Abstract:
Allogeneic hematopoietic cell transplantation (HCT) remains the sole curative treatment for most patients with hematologic malignancies. A well-matched donor (related or unrelated) remains 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 investigated outcomes of patients who underwent mismatched donor (related or unrelated) HCT with a radiation-based myeloablative conditioning MAC regimen in combination with fludarabine, and post-transplantation cyclophosphamide (PTCy) as higher-intensity graft-versus-host disease (GVHD) prophylaxis. We retrospectively assessed HCT outcomes in 155 patients who underwent mismatched donor HCT (related/haploidentical versus unrelated [MMUD]) with fractionated-total body irradiation (fTBI) plus fludarabine and PTCy as GVHD prophylaxis at City of Hope from 2015 to 2021. Diagnoses included acute lymphoblastic leukemia (46.5%), acute myelogenous leukemia (36.1%), and myelodysplastic syndrome (6.5%). The median age at HCT was 38 years, and 126 patients (81.3%) were an ethnic minority. The Hematopoietic Stem Cell Transplantation Comorbidity Index was ≥3 in 36.1% of the patients, and 29% had a Disease Risk Index (DRI) of high/very high. The donor type was haploidentical in 67.1% of cases and MMUD in 32.9%. At 2 years post-HCT, disease-free survival (DFS) was 75.4% and overall survival (OS) was 80.6% for all subjects. Donor type did not impact OS (hazard ratio [HR], .72; 95% confidence interval [CI], .35 to 1.49; P = .37) and DFS (HR, .78; 95% CI, .41 to 1.48; P = .44), but younger donors was associated with less grade III-IV acute GVHD (HR, 6.60; 95% CI, 1.80 to 24.19; P = .004) and less moderate or severe chronic GVHD (HR, 3.53; 95% CI, 1.70 to 7.34; P < .001), with a trend toward better survival (P = .099). The use of an MMUD was associated with significantly faster neutrophil recovery (median, 15 days versus 16 days; P = .014) and platelet recovery (median, 18 days versus 24 days; P = .029); however, there was no difference in GVHD outcomes between the haploidentical donor and MMUD groups. Nonrelapse mortality (HR, .86; 95% CI, .34 to 2.20; P = .76) and relapse risk (HR, .78; 95% CI, .33 to 1.85; P = .57) were comparable in the 2 groups. Patient age <40 years and low-intermediate DRI showed a DFS benefit (P = .004 and .029, respectively). High or very high DRI was the only predictor of increased relapse (HR, 2.89; 95% CI, 1.32 to 6.34; P = .008). In conclusion, fludarabine/fTBI with PTCy was well-tolerated in mismatched donor HCT, regardless of donor relationship to the patient, provided promising results, and increased access to HCT for patients without a matched donor, especially patients from ethnic minorities and patients of mixed race.
摘要:
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。