Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21287, USA.
Curr Opin Hematol. 2012 Nov;19(6):440-7. doi: 10.1097/MOH.0b013e32835822dc.
Once considered too dangerous for all but the sickest of patients, partially human leukocyte antigen (HLA)-mismatched, or HLA-haploidentical, related donor bone marrow transplantation (haploBMT) has seen a revival, thanks to the reduced intensity conditioning (RIC) regimens and graft-versus-host disease (GVHD) prophylaxis with high-dose posttransplantation cyclophosphamide (PT/Cy).
RIC haploBMT with high-dose PT/Cy is associated with a cumulative incidence of acute grades II-IV GVHD of approximately 30% and incidences of chronic GVHD and nonrelapse mortality (NRM) less than 15%. These results have been confirmed in single and multicenter clinical trials. PT/Cy appears to nullify the detrimental effects of HLA mismatching on the outcome of haploBMT, thereby permitting the selection of haplo donors based upon criteria other than HLA matching. Overall and event-free survivals of RIC haploBMT compare favorably to the outcomes of RIC unrelated adult donor or umbilical cord blood stem cell transplantation.
With its improved toxicity profile, haploBMT is a feasible alternative for patients who lack an HLA-matched donor and can now be applied to treat patients with nonmalignant disorders.
部分人白细胞抗原(HLA)不匹配或 HLA 单倍体相合相关供者骨髓移植(haploBMT)曾被认为对除最病重患者之外的所有患者都太危险,但由于采用了强度降低的预处理(RIC)方案和高剂量移植后环磷酰胺(PT/Cy)预防移植物抗宿主病(GVHD),haploBMT 得以复兴。
RIC haploBMT 联合高剂量 PT/Cy 导致急性 II-IV 级 GVHD 的累积发生率约为 30%,慢性 GVHD 和非复发死亡率(NRM)低于 15%。这些结果在单中心和多中心临床试验中得到了证实。PT/Cy 似乎消除了 HLA 不匹配对 haploBMT 结果的不利影响,从而可以根据 HLA 匹配以外的标准选择 haplo 供者。RIC haploBMT 的总体生存率和无事件生存率与 RIC 无关供者或脐带血干细胞移植的结果相当。
haploBMT 的毒性谱得到改善,为缺乏 HLA 匹配供者的患者提供了一种可行的选择,现在可用于治疗非恶性疾病患者。