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异基因造血干细胞移植联合大剂量 post-transplantation cyclophosphamide 治疗年龄≥55 岁的急性淋巴细胞白血病患者。

Allogeneic Blood or Marrow Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Acute Lymphoblastic Leukemia in Patients Age ≥55 Years.

机构信息

National Heart Lung and Blood Institute, University School of Medicine, Baltimore, Maryland.

National Heart Lung and Blood Institute, University School of Medicine, Baltimore, Maryland.

出版信息

Transplant Cell Ther. 2023 Mar;29(3):182.e1-182.e8. doi: 10.1016/j.jtct.2022.12.018. Epub 2022 Dec 29.

Abstract

Patients age ≥55 years with acute lymphoblastic leukemia (ALL) fare poorly with conventional chemotherapy, with a 5-year overall survival (OS) of ∼20%. Tyrosine kinase inhibitors and novel B cell-targeted therapies can improve outcomes, but rates of relapse and death in remission remain high. Allogeneic blood or marrow transplantation (alloBMT) provides an alternative consolidation strategy, and post-transplantation cyclophosphamide (PTCy) facilitates HLA-mismatched transplantations with low rates of nonrelapse mortality (NRM) and graft-versus-host disease (GVHD). The transplantation database at Johns Hopkins was queried for patients age ≥55 years who underwent alloBMT for ALL using PTCy. The database included 77 such patients. Most received reduced-intensity conditioning (RIC) (88.3%), were in first complete remission (CR1) (85.7%), and had B-lineage disease (90.9%). For the entire cohort, 5-year relapse-free survival (RFS) and overall survival (OS) were 46% (95% confidence interval [CI], 34% to 57%) and 49% (95% CI, 37% to 60%), respectively. Grade III-IV acute GVHD occurred in only 3% of patients, and chronic GVHD occurred in 13%. In multivariable analysis, myeloablative conditioning led to worse RFS (hazard ratio [HR], 4.65; P = .001), whereas transplantation in CR1 (HR, .30; P = .004) and transplantation for Philadelphia chromosome-positive (Ph) ALL versus T-ALL (HR, .29; P = .03) were associated with improved RFS. Of the 54 patients who underwent RIC alloBMT in CR1 for B-ALL, the 5-year RFS and OS were 62% (95% CI, 47% to 74%) and 65% (95% CI, 51% to 77%), respectively, with a 5-year relapse incidence of 16% (95% CI, 7% to 27%) and an NRM of 24% (95% CI, 13% to 36%). RIC alloBMT with PTCy in CR1 represents a promising consolidation strategy for B-ALL patients age ≥55 years.

摘要

患者年龄≥55 岁的急性淋巴细胞白血病(ALL)患者对常规化疗的反应较差,5 年总生存率(OS)约为 20%。酪氨酸激酶抑制剂和新型 B 细胞靶向治疗可以改善预后,但缓解后的复发率和死亡率仍然很高。异基因血液或骨髓移植(alloBMT)提供了一种替代巩固策略,移植后环磷酰胺(PTCy)可以促进 HLA 不匹配移植,非复发死亡率(NRM)和移植物抗宿主病(GVHD)的发生率低。约翰霍普金斯大学的移植数据库对接受 PTCy 治疗 ALL 的年龄≥55 岁的 alloBMT 患者进行了查询。该数据库包括 77 名此类患者。大多数患者接受了低强度预处理(RIC)(88.3%),处于首次完全缓解(CR1)(85.7%),并患有 B 细胞系疾病(90.9%)。对于整个队列,5 年无复发生存率(RFS)和总生存率(OS)分别为 46%(95%CI,34%至 57%)和 49%(95%CI,37%至 60%)。仅 3%的患者发生 III-IV 级急性 GVHD,13%的患者发生慢性 GVHD。多变量分析显示,清髓性预处理导致 RFS 较差(危险比[HR],4.65;P=0.001),而 CR1 中的移植(HR,0.30;P=0.004)和费城染色体阳性(Ph)ALL 与 T-ALL 相比的移植(HR,0.29;P=0.03)与 RFS 改善相关。在 54 名在 CR1 中接受 B-ALL 的 RIC alloBMT 的患者中,5 年 RFS 和 OS 分别为 62%(95%CI,47%至 74%)和 65%(95%CI,51%至 77%),5 年复发率为 16%(95%CI,7%至 27%),NRM 为 24%(95%CI,13%至 36%)。CR1 中接受 PTCy 的 RIC alloBMT 是≥55 岁 B-ALL 患者有希望的巩固策略。

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