Jaiswal Sarita Rani, Zaman Shamsur, Nedunchezhian Murugaiyan, Chakrabarti Aditi, Bhakuni Prakash, Ahmed Margoob, Sharma Kanika, Rawat Sheh, O'donnell Paul, Chakrabarti Suparno
Manashi Chakrabarti Foundation, Kolkata, India; Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
Department of Blood and Marrow Transplantation, Dharamshila Hospital and Research Centre, New Delhi, India.
Cytotherapy. 2017 Apr;19(4):531-542. doi: 10.1016/j.jcyt.2016.12.006. Epub 2017 Jan 25.
We conducted a pilot study on the feasibility of CD56-enriched donor cell infusion after post-transplantation cyclophosphamide (PTCy) for 10 patients with advanced myeloid malignancies undergoing haploidentical peripheral blood stem cell transplantation with cyclosporine alone as graft-versus-host disease (GVHD) prophylaxis and compared the outcome and immune reconstitution with a control group of 20 patients undergoing the same without CD56-enriched donor cell infusion. An early and rapid surge of mature NK cells as well as CD4 T cells and regulatory T cells (Tregs) was noted compared with the control group. KIR of donor phenotype reconstituted as early as day 30 with expression of CD56CD16NKG2AKIR phenotype. None experienced viral or fungal infections, and non-relapse mortality was 10% only. The incidence of grade 2-4 acute GVHD was 50% in the control group with none in the CD56 group (P = 0.01). Only two had de novo chronic GVHD in each group. Relapse occurred in five patients in CD56 group with a median follow-up of 12 months, similar to the control group. Our preliminary data show that CD56 donor cell infusion after PTCy and short-course cyclosporine is feasible with prompt engraftment, rapid reconstitution of CD4T cells, Tregs and NK cells and reduced incidence of acute GVHD.
我们对10例晚期髓系恶性肿瘤患者进行了一项初步研究,这些患者接受了单倍体相合外周血干细胞移植,移植后使用环磷酰胺(PTCy),仅以环孢素预防移植物抗宿主病(GVHD),并将富含CD56的供体细胞输注的可行性与20例未进行富含CD56供体细胞输注的对照组患者的结果和免疫重建情况进行了比较。与对照组相比,观察到成熟NK细胞以及CD4 T细胞和调节性T细胞(Tregs)早期快速增加。供体表型的杀伤细胞免疫球蛋白样受体(KIR)早在第30天就得以重建,伴有CD56CD16NKG2AKIR表型的表达。无一例发生病毒或真菌感染,非复发死亡率仅为10%。对照组2-4级急性GVHD的发生率为50%,而CD56组无一例发生(P = 0.01)。每组仅2例发生新发慢性GVHD。CD56组有5例患者复发,中位随访时间为12个月,与对照组相似。我们的初步数据表明,PTCy和短疗程环孢素后输注CD56供体细胞是可行的,可实现快速植入、CD4T细胞、Tregs和NK细胞的快速重建,并降低急性GVHD的发生率。