Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA.
Universidade de Sao Paulo, Hospital das Clinicas, SP, Brazil.
Haematologica. 2019 Apr;104(4):835-843. doi: 10.3324/haematol.2018.202754. Epub 2018 Nov 15.
We determined the incidence of disability related to chronic graft--host disease (bronchiolitis obliterans, grade ≥2 keratoconjunctivitis sicca, sclerotic features or esophageal stricture) for three categories of alternative donor: cord blood, haplorelated marrow or peripheral blood with post-transplant cyclophosphamide, and unrelated single HLA-allele mismatched peripheral blood. Among 396 consecutive hematopoietic cell transplant recipients, 129 developed chronic graft--host disease with 3-year cumulative incidences of 8% for cord blood, 24% for haplorelated grafts, and 55% for unrelated single HLA-allele mismatched peripheral blood. Disability rates were significantly lower for cord blood [hazard ratio (HR) 0.13; 95% confidence interval (CI): 0.1-0.4] and for the haplorelated group (HR 0.31; 95% CI: 0.1-0.7) compared to the rate in the group transplanted with unrelated single HLA-allele mismatched peripheral blood. Cord blood recipients were also >2-fold more likely to return to work/school within 3 years from the onset of chronic graft--host disease (HR 2.54; 95% CI: 1.1-5.7, =0.02), and the haplorelated group trended similarly (HR 2.38; 95% CI: 1.0-5.9, =0.06). Cord blood recipients were more likely to discontinue immunosuppression than were recipients of unrelated single HLA-allele mismatched peripheral blood (HR 3.96; 95% CI: 1.9-8.4, =0.0003), similarly to the haplorelated group (HR 4.93; 95% CI: 2.2-11.1, =0.0001). Progression-free survival and non-relapse mortality did not differ between groups grafted from different types of donors. Our observations that, compared to recipients of unrelated single HLA-allele mismatched peripheral blood, recipients of cord blood and haplorelated grafts less often developed disability related to chronic graft--host disease, and were more likely to resume work/school, should help better counseling of pre-hematopoietic cell transplant candidates.
我们确定了三种供体来源(脐血、单倍体相关骨髓或外周血加移植后环磷酰胺、以及不相合单 HLA 等位基因错配外周血)的慢性移植物抗宿主病(细支气管炎闭塞性、≥2 级角结膜干燥症、硬化特征或食管狭窄)相关残疾的发生率。在 396 例连续造血细胞移植受者中,129 例发生慢性移植物抗宿主病,3 年累积发生率分别为脐血 8%、单倍体相关移植物 24%和不相合单 HLA 等位基因错配外周血 55%。与接受不相合单 HLA 等位基因错配外周血的患者相比,脐血(风险比[HR]0.13;95%置信区间[CI]:0.1-0.4)和单倍体相关组(HR 0.31;95%CI:0.1-0.7)的残疾率显著较低。与接受不相合单 HLA 等位基因错配外周血的患者相比,脐血受者在慢性移植物抗宿主病发病后 3 年内恢复工作/上学的可能性也高出 2 倍以上(HR 2.54;95%CI:1.1-5.7,=0.02),单倍体相关组也呈类似趋势(HR 2.38;95%CI:1.0-5.9,=0.06)。与接受不相合单 HLA 等位基因错配外周血的患者相比,脐血受者更有可能停止免疫抑制治疗(HR 3.96;95%CI:1.9-8.4,=0.0003),与单倍体相关组(HR 4.93;95%CI:2.2-11.1,=0.0001)相似。不同供体来源移植患者的无进展生存和非复发死亡率无差异。与接受不相合单 HLA 等位基因错配外周血的患者相比,我们观察到接受脐血和单倍体相关移植物的患者发生慢性移植物抗宿主病相关残疾的频率较低,更有可能恢复工作/上学,这有助于更好地为造血细胞移植前的候选者提供咨询。