Hematology Clinic and Cellular Therapy, St. Antoine Hospital, Public Assistance Hospitals of Paris (AP-HP), Paris, France.
European Society of Blood and Marrow Transplantation Paris Office, St. Antoine Hospital, Paris, France.
Cancer. 2018 May 15;124(10):2142-2150. doi: 10.1002/cncr.31310. Epub 2018 Feb 22.
T-cell-depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high-risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full-matched donor.
To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T-cell-depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005-2011 [n = 191] and 2012-2015 [n = 117]).
The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft-versus-host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2-year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced-intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2-year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival. Similarly, leukemia-free survival and GvHD-free/relapse-free survival (GRFS) improved over time: the leukemia-free survival rate was 31% (25% vs 43% in the groups who underwent transplantation before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs 34%, respectively; P = .09). In addition, leukemia-free survival and GRFS improved among patients who received a RIC regimen.
The outcome of patients with acute leukemia who underwent T-cell-depleted haplo has improved over time. Cancer 2018;124:2142-50. © 2018 American Cancer Society.
在没有人类白细胞抗原（HLA）完全匹配供体的情况下，对于患有高危、急性白血病的患者，通常会提供 T 细胞耗竭、单倍体移植（haplo）。
为了确定移植时间的影响，作者将 2005 年至 2015 年间接受 T 细胞耗竭单倍体的 308 例新发急性白血病成人患者分为 2 组，根据他们接受移植的年份（2005-2011[ n = 191]和 2012-2015[ n = 117]）。
2012 年前接受移植的患者中位年龄为 41 岁，2012 年后接受移植的患者中位年龄为 46 岁（P =.04）。大多数患者患有急性髓细胞白血病（75%对 69%；P =.26），并且在移植时处于完全缓解 1 期（CR1）（55%对 64%；P =.12）。两组间 2 级、3 级和 4 级急性移植物抗宿主病（GvHD）和慢性 GvHD 的累积发生率无差异（急性 GvHD：20%对 2012 年前和后接受 haplo 的患者分别为 22%的累积发生率[P =.67]；慢性 GvHD：19%对 11%的累积发生率，分别；P =.12）。2 年复发率为 20%，非复发死亡率（NRM）率为 48%，且时间上无差异（21%对 19%，分别[P =.72]和 54%对 38%，分别为 2012 年前和后接受 haplo 的患者[P =.11]）。NRM 的主要原因是感染。2012 年后接受 haplo（危险比[HR]，0.57；P =.01）、年龄较小（HR，0.82；P =.02）和接受减强度调理（RIC）方案（HR，0.53；P =.01）与较低的 NRM 独立相关。2 年总生存率为 36%，2012 年后有所提高（2012 年前为 29%，后为 47%；P =.02）；并且对于处于 CR1 的患者，生存率更高（41%对 29%；P =.01）。多变量分析显示，2012 年后接受 haplo（HR，0.54；P =.003）和接受 RIC 方案（HR，0.54；P =.005）与总体生存率更好独立相关。同样，白血病无复发生存率和 GvHD 无复发/无复发生存率（GRFS）随时间改善：白血病无复发生存率为 31%（2012 年前和后接受移植的患者分别为 25%和 43%；P =.05），GRFS 率为 24%（19%和 34%，分别；P =.09）。此外，接受 RIC 方案的患者白血病无复发生存率和 GRFS 均有改善。
接受 T 细胞耗竭单倍体的急性白血病患者的预后随时间改善。癌症 2018；124：2142-50。2018 年美国癌症协会。
