To study the effect of natural killer (NK) cells on graft-versus-host disease (GVHD) after H-2 haploidentical bone marrow transplantation (BMT) in mice. Methods :Murine model of H-2 haploidentical BMT was estab...To study the effect of natural killer (NK) cells on graft-versus-host disease (GVHD) after H-2 haploidentical bone marrow transplantation (BMT) in mice. Methods :Murine model of H-2 haploidentical BMT was established by using Balb/c (H- 2d) mouse as recipient, and Balb/c (H-2d)×C57BL/6 (H-2b) (H-2db) mouse as donor. Lethally irradiated Balb/c (H-2d) mice were transplanted with the bone marrow cells from Balb/c(H-2d)×C57BL/6(H-2b) (H-2db) mice containing donor spleen cells and/or NK cells. GVHD and survival rates were studied by observation of clinical manifestations and pathological changes. Results:In the group of bone marrow +spleen cells, GVHD was induced in 90% mice; but in the group plus with low amount of NK cells, GVHD was induced in 20% mice; and in the group transplanted with high amount of NK cells, GVHD was induced only in 10% mice. Compared to the group transplanted only with BM plus spleen cells, the incidences of GVHD in the latter two groups decreased significantly (P 〈 0.01) and the survival rates at different periods of 15, 30, 45 and 60 days increased obviously (P 〈 0.01). Conclusion: In mouse H-2 haploidentical BMT, alloreactive NK cells can reduce the incidence of GVHD and increase the survival rate.展开更多
Severe aplastic anemia II(SAA-II)progresses from non-severe aplastic anemia(NSAA).The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation(haplo-BMT)in patients ...Severe aplastic anemia II(SAA-II)progresses from non-severe aplastic anemia(NSAA).The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation(haplo-BMT)in patients lacking a human leukocyte antigen(HLA)-matched donor.This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II.Twenty-two patients were included and followed up,and FLU/BU/CY/ATG was used as conditioning regimen.Among these patients,21 were successfully engrafted,19 of whom survived after haplo-BMT.Four patients experienced grade II–IV aGvHD,including two with grade III–IV aGvHD.Six patients experienced chronic GvHD,among whom four were mild and two were moderate.Twelve patients experienced infections during BMT.One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease,and both recovered after rituximab infusion.Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73%after a median follow-up of 42 months,indicating its effectiveness as a salvage therapy.These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.展开更多
文摘To study the effect of natural killer (NK) cells on graft-versus-host disease (GVHD) after H-2 haploidentical bone marrow transplantation (BMT) in mice. Methods :Murine model of H-2 haploidentical BMT was established by using Balb/c (H- 2d) mouse as recipient, and Balb/c (H-2d)×C57BL/6 (H-2b) (H-2db) mouse as donor. Lethally irradiated Balb/c (H-2d) mice were transplanted with the bone marrow cells from Balb/c(H-2d)×C57BL/6(H-2b) (H-2db) mice containing donor spleen cells and/or NK cells. GVHD and survival rates were studied by observation of clinical manifestations and pathological changes. Results:In the group of bone marrow +spleen cells, GVHD was induced in 90% mice; but in the group plus with low amount of NK cells, GVHD was induced in 20% mice; and in the group transplanted with high amount of NK cells, GVHD was induced only in 10% mice. Compared to the group transplanted only with BM plus spleen cells, the incidences of GVHD in the latter two groups decreased significantly (P 〈 0.01) and the survival rates at different periods of 15, 30, 45 and 60 days increased obviously (P 〈 0.01). Conclusion: In mouse H-2 haploidentical BMT, alloreactive NK cells can reduce the incidence of GVHD and increase the survival rate.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81570124 to Jinsong Yan,No.81702683 to Jiajun Xie,No.81773389 to Jing Shao)Science and Technology Innovation Leading Talent Program of Liaoning Province(No.XLYC1902036 to Jinsong Yan)+5 种基金Basic Research on the Application of Dalian Innovation Fund(No.2019J12SN56 to Jinsong Yan)Key R&D projects in Liaoning Province(No.2019JH8/10300027 to Jinsong Yan)Key Project of the Educational Department of Liaoning Province(No.LZ2020003 to Jinsong Yan)the Capital Health Research and Development of Special Project(No.2014-2-5122 to Hengxiang Wang)the Beijing Municipal Science and Technology Project(No.Z151100004015016 to Hengxiang Wang)the Dalian Medical Scientific Research Project(No.1712040 to Yan Yang)。
文摘Severe aplastic anemia II(SAA-II)progresses from non-severe aplastic anemia(NSAA).The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation(haplo-BMT)in patients lacking a human leukocyte antigen(HLA)-matched donor.This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II.Twenty-two patients were included and followed up,and FLU/BU/CY/ATG was used as conditioning regimen.Among these patients,21 were successfully engrafted,19 of whom survived after haplo-BMT.Four patients experienced grade II–IV aGvHD,including two with grade III–IV aGvHD.Six patients experienced chronic GvHD,among whom four were mild and two were moderate.Twelve patients experienced infections during BMT.One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease,and both recovered after rituximab infusion.Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4%±0.73%after a median follow-up of 42 months,indicating its effectiveness as a salvage therapy.These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.