +CT achieved overall survival(OS). Conclusion Selected CD34 + cells transplantation significantly decreases the incidence of >Ⅱ GVHD and depletes tumor cell contamination. This approach may be useful to haploidentical or unrelated donor transplantation. It also benefits autologous transplant in various tumor disorders.