Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Si Pu Lan Road, Yanjiao Development Zone, Langfang, China.
Ann Hematol. 2021 Jun;100(6):1579-1591. doi: 10.1007/s00277-020-04355-1. Epub 2020 Nov 24.
There are a limited number of studies comparing outcomes of busulfan (BU)-based myeloablative hematopoietic stem cell transplantation using unmanipulated haploidentical donors (HIDs), HLA-matched unrelated donors (MUDs), and HLA-matched sibling related donors (MSDs) in acute myeloid leukemia (AML) patients with complete remission (CR) status. With this background, we compared outcomes among 377 cases of CR following consecutive HID-HSCT for AML (CR) to 86 MUD and 92 MSD-HSCT cases. All patients received BU-based myeloablative conditioning and an unmanipulated graft within the same period. The median patient age was 23 years (range 1.1 to 65 years), and 230 patients (41.4%) were under age18. Among the 555 patients, 432 (77.8%) were of intermediate cytogenetic risk and 123 (22.2%) were of adverse risk. A total of 113 patients (20.5%) had FLT3-ITD+ AML, 425 patients (76.6%) were in first complete remission (CR1) post-transplant, and 130 (23.4%) patients were in second CR (CR2). GVHD prophylaxis included mycophenolate mofetil (MMF), cyclosporine-A (CSA) with short-term methotrexate (MTX) for HID, and MUD-HSCT. MMF is not used for MSD-HSCT. The median survival follow-up time was 42 months (range 18-91 months). The 3-year leukemia-free survival (LFS) among the HID, MUD, and MSD cohorts was 73.8% ± 4.8%, 66.4% ± 8.5%, 74.5% ± 2.4%, respectively (P = 0.637). Three-year overall survival (OS) was 74.9% ± 2.4%, 81.8% ± 4.3%, and 77.5% ± 4.5% among the HID, MUD, and MSD cohorts, respectively (P = 0.322). There were no difference among the relapse rate among the HID, MUD, and MSD donor cohorts (14.3% ± 4.0% vs 20.3% ± 6.4% vs 14.5% ± 2.2, respectively; P = 0.851) or the non-relapse mortality (NRM) (12.3% ± 3.5% vs 9.5% ± 3.2% vs 14.0% ± 1.8%, respectively; P = 0.441). Multivariate analyses showed that MRD-positive pre-HSCT was the only risk factor associated with a lower OS and LFS and higher risk of relapse among all 555 patients. Compared with the use of a MUD or MSD, an HID for HSCT had similar outcomes among AML patients with CR states who underwent an allo-HSCT with BU-based myeloablative conditioning. MFC-MRD-positive pre-HSCT was an independent negative factor impact on outcomes for AML patients in CR. We conclude that for AML patients who do not have a MSD or if an urgent transplant is required, HSCT from an HID is a valid option.
在完全缓解（CR）状态的急性髓系白血病（AML）患者中，使用未修饰的单倍体相合供体（HID）、HLA 匹配的无关供体（MUD）和 HLA 匹配的同胞相关供体（MSD）进行基于白消安（BU）的清髓性造血干细胞移植后，有数量有限的研究比较了结果。在此背景下，我们比较了连续 377 例接受基于 BU 的清髓性造血干细胞移植的 CR 后 AML（CR）患者（n=377）与 86 例 MUD 和 92 例 MSD 造血干细胞移植患者的结果。所有患者均在同一时期接受了基于 BU 的清髓性预处理和未修饰的移植物。中位患者年龄为 23 岁（范围 1.1 至 65 岁），230 例患者（41.4%）年龄<18 岁。在 555 例患者中，432 例（77.8%）为中危细胞遗传学风险，123 例（22.2%）为不良风险。共有 113 例（20.5%）患者为 FLT3-ITD+AML，425 例（76.6%）患者在移植后处于首次完全缓解（CR1），130 例（23.4%）患者处于第二次完全缓解（CR2）。GVHD 预防包括霉酚酸酯（MMF）、环孢素 A（CSA）联合短期甲氨蝶呤（MTX）用于 HID，以及 MUD 造血干细胞移植。MSD 造血干细胞移植不使用 MMF。中位随访时间为 42 个月（范围 18-91 个月）。HID、MUD 和 MSD 队列的 3 年无白血病生存率（LFS）分别为 73.8%±4.8%、66.4%±8.5%、74.5%±2.4%（P=0.637）。3 年总生存率（OS）分别为 74.9%±2.4%、81.8%±4.3%和 77.5%±4.5%（P=0.322）。HID、MUD 和 MSD 供体队列之间的复发率（14.3%±4.0%比 20.3%±6.4%比 14.5%±2.2%；P=0.851）或非复发死亡率（NRM）（12.3%±3.5%比 9.5%±3.2%比 14.0%±1.8%；P=0.441）无差异。多变量分析显示，HSCT 前 MRD 阳性是所有 555 例患者中唯一与 OS 和 LFS 较低、复发风险较高相关的危险因素。与使用 MUD 或 MSD 相比，在接受基于 BU 的清髓性预处理的allo-HSCT 后，AML 患者使用 HID 进行 HSCT 的结果相似。HSCT 前 MFC-MRD 阳性是影响 AML 患者 CR 预后的独立负性因素。我们得出结论，对于没有 MSD 的 AML 患者，或者如果需要紧急移植，HID 造血干细胞移植是一种有效的选择。
