Department of Pediatrics, University of Arizona, Tucson, Arizona; Department of Immunobiology, University of Arizona, Tucson, Arizona; Department of Medicine, University of Arizona, Tucson, Arizona; Department of Pathology, University of Arizona, Tucson, Arizona; University of Arizona Cancer Center, Tucson, Arizona; University of Arizona, Arizona and Banner University Medical Center, Tucson, Arizona.
Department of Pediatrics, University of Arizona, Tucson, Arizona; University of Arizona, Arizona and Banner University Medical Center, Tucson, Arizona.
Biol Blood Marrow Transplant. 2018 Oct;24(10):2034-2039. doi: 10.1016/j.bbmt.2018.06.007. Epub 2018 Jun 14.
More than half of patients undergoing hematopoietic cell transplantation at our institution are ethnic or racial minorities, making the search for matched unrelated donors more challenging. Since the introduction of haploidentical bone marrow transplant (haplo-BMT) into our pediatric BMT program in 2015, 69.2% of recipients have been minorities. Herein, we describe our experience with the first 13 pediatric and young adult patients with hematologic malignancies who have undergone T cell-replete haplo-BMT after myeloablative conditioning (MAC) at our institution. We have previously documented that in experimental haplo-BMT, post-transplant bendamustine (PT-BEN) is at least as effective as post-transplant cyclophosphamide (PT-CY) against graft-versus-host disease (GVHD) and elicits superior graft-versus-leukemia (GVL) effects. We report on, for the first time in humans, 4 patients treated with PT-CY and PT-BEN after haplo-BMT as part of our ongoing institutional phase I/II study (NCT02996773). The remaining 9 patients reviewed in this report received PT-CY. Our findings indicate that MAC haplo-BMT is well tolerated by children and young adults with advanced hematologic malignancies with no observed nonrelapse mortality or grades III to IV GVHD. All patients who underwent haplo-BMT remain alive and disease-free with a median follow-up of 15.6 months (range, 1.5 to 31.2). Preliminary findings from our ongoing clinical trial demonstrate that partial substitution of PT-BEN for PT-CY is feasible and safe after haplo-BMT as an immune modulatory strategy to alleviate GVHD and potentially more effectively preserve GVL.
我们机构进行造血细胞移植的患者中有一半以上是少数民族或少数族裔，这使得寻找匹配的无关供体更加具有挑战性。自 2015 年我们的儿科骨髓移植计划引入单倍体骨髓移植（haplo-BMT）以来，69.2%的受者为少数民族。在此，我们描述了我们在机构中接受清髓性预处理后接受 T 细胞富含的单倍体 BMT 的前 13 例血液系统恶性肿瘤的儿科和年轻成人患者的经验。我们之前已经证明，在实验性 haplo-BMT 中，移植后苯达莫司汀（PT-BEN）在预防移植物抗宿主病（GVHD）方面至少与移植后环磷酰胺（PT-CY）一样有效，并产生更好的移植物抗白血病（GVL）效果。我们首次报告了在我们正在进行的机构 I/II 期研究（NCT02996773）中，作为一部分接受 haplo-BMT 后接受 PT-CY 和 PT-BEN 治疗的 4 例患者。本报告中回顾的其余 9 例患者接受了 PT-CY。我们的发现表明，MAC haplo-BMT 可被患有晚期血液系统恶性肿瘤的儿童和年轻成人耐受，没有观察到非复发死亡率或 III 级至 IV 级 GVHD。所有接受 haplo-BMT 的患者均存活且无疾病，中位随访时间为 15.6 个月（范围，1.5 至 31.2）。我们正在进行的临床试验的初步结果表明，haplo-BMT 后用 PT-BEN 部分替代 PT-CY 作为免疫调节策略是可行且安全的，以减轻 GVHD 并可能更有效地保留 GVL。
