Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC 27705, USA.
Biol Blood Marrow Transplant. 2011 Jun;17(6):867-74. doi: 10.1016/j.bbmt.2010.09.009. Epub 2010 Sep 22.
High treatment-related mortality (TRM) and high graft failure rate are serious concerns in HLA-mismatched umbilical cord blood (UCB) transplantation with myeloablative conditioning. We conducted a prospective trial of dual UCB transplantation using modified myeloablation consisting of total-body irradiation (TBI; 1350 cGy) and fludarabine (Flu) (160 mg/m(2)). Twenty-seven patients (median age, 33 years; range: 20-58 years) with hematologic malignancies were enrolled. The median combined cryopreserved total nucleated cell (TNC) dose was 4.3 × 10(7)/kg (range: 3.2-7.7 × 10(7)/kg). The cumulative incidences of neutrophil (≥500/μL) and platelet (≥50,000/μL) engraftment were 80% (95% confidence interval [CI], 58%-91%) and 68% (95% CI, 46%-83%), respectively. Among engrafted patients, a single cord blood unit was predominant by 100 days posttransplantation. A higher cryopreserved and infused TNC dose and infused CD3(+) cell dose were significant factors associated with the predominant UCB unit (P = .032, .020, and .042, respectively). TRM and relapse rates at 2 years were 28% (95% CI, 12%-47%) and 20% (95% CI, 7%-37%), respectively. Cumulative incidences of grades II-IV and grades III-IV acute graft-versus-host disease (aGVHD) were 37% (95% CI, 20%-55%) and 11% (95% CI, 3%-26%), respectively, and that of chronic GVHD was 31% (95% CI, 15%-49%). With a median follow-up of 23 months, overall survival and disease-free survival rates at 2 years were 58% (95% CI, 34%-75%) and 52% (95% CI, 29%-70%), respectively. This study supports the use of TBI 1350 cGy/Flu as an alternative to conventional myeloablative conditioning for dual UCB transplantation.
高治疗相关死亡率（TRM）和高移植物失败率是 HLA 不相合脐带血（UCB）移植中使用清髓性预处理的严重问题。我们进行了一项前瞻性研究，采用改良的清髓性预处理，包括全身照射（TBI；1350 cGy）和氟达拉滨（Flu）（160 mg/m2）进行双 UCB 移植。共纳入 27 例血液系统恶性肿瘤患者（中位年龄 33 岁；范围：20-58 岁）。中位联合冷冻保存的总核细胞（TNC）剂量为 4.3×10(7)/kg（范围：3.2-7.7×10(7)/kg）。中性粒细胞（≥500/μL）和血小板（≥50,000/μL）植入的累积发生率分别为 80%（95%置信区间 [CI]，58%-91%）和 68%（95% CI，46%-83%）。在植入的患者中，100 天移植后以单个脐带血单位为主。冷冻保存和输注的 TNC 剂量以及输注的 CD3(+)细胞剂量较高是与主要 UCB 单位相关的显著因素（P=.032，.020 和.042）。2 年时 TRM 和复发率分别为 28%（95% CI，12%-47%）和 20%（95% CI，7%-37%）。2 级-4 级和 3 级-4 级急性移植物抗宿主病（aGVHD）的累积发生率分别为 37%（95% CI，20%-55%）和 11%（95% CI，3%-26%），慢性 GVHD 的累积发生率为 31%（95% CI，15%-49%）。中位随访 23 个月时，2 年时的总生存率和无病生存率分别为 58%（95% CI，34%-75%）和 52%（95% CI，29%-70%）。这项研究支持使用 1350 cGy/TBI 和 Flu 作为传统清髓性预处理的替代方法，用于双 UCB 移植。
