Department of Pediatrics, University of Arizona, Tucson, Arizona, USA.
The University of Arizona Cancer Center, Tucson, Arizona, USA.
Pediatr Blood Cancer. 2023 Feb;70(2):e30102. doi: 10.1002/pbc.30102. Epub 2022 Nov 17.
Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative option for patients with high-risk myeloid malignancies.
We present our 10-year experience (October 2012 to October 2021) of consecutive allo-HCT in patients with myeloid malignancies treated on the pediatric HCT service and conditioned with myeloablative targeted dose-busulfan (BU), fludarabine (FLU), and melphalan (MEL). Twenty-three children, adolescents, and young adult patients (CAYA) (median age 15.4 years) with acute myeloid leukemia (AML, n = 17), myelodysplastic syndrome (MDS, n = 4), or chronic myeloid leukemia (CML, n = 2) underwent allo-HCT post-BU-FLU-MEL. Four patients had treatment-related AML/MDS. Donor/stem cell source was matched sibling donor (MSD) PBSC (n = 7), matched unrelated donor (MUD) PBSC (n = 2), umbilical cord blood (UCB) (n = 3), or haploidentical-BMT (n = 11). Risk stratification was low (n = 2), intermediate (n = 15), high (n = 3), and very high risk (n = 1). The two patients with CML had failed tyrosine kinase inhibitor therapies.
With a median follow-up of 41.6 months, the relapse rate is only 4.5% with an overall survival (OS) 100%, progression-free survival (PFS) 95.5%, and graft-versus-host-free-relapse-free survival (GRFS) 67.8%. The donor source and the acute graft-versus-host disease (GvHD) prophylaxis regimen significantly impacted grade II-IV aGvHD 66.7% versus 19.2% (p = .039) and chronic graft-versus-host-disease (cGvHD) 66.7% versus 0% (p = .002) in the patients receiving MSD or MUD PBSC compared to haplo-BMT, respectively, resulting in improved GRFS in haplo-BMT, 83.3% compared to 40% matched donor peripheral blood stem cell transplant (PBSCT) (p = .025).
Our results demonstrate that BU-FLU-MEL is efficacious conditioning for disease control in young patients with myeloid malignancies undergoing MSD or alternative donor allo-HCT, but in the setting of PBSC grafts with cyclosporine A-methotrexate (CSA-MTX) GvHD prophylaxis, it results in an unacceptably high incidence of GvHD.
异基因造血细胞移植（allo-HCT）仍然是高危髓系恶性肿瘤患者的一种有治愈可能的治疗选择。
我们报告了我们在儿科 HCT 服务中治疗的患有髓系恶性肿瘤的患者在 10 年内（2012 年 10 月至 2021 年 10 月）连续接受 allo-HCT 的经验，这些患者接受了以靶向剂量白消安（BU）、氟达拉滨（FLU）和马法兰（MEL）为基础的清髓性预处理。23 例儿童、青少年和年轻成人患者（CAYA）（中位年龄 15.4 岁），其中急性髓系白血病（AML，n = 17）、骨髓增生异常综合征（MDS，n = 4）或慢性髓系白血病（CML，n = 2），在接受 BU-FLU-MEL 预处理后接受 allo-HCT。4 例患者患有治疗相关的 AML/MDS。供者/干细胞来源为匹配的同胞供者 PBSC（n = 7）、匹配的无关供者 PBSC（n = 2）、脐带血（UCB）（n = 3）或单倍体相合-BMT（n = 11）。危险分层为低危（n = 2）、中危（n = 15）、高危（n = 3）和极高危（n = 1）。2 例 CML 患者均已接受酪氨酸激酶抑制剂治疗失败。
中位随访 41.6 个月，复发率仅为 4.5%，总生存率（OS）为 100%，无进展生存率（PFS）为 95.5%，移植物抗宿主病-无复发存活率（GRFS）为 67.8%。供者来源和急性移植物抗宿主病（GvHD）预防方案显著影响 II-IV 级 aGvHD 的发生率，分别为 66.7%和 19.2%（p =.039），以及慢性 GvHD 的发生率，分别为 66.7%和 0%（p =.002），在接受 MSD 或 MUD PBSC 的患者中，与 haplo-BMT 相比，后者的 GRFS 得到改善，分别为 83.3%和 40%匹配供者外周血干细胞移植（PBSCT）（p =.025）。
我们的结果表明，BU-FLU-MEL 是年轻患者接受 MSD 或替代供者 allo-HCT 时控制疾病的有效预处理方案，但在 CSA-MTX 作为 GvHD 预防方案的 PBSC 移植物中，它会导致 GvHD 的发生率高得不可接受。
