Perotti C, Torretta L, Locatelli F, Salvaneschi L
Servizio di Immunoematologia e Trasfusione, I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.
Transfus Sci. 1996 Sep;17(3):423-31. doi: 10.1016/0955-3886(96)00025-2.
There is great interest in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation, based on the good results seen with autologous PBSC infusion. Reasonable caution exists regarding the use of allogeneic PBSC for transplantation because of donor toxicities due to rhG-CSF administration and the risk of graft-versus-host-disease (GVHD) in the recipient because of the large number of T-cell infused. We present preliminary data on allogeneic PBSC collections and transplantation in ten patients affected by advanced leukemia (eight patients), severe aplastic anemia (one patient) and sickle cell anemia (one patient). Seven donors were HLA-identical siblings, while the other three were mismatched for three, two and one locus, respectively. All donors received rhG-CSF at a dose of 12 micrograms/kg for a mean of 5 days. Leukaphereses were performed with the aim of collecting a minimum of 5 x 10(6)/kg (recipient's weight) CD 34+ cells. Collection timing was determined by monitoring CD 34+ cells in the donor's peripheral blood from the second day of rhG-CSF therapy. The PBSC collections yielded a mean of 10.05 x 10(8) MNCs/kg and of 10.48 x 10(6) CD 34+ cells/kg (recipient's weight). PBSC were immediately infused after collection in patients given myeloablative therapy. Engraftment was observed in each patient at a mean of 13.2 days for an absolute neutrophil count (ANC) more than 0.5 x 10(9)/L and of 26.5 days for a platelet count of more than 20 x 10(9)/L. Eight patients experienced no or moderate acute GVHD, whereas two patients died of grade 4 GVHD, notwithstanding GVHD prophylaxis with cyclosporine and prednisone. Two other patients died of viral and fungal infections, respectively, despite prophylaxis. The remaining six patients are alive between 58 and 430 days after transplant. Our results document that allogeneic PBSC are capable of engraftment after a myeloablative regimen. Controlled trials are necessary to compare the potential benefits of this approach with the results obtained in allogeneic bone marrow transplantation.
基于自体外周血干细胞(PBSC)输注取得的良好效果,人们对其在异基因移植中的应用产生了浓厚兴趣。由于rhG-CSF给药导致的供体毒性以及受者因输注大量T细胞而发生移植物抗宿主病(GVHD)的风险,在使用异基因PBSC进行移植时需保持合理谨慎。我们展示了10例晚期白血病患者(8例)、严重再生障碍性贫血患者(1例)和镰状细胞贫血患者(1例)进行异基因PBSC采集和移植的初步数据。7名供体为HLA全相合的同胞,而另外3名分别在3个、2个和1个位点不相合。所有供体均接受剂量为12微克/千克的rhG-CSF,平均用药5天。进行白细胞分离术的目的是采集至少5×10⁶/千克(受者体重)的CD34⁺细胞。采集时间通过在rhG-CSF治疗第二天起监测供体外周血中的CD34⁺细胞来确定。PBSC采集的平均结果为每千克受者体重获得10.05×10⁸个单核细胞(MNC)和10.48×10⁶个CD3⁴⁺细胞。接受清髓性治疗的患者在采集后立即输注PBSC。观察到每位患者的中性粒细胞绝对计数(ANC)超过0.5×10⁹/升的平均时间为13.2天,血小板计数超过20×10⁹/升的平均时间为26.5天。8例患者未发生或仅发生中度急性GVHD,而另外2例患者尽管接受了环孢素和泼尼松预防GVHD治疗,仍死于4级GVHD。另外2例患者尽管进行了预防,但分别死于病毒感染和真菌感染。其余6例患者在移植后58至430天存活。我们的结果表明,异基因PBSC在清髓性方案后能够实现植入。有必要进行对照试验,以比较这种方法的潜在益处与异基因骨髓移植所取得的结果。