Holle N, de Witte T, Mandigers C, Schaap N, Raymakers R
Department of Hematology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
Neth J Med. 2010 Aug;68(1):293-8.
Primary myelofibrosis is a clonal haematopoietic stem cell disease, characterised by marrow stromal fibrosis, extramedullary haematopoiesis, splenomegaly, hepatomegaly and progressive cytopenia. Therapeutic options once cytopenia has developed are limited to supportive care, such as erythrocyte transfusions and growth factors. The aetiology has become more clear, especially since JAK-2 mutations were found, resulting in increased production of cytokines. The immune-modulating drug thalidomide and its derivative lenalidomide have shown to be effective in reducing cytopenia, most probably by inhibiting the cytokine responses. In some patients the bone marrow fibrosis disappears. We describe the experience with these drugs in a cohort of 14 patients for thalidomide and seven for lenalidomide (in six patients lenalidomide was given after thalidomide and one patient received lenalidomide upfront). Thalidomide gave clinical improvement in 6/14 patients, but its use was limited mainly due to toxicity, especially the development of neuropathy. The drug could be given for a median period of 15.5 months in responding patients. Lenalidomide was effective in 4/7 of the patients, in some patients with no response on thalidomide. Due to the more favourable toxicity profile, the median duration of therapy was 19 months, with 3/4 patients on therapy longer than 19 months. These data are discussed in view of the clinical studies published. We conclude that lenalidomide is preferred in myelofibrosis, given a higher response rate and more favourable toxicity profile. If no response the addition of prednisone can be considered. In some patients it can normalise haemoglobin and make them transfusion independent.
原发性骨髓纤维化是一种克隆性造血干细胞疾病，其特征为骨髓基质纤维化、髓外造血、脾肿大、肝肿大和进行性血细胞减少。一旦出现血细胞减少，治疗选择仅限于支持性治疗，如红细胞输注和生长因子。病因已变得更加明确，尤其是自发现JAK-2突变以来，导致细胞因子产生增加。免疫调节药物沙利度胺及其衍生物来那度胺已显示出可有效减少血细胞减少，很可能是通过抑制细胞因子反应实现的。在一些患者中，骨髓纤维化消失。我们描述了在一组14例使用沙利度胺和7例使用来那度胺的患者中的用药经验（6例患者在使用沙利度胺后使用来那度胺，1例患者直接使用来那度胺）。沙利度胺使6/14例患者临床症状改善，但其使用主要因毒性受限，尤其是神经病变的发生。在有反应的患者中，该药物的中位使用时间为15.5个月。来那度胺在4/7例患者中有效，其中一些患者对沙利度胺无反应。由于毒性特征更有利，治疗的中位持续时间为19个月，3/4的患者治疗时间超过19个月。结合已发表的临床研究对这些数据进行了讨论。我们得出结论，鉴于来那度胺有更高的反应率和更有利的毒性特征，在骨髓纤维化中更倾向使用来那度胺。如果无反应，可考虑加用泼尼松。在一些患者中，它可使血红蛋白正常化并使其无需输血。
