Aversa Franco, Reisner Yair, Martelli Massimo F
Department of Hematology, University of Perugia, Perugia, Italy.
Blood Cells Mol Dis. 2004 Nov-Dec;33(3):294-302. doi: 10.1016/j.bcmd.2004.08.021.
Since 75% of patients with high-risk acute leukemia do not have a human leukocyte antigen (HLA)-identical sibling, alternative sources for hematopoietic stem cell transplantation (HSCT) are matched unrelated donors (MUD), unrelated umbilical cord blood (UD-UCB) and one HLA haplotype mismatched family members (haploidentical). The chance of finding a suitable donor in the international voluntary donor registries is limited by frequency of the HLA phenotype and the time required to identify the right donor from a potential panel, to establish eligibility and to harvest the cells. In adult MUD recipients, event-free survival ranges up to 50% and refers only to patients who undergo transplant, without taking into account those who do not find a donor. Umbilical cord blood offers the advantages of easy procurement, the absence of risks to donors, the reduced risk of transmitting infections, immediate availability of cryopreserved samples and acceptance of mismatches at two of the six antigens. Although UD-UCB transplantation is a viable option for children, it is seldom considered for adults. The great divergency between body weight and the number of hematopoietic cells in a standard cord blood unit, particularly if associated with a two-antigen mismatch, increases the risk of graft failure and delays hematopoietic reconstitution. Work on full-haplotype mismatched transplants has been proceeding for over 20 years. Originally, outcome in leukemia patients was disappointing because of high incidence of severe graft-vs.-host disease in T-replete transplants and high rejection rates in T-cell-depleted transplants. The breakthrough came with the use of a megadose of T-cell-depleted progenitor cells after a high-intensity conditioning regimen. Treating end-stage patients inevitably confounded clinical outcome in the early pilot studies. Today, high-risk acute leukemia patients are treated at less advanced stages of disease, receive a reasonably well tolerated conditioning regimen, and benefit from advances in post-transplant immunological reconstitution. All these factors contribute to markedly reduce transplant-related mortality. Overall, event-free survival and transplant-related mortality compare favorably with reports from unrelated matched transplants. T-cell-depleted megadose stem cell transplant from a mismatched family member, who is immediately available, can be offered as a viable option to candidates with high-risk acute leukemias.
由于75%的高危急性白血病患者没有人类白细胞抗原（HLA）相匹配的同胞，造血干细胞移植（HSCT）的替代来源包括匹配的无关供者（MUD）、无关脐血（UD-UCB）以及一个HLA单倍型不匹配的家庭成员（单倍型相合）。在国际自愿捐献者登记处找到合适供者的机会受到HLA表型频率以及从潜在供者库中识别合适供者、确定资格和采集细胞所需时间限制。在成年MUD受者中，无事件生存率高达50%，且仅指接受移植的患者，未考虑那些未找到供者的患者。脐血具有易于采集、对供者无风险、感染传播风险降低、冷冻保存样本可立即获得以及可接受六个抗原中两个抗原不匹配的优点。虽然UD-UCB移植对儿童来说是一个可行的选择，但很少考虑用于成人。标准脐血单位中体重与造血细胞数量之间的巨大差异，特别是如果与两个抗原不匹配相关，会增加移植物失败的风险并延迟造血重建。全单倍型不匹配移植的研究已经进行了20多年。最初，白血病患者的结果令人失望，因为在富含T细胞的移植中严重移植物抗宿主病发生率高，而在T细胞去除的移植中排斥率高。高强度预处理方案后使用大剂量T细胞去除的祖细胞带来了突破。在早期的试点研究中，治疗终末期患者不可避免地混淆了临床结果。如今，高危急性白血病患者在疾病较早期阶段接受治疗，接受耐受性较好的预处理方案，并受益于移植后免疫重建的进展。所有这些因素都有助于显著降低移植相关死亡率。总体而言，无事件生存率和移植相关死亡率与无关匹配移植的报告相比具有优势。来自不匹配家庭成员的T细胞去除大剂量干细胞移植可立即获得，对于高危急性白血病患者来说是一个可行的选择。
