Karakulska-Prystupiuk E, Drozd-Sokołowska J, Waszczuk-Gajda A, Stefaniak A, Dwilewicz-Trojaczek J, Kulikowska A, Chmarzyńska-Mróz E, Basak G, Paluszewska M, Boguradzki P, Jędrzejczak W
Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
Transplant Proc. 2018 Sep;50(7):2212-2217. doi: 10.1016/j.transproceed.2018.02.148. Epub 2018 Mar 14.
Relapse is the leading cause of treatment failure for myeloid malignancies treated with allogeneic hematopoietic stem cell transplantation. Treatment options are very limited and use of azacitidine is one of the available options.
This was a retrospective, single-institution study. Of 28 evaluated patients, 18 were males, and the median age was 60 years (range, 15-78). There were 15 patients with acute myeloid leukemia, 8 with myelodysplastic syndrome, 4 with chronic myelomonocytic leukemia, and 1 with primary myelofibrosis. Ten patients received azacitidine for overt relapse, 14 received it as a preemptive therapy, and 4 others received it as maintenance treatment after allo-hematopoietic cell transplant (HSCT). Eleven patients received a donor lymphocyte infusion (DLI).
The patients received median 5 (1-9) cycles of azacitidine in preemptive and maintenance therapy and median 2.5 (1-9) cycles in patients with relapse. Thirty-nine percent of patients received DLIs. Median overall survival was 6.1 months (95% CI, 0.7-13) for relapse therapy vs 21.2 months (95% CI, 8.4-inf) for preemptive therapy. Among patients treated for relapse, 30% achieved temporary disease control and underwent the second allo-HSCT. A complete, cytogenetic remission was achieved in 50% of patients and stable minimal residual disease in 14% of patients in a group with preemptive therapy. Toxicity was considerable; neutropenia (71%), anemia (14%), thrombocytopenia (36%), and serious infections (36%) were observed in the preemptive setting.
These data support the notion that azacitidine is best used as a preemptive therapy against relapse for patients after allo-HSCT performed for myeloid malignancy. Applying azacitidine as therapy for ongoing relapse after allo-HSCT may lead to stable disease and allow for better performance of the second allo-HSCT.
复发是异基因造血干细胞移植治疗髓系恶性肿瘤治疗失败的主要原因。治疗选择非常有限，使用阿扎胞苷是可用的选择之一。
这是一项回顾性单机构研究。在28例接受评估的患者中，18例为男性，中位年龄为60岁（范围15 - 78岁）。其中15例为急性髓系白血病患者，8例为骨髓增生异常综合征患者，4例为慢性粒单核细胞白血病患者，1例为原发性骨髓纤维化患者。10例患者因明显复发接受阿扎胞苷治疗，14例作为抢先治疗接受阿扎胞苷治疗，另外4例在异基因造血细胞移植（HSCT）后作为维持治疗接受阿扎胞苷治疗。11例患者接受了供体淋巴细胞输注（DLI）。
在抢先治疗和维持治疗中，患者接受阿扎胞苷的中位疗程为5（1 - 9）个周期，复发患者接受阿扎胞苷的中位疗程为2.5（1 - 9）个周期。39%的患者接受了DLI。复发治疗的中位总生存期为6.1个月（95%CI，0.7 - 13），而抢先治疗为21.2个月（95%CI，8.4 - 无穷大）。在接受复发治疗的患者中，30%实现了疾病的临时控制并接受了第二次异基因HSCT。在抢先治疗组中，50%的患者实现了完全细胞遗传学缓解，14%的患者实现了稳定的微小残留病。毒性相当大；在抢先治疗中观察到中性粒细胞减少（71%）、贫血（14%）、血小板减少（36%）和严重感染（36%）。
这些数据支持这样一种观点，即阿扎胞苷最好用作异基因HSCT治疗髓系恶性肿瘤后患者预防复发的抢先治疗。将阿扎胞苷用作异基因HSCT后持续复发的治疗可能会导致疾病稳定，并使第二次异基因HSCT的效果更好。
