Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Duke University, Durham, North Carolina.
Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University, Durham, North Carolina.
Biol Blood Marrow Transplant. 2017 Nov;23(11):1949-1954. doi: 10.1016/j.bbmt.2017.06.027. Epub 2017 Jul 17.
Treatment-related mortality (TRM) remains elevated in adult patients undergoing umbilical cord blood transplantation (UCBT), including an early rise in TRM suggestive of excessive toxicity associated with the standard myeloablative total body irradiation (TBI), fludarabine, and cyclophosphamide regimen. In an attempt to reduce regimen-related toxicity, we previously studied a modified myeloablative regimen with TBI (1350 cGy) and fludarabine (160 mg/m); TRM was decreased, but neutrophil engraftment was suboptimal. Therefore, to improve engraftment while still minimizing regimen-related toxicity, we piloted a myeloablative regimen with the addition of thiotepa (10 mg/kg) to TBI and fludarabine conditioning. Thirty-one adult patients (median age, 46 years; range, 19 to 65) with hematologic malignancies (acute leukemia/myelodysplastic syndrome, 77%; lymphoid malignancy, 23%) underwent single (n = 1) or double (n = 30) UCBT from 2010 to 2015 at our institution. The cumulative incidence of neutrophil engraftment was 90% (95% confidence interval [CI], 70% to 97%) by 60 days, with a median time to engraftment of 21 days (95% CI, 19 to 26). The cumulative incidence of platelet engraftment was 77% (95% CI, 57% to 89%) by 100 days, with a median time to engraftment of 47 days (95% CI, 37 to 73). Cumulative incidences of grades II to IV and grades III to IV acute graft-versus-host disease (GVHD) at day 100 were 45% (95% CI, 27% to 62%) and 10% (95% CI, 2% to 23%), respectively. The overall incidence of chronic GVHD at 2 years was 40% (95% CI, 22% to 57%), with 17% of patients (95% CI, 6% to 33%) experiencing moderate to severe chronic GVHD by 2 years. TRM at 180 days was 13% (95% CI, 4% to 27%), at 1 year 24% (95% CI, 10% to 41%), and at 3 years 30% (95% CI, 13% to 49%). Relapse at 1 year was 13% (95% CI, 4% to 27%) and at 3 years 19% (95% CI, 6% to 38%). With a median follow-up of 35.5 months (95% CI, 12.7 to 52.2), disease-free and overall survival at 3 years were 51% (95% CI, 29% to 69%) and 57% (95% CI, 36% to 73%), respectively. This regimen represents a reasonable alternative to myeloablative conditioning with TBI, fludarabine, and cyclophosphamide and warrants further study.
治疗相关死亡率（TRM）在接受脐带血移植（UCBT）的成年患者中仍然居高不下，包括早期 TRM 升高提示与标准全身照射（TBI）、氟达拉滨和环磷酰胺方案相关的毒性过高。为了降低方案相关毒性，我们之前研究了一种改良的骨髓清除性方案，其中包括 TBI（1350 cGy）和氟达拉滨（160mg/m）；TRM 降低，但中性粒细胞植入不理想。因此，为了在仍最大限度降低方案相关毒性的情况下改善植入，我们试用了一种骨髓清除性方案，在 TBI 和氟达拉滨预处理中加入噻替哌（10mg/kg）。2010 年至 2015 年，我们机构的 31 名患有血液系统恶性肿瘤（急性白血病/骨髓增生异常综合征，77%；淋巴恶性肿瘤，23%）的成年患者（中位年龄，46 岁；范围，19 至 65 岁）接受了单次（n=1）或双次（n=30）UCBT。中性粒细胞植入的累积发生率为 90%（95%置信区间[CI]，70%至 97%），60 天内达到，中位植入时间为 21 天（95%CI，19 至 26）。血小板植入的累积发生率为 77%（95%CI，57%至 89%），100 天达到，中位植入时间为 47 天（95%CI，37 至 73）。第 100 天 II 至 IV 级和 III 至 IV 级急性移植物抗宿主病（GVHD）的累积发生率分别为 45%（95%CI，27%至 62%）和 10%（95%CI，2%至 23%）。2 年慢性 GVHD 的总发生率为 40%（95%CI，22%至 57%），17%的患者（95%CI，6%至 33%）在 2 年内出现中度至重度慢性 GVHD。180 天的 TRM 为 13%（95%CI，4%至 27%），1 年为 24%（95%CI，10%至 41%），3 年为 30%（95%CI，13%至 49%）。1 年时的复发率为 13%（95%CI，4%至 27%），3 年时为 19%（95%CI，6%至 38%）。中位随访 35.5 个月（95%CI，12.7 至 52.2），3 年时无病生存率和总生存率分别为 51%（95%CI，29%至 69%）和 57%（95%CI，36%至 73%）。与 TBI、氟达拉滨和环磷酰胺的骨髓清除性方案相比，该方案是一种合理的替代方案，值得进一步研究。
