Katsanis Emmanuel, Maher Keri, Roe Denise J, Simpson Richard J
Department of Pediatrics University of Arizona Tucson Arizona.
Department of Immunobiology University of Arizona Tucson Arizona.
EJHaem. 2020 May 26;1(1):286-292. doi: 10.1002/jha2.20. eCollection 2020 Jul.
We have initiated a single center phase I study in patients with hematologic malignancies progressively substituting day +4 posttransplant cyclophosphamide (PT-CY) with bendamustine (PT-BEN) following myeloablative conditioning (MAC) and T-cell replete haploidentical bone marrow transplantation (haplo-BMT). We report herein our interim analysis of our first three cohorts PT-CY (mg/kg)/PT-BEN (mg/m): 40/20, 20/60, and 0/90. All patients have tolerated PT-CY/BEN well with no dose limiting toxicities. Compared to contemporaneous controls undergoing haplo-BMT with the same MAC regimens but only PT-CY, we have observed earlier trilineage engraftment (.002 neutrophils, .014 platelets) and a lower incidence of cytomegalovirus reactivation (.016) in the PT-CY/BEN cohorts. After substituting day +4 PT-CY with PT-BEN, the registered trial (www.clinicaltrials.gov; NCT02996773) is proceeding to replace day +3 PT-CY with PT-BEN with a view to identifying further evidence on the potential advantages of PT-BEN.
我们开展了一项单中心I期研究，纳入血液系统恶性肿瘤患者，在清髓性预处理（MAC）和T细胞充足的单倍体相合骨髓移植（haplo - BMT）后，逐步用苯达莫司汀（PT - BEN）替代移植后第4天的环磷酰胺（PT - CY）。我们在此报告对前三个队列PT - CY（mg/kg）/PT - BEN（mg/m）：40/20、20/60和0/90的中期分析。所有患者对PT - CY/BEN耐受性良好，无剂量限制性毒性。与同期接受相同MAC方案但仅使用PT - CY的haplo - BMT对照患者相比，我们在PT - CY/BEN队列中观察到更早的三系造血重建（中性粒细胞P = 0.002，血小板P = 0.014）和更低的巨细胞病毒再激活发生率（P = 0.016）。在用PT - BEN替代移植后第4天的PT - CY后，注册试验（www.clinicaltrials.gov；NCT02996773）正在进行用PT - BEN替代移植后第3天的PT - CY，以进一步确定PT - BEN潜在优势的证据。
