Kurtzberg J, Laughlin M, Graham M L, Smith C, Olson J F, Halperin E C, Ciocci G, Carrier C, Stevens C E, Rubinstein P
Pediatric Bone Marrow Transplant Program, Duke University Medical Center, Durham, NC 27710, USA.
N Engl J Med. 1996 Jul 18;335(3):157-66. doi: 10.1056/NEJM199607183350303.
Transplantation of bone marrow from unrelated donors is limited by a lack of HLA-matched donors and the risk of graft-versus-host disease (GVHD). Placental blood from sibling donors can reconstitute hematopoiesis. We report preliminary results of transplantation using partially HLA-mismatched placental blood from unrelated donors.
Twenty-five consecutive patients, primarily children, with a variety of malignant and non-malignant conditions received placental blood from unrelated donors and were evaluated for hematologic and immunologic reconstitution and GVHD. HLA matching was performed before transplantation by serologic typing for class I HLA antigens and low-resolution molecular typing for class II HLA alleles. In donor-recipient pairs who differed by no more than one HLA antigen or allele, high-resolution class II HLA typing was done retrospectively. Fordonor-recipient pairs who were mismatched for two HLA antigens or alleles, high-resolution typing was used prospectively to select the best match for HLA-DRB1.
Twenty-four of the 25 donor-recipient pairs were discordant for one to three HLA antigens. In 23 of the 25 transplant recipients, the infused hematopoletic stem cells engrafted. Acute grade III GVHD occurred in 2 of the 21 patients who could be evaluated, and 2 patients had chronic GVHD. In vitro proliferative responses of T cells and B cells to plant mitogens were detected 60 days after transplantation. With a median follow-up of 12 1/2 months and a minimal follow-up of 100 days, the overall 100-day survival rate among these patients was 64 percent, and the overall event-free survival was 48 percent.
HLA-mismatched placental blood from unrelated donors is an alternative source of stem cells for hematopoietic reconstitution in children.
无关供者骨髓移植受到缺乏HLA匹配供者以及移植物抗宿主病(GVHD)风险的限制。同胞供者的胎盘血能够重建造血功能。我们报告了使用无关供者部分HLA不匹配的胎盘血进行移植的初步结果。
连续25例患者,主要为儿童,患有各种恶性和非恶性疾病,接受了无关供者的胎盘血,并对其进行了血液学和免疫学重建以及GVHD评估。移植前通过血清学分型检测I类HLA抗原,通过低分辨率分子分型检测II类HLA等位基因进行HLA配型。在相差不超过一个HLA抗原或等位基因的供受者对中,回顾性地进行了高分辨率II类HLA分型。对于相差两个HLA抗原或等位基因的供受者对,前瞻性地使用高分辨率分型来选择HLA-DRB1的最佳匹配。
25对供受者对中有24对在一至三个HLA抗原上不一致。25例移植受者中有23例输注的造血干细胞植入。在21例可评估的患者中,2例发生了急性III级GVHD,2例发生了慢性GVHD。移植后60天检测到T细胞和B细胞对植物有丝分裂原的体外增殖反应。中位随访时间为12.5个月,最短随访时间为100天,这些患者的总体100天生存率为64%,无事件生存率为48%。
无关供者HLA不匹配的胎盘血是儿童造血重建干细胞的替代来源。