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阿扎胞苷挽救疗法用于异基因造血干细胞移植后髓系恶性肿瘤复发的治疗

Azacitidine salvage therapy for relapse of myeloid malignancies following allogeneic hematopoietic SCT.

作者信息

Tessoulin B, Delaunay J, Chevallier P, Loirat M, Ayari S, Peterlin P, Le Gouill S, Gastinne T, Moreau P, Mohty M, Guillaume T

机构信息

1] Centre Hospitalier et Universitaire (CHU) de Nantes, Hématologie Clinique, Nantes, France [2] INSERM CRCNA, UMR 892, Nantes, France.

1] Centre Hospitalier et Universitaire (CHU) de Nantes, Hématologie Clinique, Nantes, France [2] INSERM CRCNA, UMR 892, Nantes, France [3] Centre d'Investigation Clinique en Cancérologie (CI2C), Nantes, France.

出版信息

Bone Marrow Transplant. 2014 Apr;49(4):567-71. doi: 10.1038/bmt.2013.233. Epub 2014 Feb 3.

Abstract

Patients with hematopoietic malignancies relapsing after allogeneic hematopoietic SCT (allo-HSCT) have a poor prognosis. We retrospectively analyzed the patients who received azacitidine in our center in the course of treatment of their post-transplant relapse. We identified 31 patients. Relapse occurred at a median of 3.7 (1.7-37.6) months following allo-HSCT. Patients received a median number of three cycles (1-12) of azacitidine (7 days, 75 mg/m(2) daily). Thirty-nine percent of patients had either a monosomal karyotype or a complex karyotype. Eleven patients (35%) received at least one DLI. Eleven patients responded to azacitidine, with four patients achieving a CR (13%). Median time to best response was 92 (35-247) days, with a median duration of 209 (64-751) days. One-year estimated survival rate was 14%. In conclusion, azacitidine may reinduce durable remissions in very few patients with AML or myelodysplastic syndrome. The toxicity related to azacitidine was high, although it may be difficult to distinguish between treatment-related side effects, namely due to cytopenia and toxicity due to the relapse or disease progression itself. Early administration of azacitidine after transplant followed by DLI should be considered as a pre-emptive therapy for potential relapse in patients with minimal residual disease or high-risk myeloid malignancies.

摘要

异基因造血干细胞移植(allo-HSCT)后复发的造血系统恶性肿瘤患者预后较差。我们回顾性分析了在本中心接受阿扎胞苷治疗移植后复发的患者。我们确定了31例患者。复发发生在allo-HSCT后的中位时间为3.7(1.7 - 37.6)个月。患者接受阿扎胞苷的中位周期数为3个周期(1 - 12个周期)(7天,每日75mg/m²)。39%的患者具有单体核型或复杂核型。11例患者(35%)接受了至少一次供者淋巴细胞输注(DLI)。11例患者对阿扎胞苷有反应,4例患者达到完全缓解(CR,13%)。达到最佳反应的中位时间为92(35 - 247)天,中位持续时间为209(64 - 751)天。1年估计生存率为14%。总之,阿扎胞苷可能仅在极少数急性髓系白血病(AML)或骨髓增生异常综合征患者中重新诱导持久缓解。与阿扎胞苷相关的毒性较高,尽管可能难以区分与治疗相关的副作用,即由于血细胞减少引起的副作用以及由于复发或疾病进展本身导致的毒性。移植后早期给予阿扎胞苷继以DLI应被视为对微小残留病患者或高危髓系恶性肿瘤患者潜在复发的抢先治疗。

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