背景:异基因造血细胞移植(HCT)仍然是大多数血液系统恶性肿瘤患者唯一的治愈性治疗方法。匹配良好的供体(相关或无关)仍然是接受同种异体HCT的患者的首选供体;然而,大量患者依赖配对相关(单倍体相合)或无关供体的替代供体选择来获得HCT.在这项回顾性研究中,我们描述了接受不匹配供体(相关或无关)HCT与基于辐射的MAC方案联合FLU的患者的结局,和PTCy作为更高强度的GVHD预防。我们根据供体类型分析了结果。
方法:我们回顾性评估了155例患者的HCT结果,这些患者接受了不匹配的供体HCT[相关/单倍体与无关(MMUD)],并进行了分次全身照射(FTBI)加氟达拉滨和移植后环磷酰胺(PTCy)作为移植物抗宿主病(GVHD)的预防。诊断包括所有(46.5%),AML(36.1%)和MDS(6.5%)。HCT的中位年龄为38岁,126名(81.3%)患者来自少数民族。36.1%的HCT-CI≥3,29%的患者疾病风险指数(DRI)高/非常高。供体类型为haplo(67.1%)或MMUD(32.9%)。
结果:在HCT后2年,所有受试者的无病生存率(DFS)和总生存率(OS)分别为75.4%和80.6%,分别。捐赠者类型不影响OS[HR=0.72,(95%CI:0.35,1.49),p=0.37]和DFS[HR=0.78,(95%CI:0.41,1.48),p=0.44]但较年轻的供体导致III-IV级急性GVHD较少(aGVHD,[HR=6.60,(95%CI:1.80,24.19),p=0.004]和较少的中度或重度慢性GVHD[HR=3.53,(95%CI:1.70,7.34),p<0.001],有更好的生存率(p=0.099)。MMUD导致中性粒细胞明显加快(中位数15天vs16天,p=0.014)和血小板恢复(中位数18vs24天,p=0.029);然而,这些组间GVHD结局无差异.非复发死亡率[HR=0.86,(95%CI:0.34,2.20),p=0.76]和复发风险[HR=0.78,95CI:(0.33,1.85),p=0.57]在两组之间具有可比性。患者年龄<40岁和低中间DRI显示DFS益处(分别为p=0.004和0.029)。高或非常高的DRI是复发增加的唯一预测因子[HR=2.89,95CI:(1.32,6.34),p=0.008]。
结论:结论:与PTCy的FLU/FTBI在错配供体HCT中耐受性良好,不管与病人的关系,提供了有希望的结果,并改善了没有匹配供体的患者,尤其是来自少数民族和混合种族的患者获得HCT的机会。
BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) remains the only curative treatment for most patients with hematological malignancies. A well-matched donor (related or unrelated) remains as the preferred donor for patients undergoing allogeneic HCT; however, a large number of patients rely on alternative donor choices of mismatched related (haploidentical) or unrelated donors to access HCT. In this retrospective study, we described outcomes of patients who underwent mismatched donor (related or unrelated) HCT with radiation-based MAC regimen in combination with FLU, and PTCy as higher intensity GVHD prophylaxis. We analyzed outcomes based on donor type.
METHODS: We retrospectively assessed HCT outcomes in 155 patients who underwent mismatched donor HCT [related/haploidentical vs unrelated (MMUD)] with fractionated-total body irradiation (FTBI) plus fludarabine and post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis at City of Hope from 2015 to 2021. Diagnoses included ALL (46.5%), AML (36.1%) and MDS (6.5%). The median age at HCT was 38 years and 126 (81.3%) patients were from ethnic minorities. HCT-CI was ≥3 in 36.1% and 29% had a disease-risk-index (DRI) of high/very high. Donor type was haplo (67.1%) or MMUD (32.9%).
RESULTS: At 2-years post-HCT, disease-free survival (DFS) and overall survival (OS) for all subjects were 75.4% and 80.6%, respectively. Donor type did not impact OS [HR=0.72, (95% CI: 0.35,1.49), p=0.37] and DFS [HR=0.78, (95% CI: 0.41,1.48), p=0.44] but younger donors resulted in less grade III-IV acute GVHD (aGVHD, [HR=6.60, (95% CI: 1.80,24.19), p=0.004] and less moderate or severe chronic GVHD [HR=3.53, (95% CI: 1.70,7.34), p<0.001] with a trend toward better survival (p=0.099). MMUD led to significantly faster neutrophil (median 15 vs 16 days, p=0.014) and platelet recovery (median 18 vs 24 days, p=0.029); however, there was no difference in GVHD outcomes between these groups. Non-relapse mortality [HR=0.86, (95% CI: 0.34,2.20), p=0.76] and relapse risk [HR=0.78, 95%CI: (0.33,1.85), p=0.57] were comparable between the two groups. Patient age <40-years and low-intermediate DRI showed a DFS benefit (p=0.004 and 0.029, respectively). High or very High DRI was the only predictor of increased relapse [HR=2.89, 95%CI: (1.32, 6.34), p=0.008].
CONCLUSIONS: In conclusion, FLU/FTBI with PTCy was well-tolerated in mismatched donor HCT, regardless of relationship with patient, provided promising results, and improved access to HCT for patients without a matched donor especially patients from ethnic minorities and mixed race.