School of Pharmacy, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Population Sciences, City of Hope, Duarte, California; Department of Hematology and HCT, City of Hope, Duarte, California.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Biol Blood Marrow Transplant. 2018 Sep;24(9):1802-1807. doi: 10.1016/j.bbmt.2018.04.006. Epub 2018 Apr 12.
We evaluated inosine monophosphate dehydrogenase (IMPDH) 1 and IMPDH2 pharmacogenetics in 247 recipient-donor pairs after nonmyeloablative hematopoietic cell transplant (HCT). Patients were conditioned with total body irradiation + fludarabine and received grafts from related or unrelated donors (10% HLA mismatch), with postgraft immunosuppression of mycophenolate mofetil (MMF) with a calcineurin inhibitor. Recipient and donor IMPDH genotypes (rs11706052, rs2278294, rs2278293) were not associated with day 28 T cell chimerism, acute graft-versus-host disease (GVHD), disease relapse, cytomegalovirus reactivation, nonrelapse mortality, or overall survival. Recipient IMPDH1 rs2278293 genotype was associated with a lower incidence of chronic GVHD (hazard ratio, .72; P = .008) in nonmyeloablative HCT recipients. Additional studies are needed to confirm these results with the goal of identifying predictive biomarkers to MMF that lower GVHD.
我们评估了非清髓性造血细胞移植（HCT）后 247 对供受者对中的肌苷单磷酸脱氢酶（IMPDH）1 和 IMPDH2 药物遗传学。患者接受全身照射+氟达拉滨预处理，并接受来自相关或不相关供者（10%HLA 错配）的移植物，移植后使用霉酚酸酯（MMF）和钙调神经磷酸酶抑制剂进行免疫抑制。受者和供者 IMPDH 基因型（rs11706052、rs2278294、rs2278293）与第 28 天 T 细胞嵌合、急性移植物抗宿主病（GVHD）、疾病复发、巨细胞病毒再激活、非复发死亡率或总生存率无关。非清髓性 HCT 受者中，IMPDH1 rs2278293 基因型与慢性 GVHD 的发生率较低相关（风险比，.72；P=.008）。需要进一步的研究来证实这些结果，以期确定降低 GVHD 的 MMF 预测生物标志物。
