Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Freiburg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Hematology-Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Semin Cancer Biol. 2018 Aug;51:68-79. doi: 10.1016/j.semcancer.2017.10.011. Epub 2017 Nov 9.
Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine. However, hypomethylating therapy does not eradicate the malignant clone in MDS or JMML and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option. An emerging concept with intriguing potential is the combination of hypomethylating therapy and HSCT. Possible advantages include disease control with good tolerability during donor search and HSCT preparation, improved antitumoral alloimmunity, and reduced risk of relapse even with non-myeloablative regimens. Herein we review the current role of pre- and post-transplant therapy with hypomethylating agents in MDS and JMML.
骨髓增生异常综合征（MDS）是一种克隆性骨髓疾病，通常发生于老年人，其特征为无效造血、外周血细胞减少以及向急性髓系白血病进展的风险。幼年型粒单核细胞白血病（JMML）是一种发生于幼儿的侵袭性骨髓增殖性肿瘤。这些恶性髓系疾病的共同点是常规化疗获益有限，对 DNA 去甲基化剂 5-氮杂胞苷（阿扎胞苷）或地西他滨的表观遗传学治疗特别敏感。然而，去甲基化治疗并不能消除 MDS 或 JMML 中的恶性克隆，异基因造血干细胞移植（HSCT）仍然是唯一的治愈性治疗选择。一个具有诱人潜力的新兴概念是将去甲基化治疗与 HSCT 相结合。可能的优势包括在供者寻找和 HSCT 准备期间具有良好耐受性的疾病控制、改善抗肿瘤同种异体免疫以及即使采用非清髓性方案也降低复发风险。本文综述了 MDS 和 JMML 中移植前和移植后应用去甲基化剂治疗的现状。
