Bruserud Øystein, Tsykunova Galina, Hernandez-Valladares Maria, Reikvam Hakon, Tvedt Tor Henrik Anderson
Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway.
Department of Medicine, Haukeland University Hospital, N-5021 Bergen, Norway.
Pharmaceuticals (Basel). 2021 May 2;14(5):423. doi: 10.3390/ph14050423.
Even though allogeneic stem cell transplantation is the most intensive treatment for acute myeloid leukemia (AML), chemo-resistant leukemia relapse is still one of the most common causes of death for these patients, as is transplant-related mortality, i.e., graft versus host disease, infections, and organ damage. These relapse patients are not always candidates for additional intensive therapy or re-transplantation, and many of them have decreased quality of life and shortened expected survival. The efficiency of azacitidine for treatment of posttransplant AML relapse has been documented in several clinical trials. Valproic acid is an antiepileptic fatty acid that exerts antileukemic activity through histone deacetylase inhibition. The combination of valproic acid and all-trans retinoic acid (ATRA) is well tolerated even by unfit or elderly AML patients, and low-toxicity chemotherapy (e.g., azacitidine) can be added to this combination. The triple combination of azacitidine, valproic acid, and ATRA may therefore represent a low-intensity and low-toxicity alternative for these patients. In the present review, we review and discuss the general experience with valproic acid/ATRA in AML therapy and we discuss its possible use in low-intensity/toxicity treatment of post-allotransplant AML relapse. Our discussion is further illustrated by four case reports where combined treatments with sequential azacitidine/hydroxyurea, valproic acid, and ATRA were used.
尽管异基因干细胞移植是急性髓系白血病（AML）最强化的治疗方法，但化疗耐药的白血病复发仍是这些患者最常见的死亡原因之一，移植相关死亡率也是如此，即移植物抗宿主病、感染和器官损伤。这些复发患者并不总是适合接受额外的强化治疗或再次移植，而且他们中的许多人生活质量下降，预期生存期缩短。阿扎胞苷治疗移植后AML复发的疗效已在多项临床试验中得到证实。丙戊酸是一种抗癫痫脂肪酸，通过抑制组蛋白脱乙酰酶发挥抗白血病活性。即使是身体状况不佳或老年AML患者，丙戊酸与全反式维甲酸（ATRA）的联合用药耐受性也良好，并且可以在此联合用药中加入低毒性化疗药物（如阿扎胞苷）。因此，阿扎胞苷、丙戊酸和ATRA的三联联合用药可能是这些患者的一种低强度、低毒性的替代治疗方案。在本综述中，我们回顾并讨论了丙戊酸/ATRA在AML治疗中的总体经验，并讨论了其在低强度/低毒性治疗异基因移植后AML复发中的可能应用。我们通过四个病例报告进一步阐述了我们的讨论，这些病例报告采用了阿扎胞苷/羟基脲、丙戊酸和ATRA序贯联合治疗。
