Background: The impact of donor graft cell composition on post-HCT outcomes in AML remains controversial. Furthermore, it is unknown whether this interacts with pre-HCT MRD status. We evaluated the impact of CD34+ and CD3+ cell doses on outcomes of myeloablative conditioning (MAC) HCT in patients with myelodysplastic neoplasm (MDS)/AML or AML with and without detectable MRD in pre-HCT bone marrow specimens.Methods: We utilized an electronic database to identify all adults ≥18 years with MDS/AML or AML who underwent MAC and received 10/10 HLA-matched sibling or unrelated donor mobilized PBSC allografts in first morphologic remission between 2006 and 2023 at the University of Washington/Fred Hutchinson Cancer Center.Results: Among 385 adults, we found a progressive decrease in relapse incidence and improved survival with increasing CD34+ doses up to a threshold of 5.61 × 106/kg, above which the relapse risk no longer decreased. After multivariable adjustment, a low CD34+ dose was associated with increased risk of relapse as well as lower overall and relapse-free survival. Similar results were obtained for patients with and without pre-HCT MRD. Higher CD3+ doses were linearly associated with an increased incidence of moderate–severe chronic GVHD.Conclusions: Our data identify a non-linear relationship between CD34+ cell dose and relapse risk in AML patients undergoing myeloablative allogeneic HCT, with no apparent added benefit beyond a CD34+ dose threshold. Our findings suggest that donor graft composition impacts outcomes in adults with AML undergoing allogeneic HCT after MAC, independent of pre-HCT MRD status; however, additional studies are needed for other donor cell scenarios.
背景:供体移植物细胞组成对急性髓系白血病(AML)患者造血细胞移植(HCT)后预后的影响仍存在争议。此外,其是否与移植前微小残留病(MRD)状态存在交互作用尚不明确。本研究评估了CD34+和CD3+细胞剂量对骨髓增生异常肿瘤(MDS)/AML或AML患者在接受清髓性预处理(MAC)后HCT预后的影响,并分析了移植前骨髓标本中是否检出MRD的差异。 方法:我们利用电子数据库,筛选了2006年至2023年间在华盛顿大学/弗雷德·哈钦森癌症中心接受MAC、首次达到形态学缓解并接受10/10 HLA匹配同胞或无关供体动员外周血干细胞(PBSC)异基因移植的所有18岁及以上MDS/AML或AML成年患者。 结果:在385例成年患者中,我们发现随着CD34+细胞剂量增加至5.61 × 10^6/kg阈值,复发率逐渐降低,生存率改善;超过该阈值后,复发风险不再进一步下降。经多变量调整后,低CD34+细胞剂量与复发风险增加、总生存率和无复发生存率降低相关。无论移植前MRD状态如何,患者均呈现相似结果。较高CD3+细胞剂量与中重度慢性移植物抗宿主病(GVHD)发生率呈线性正相关。 结论:我们的数据揭示了接受清髓性异基因HCT的AML患者中,CD34+细胞剂量与复发风险之间存在非线性关系,超过特定剂量阈值后无明显额外获益。研究结果表明,供体移植物细胞组成影响接受MAC后异基因HCT的AML成年患者的预后,且该影响独立于移植前MRD状态;然而,针对其他供体细胞类型的情况仍需进一步研究。