Kanda Junya, Ikegame Kazuhiro, Fuji Shigeo, Kurokawa Mineo, Kanamori Heiwa, Fukuda Takahiro, Ohashi Kazuteru, Ishikawa Jun, Ogawa Hiroyasu, Inoue Masami, Ichinohe Tatsuo, Atsuta Yoshiko, Kanda Yoshinobu
Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
Biol Blood Marrow Transplant. 2016 Nov;22(11):2031-2037. doi: 10.1016/j.bbmt.2016.07.020. Epub 2016 Aug 1.
More than 1% of the Japanese population has HLA-homozygous haplotypes. For patients with such haplotypes, HLA-haploidentical family members who have no HLA mismatch in the graft-versus-host direction are readily available donor candidates for hematopoietic cell transplantation (HCT). In this study, the outcomes of patients with homozygous HLA-A, -B, and -DRB1 antigens who received HCT without T cell depletion from a haploidentical related donor with mismatches in the host-versus-graft direction only (hetero-to-homo, n = 78) or from an HLA-matched sibling donor (MSD) (MSD-homo, n = 153) were compared with those in patients with heterozygous haplotypes who received HCT from an MSD (MSD-hetero, n = 7242). Transplant outcomes in the hetero-to-homo group were similar to those in the MSD-hetero group regarding neutrophil engraftment, grades III to IV acute graft-versus-host disease (aGVHD), nonrelapse mortality (NRM), relapse, and overall survival. On the other hand, the incidences of severe aGVHD and NRM in the MSD-homo group were significantly lower than those in the MSD-hetero group (grades III to IV aGVHD: aHR .50, P = .034; NRM: aHR .48, P = .004). In conclusion, patients with HLA-homozygous haplotypes achieved lower GVHD and NRM rates for MSD transplantation than those with HLA-heterozygous haplotypes. When an MSD or an appropriate alternative donor is not available for patients with HLA-homozygous haplotypes who need immediate transplantation, transplantation from a haploidentical donor without T cell depletion is a viable option, given the comparable transplant outcomes for hetero-to-homo HCT and MSD-hetero HCT.
超过1%的日本人口拥有HLA纯合单倍型。对于具有此类单倍型的患者,在移植物抗宿主方向上没有HLA错配的HLA单倍型相合家庭成员是造血细胞移植(HCT)现成的供者候选人。在本研究中,将仅在宿主抗移植物方向上存在错配(异基因到纯合子,n = 78)的单倍型相合相关供者或HLA匹配的同胞供者(MSD)(MSD-纯合子,n = 153)进行非T细胞去除的HCT的HLA-A、-B和-DRB1抗原纯合子患者的结局,与接受MSD进行HCT的杂合单倍型患者(MSD-杂合子,n = 7242)的结局进行了比较。在中性粒细胞植入、III至IV级急性移植物抗宿主病(aGVHD)、非复发死亡率(NRM)、复发和总生存方面,异基因到纯合子组的移植结局与MSD-杂合子组相似。另一方面,MSD-纯合子组中重度aGVHD和NRM的发生率显著低于MSD-杂合子组(III至IV级aGVHD:校正风险比[aHR]0.50,P = 0.034;NRM:aHR 0.48,P = 0.004)。总之,与HLA杂合单倍型患者相比,HLA纯合单倍型患者进行MSD移植时的移植物抗宿主病和NRM发生率更低。对于需要立即移植的HLA纯合单倍型患者,如果没有MSD或合适的替代供者,鉴于异基因到纯合子HCT和MSD-杂合子HCT的移植结局相当,那么来自单倍型相合供者的非T细胞去除移植是一个可行的选择。