Differences in Natural Killer(NK) Reconstitution Between Unmanipulated Haploidentical and HLA Identical Stem Cell Transplantation and Relationship with Citomegalovirus and Graft Versus Host Disease (GVHD). Experience in One Centre in 22 Patients

Introduction: It´s well known that NK cells exert an important role in postransplant immune reconstitution. Their maturation process through the contact with recipient´s bone marrow stromal cells is crucial for the development of their functional capacities. Previous studies showed the relevance of NK alloreactivity in relapse prevention and the influence of NK subpopulations and expression of activating receptors on CMV infection control, antitumor effects, and graft versus host disease (GVHD). Unmanipulated Haploidentical (Haplo) transplantation with postrasplant cyclophosphamide (Cy) is an emerging alternative for patients (pts) with no identical sibling donor with encouraging results. We previously reported preliminary data of NK cell reconstitution in 7 pts in Haplo setting. Our aim is to contrast our previous data in 22 pts comparing with conventional HLA-identical (HLAid) Stem Cell Transplantation (SCT) and to analyse the relationship between NK reconstitution and CMV reactivation and GVHD. Methods: 22 pts received an Haplo SCT and 7 pts an HLAid SCT in Gregorio Marañon Hospital between January 2013 and April 2014. Peripheral blood was used in all cases. Conditioning regimen comprised fludarabine (Flu), Cy and busulfan (Bux) for Haplo and Flu/Bux or Flu/Melphalan for HLAid SCT. Prophylaxis for GVHD consisted of high dose Cy on +3, +4, cyclosporine (CsA) A and mycophenolatemofetil for Haplo and CsA/Methotrexate for HLAid. Table1 show patients characteristics. For analysis of NK reconstitution and receptor expression multi-colour flow cytometry on FC500 and Navios Beckman Coulter® was used. Total NK cells, CD56 intensity and expression of NKG2A, NKp30, Nkp46 and NKG2D was studied at +15, +30, +60, and +90. For comparison between the two groups Mann–Whitney U-test was used. Results: Median NK cells/mm3 on +15 and +30 were significantly lower on Haplo than HLAid group ( 0 (0-5.5) and 28.5 (12.2-96.5) vs 69.5 (55-134) and 276 (151-422); p Conclusions: After Haplo SCT with postransplant Cy NK cell reconstitution seem to be delayed comparing with HLAid sibling SCT, reaching normal levels at +60. As previously reported, we confirm in our series that NK maturation also show a different pattern. In Haplo setting NK cells remains in an immature phenotype with high proportion of NK CD56b and expression of NKG2A much longer than in HLAid pts. Interestingly activating receptors expression, normally linked to maturation is only lower in Haplo pts in +15, but it is similar in both SCT types by day +30 and later, what should translate in appropriate cytotoxic capacity. In Haplo group, those patients with and without CMV reactivation had similar NK cell reconstitution. Patients with GVHD seem to have an impaired early NK reconstitution, but this fact needs to be contrasted. Acknowledgments: Fundación Mutua Madrileña. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.