Division of Rheumatology, Department of Internal Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey.
Division of Hematology, Department of Internal Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey.
Clin Rheumatol. 2018 Dec;37(12):3419-3425. doi: 10.1007/s10067-018-4242-8. Epub 2018 Jul 28.
Low-dose methotrexate (ld-MTX) that is administered during rheumatoid arthritis (RA) treatment has hematological adverse effects such as pancytopenia, although rare. Although well-established and widely used for hematological adverse effects caused by high-dose MTX, leucovorin (folinic acid) treatment does not have an agreed-upon administration for ld-MTX-induced pancytopenia. Here, we aimed to figure out whether there was any difference in response time between the regimens with and without folinic acid prescribed to our patients who developed pancytopenia while on MTX therapy, and to identify risk factors for its development. Our cases were collectively assessed together with other rare cases available in the literature that were reported in a similar manner with an explicitly indicated response time, in days. Thereupon, we looked for any difference in response time between the regimens with and without folinic acid. In total, ten of our patients experienced pancytopenia while on ld-MTX treatment. Mean day on which hematological response was achieved was as follows: 7 days in one patient on folic acid monotherapy, 6 days in three patients on granulocyte-colony stimulating factor (G-CSF) monotherapy, 4.5 days in two patients on leucovorin monotherapy, and 4 days in the remaining three patients who were treated with G-CSF + folinic acid/leucovorin. When we collectively evaluated our patients and the patients with an explicitly stated response duration in the literature (15 patients) and compared regimens including folinic acid to those without folinic acid, duration until response/recovery from pancytopenia was significantly shorter in folinic acid group than that in the group without folinic acid (5.47 ± 2.9 days vs 10 ± 3.77 days, p = 0.002). Treatment modalities including folinic acid (leucovorin) either with or without G-CSF result in a shorter recovery/response time compared to other agents. Leucovorin should definitely be considered and applied in rescue therapy for ld-MTX-associated side effects.
低剂量甲氨蝶呤（ld-MTX）在类风湿关节炎（RA）治疗期间会产生血液学不良反应，如全血细胞减少症，尽管这种情况很少见。尽管甲酰四氢叶酸（leucovorin，folinic acid）治疗对于高剂量 MTX 引起的血液学不良反应已得到充分确立并广泛应用，但对于 ld-MTX 引起的全血细胞减少症，尚无公认的治疗方案。在这里，我们旨在确定在接受 MTX 治疗的患者中发生全血细胞减少症时，接受或不接受甲酰四氢叶酸治疗的方案之间的反应时间是否存在差异，并确定其发生的危险因素。我们的病例与文献中以类似方式报告的其他罕见病例一起进行了综合评估，并明确指出了反应时间（以天为单位）。随后，我们比较了接受和不接受甲酰四氢叶酸治疗的方案之间的反应时间是否存在差异。总共有 10 名患者在接受 ld-MTX 治疗时出现全血细胞减少症。达到血液学反应的平均天数如下：1 名患者接受甲酰四氢叶酸单药治疗为 7 天，3 名患者接受粒细胞集落刺激因子（G-CSF）单药治疗为 6 天，2 名患者接受甲酰四氢叶酸单药治疗为 4.5 天，其余 3 名患者接受 G-CSF+甲酰四氢叶酸/甲酰四氢叶酸治疗为 4 天。当我们综合评估我们的患者和文献中明确给出反应持续时间的患者（15 名患者），并比较包括甲酰四氢叶酸的方案与不包括甲酰四氢叶酸的方案时，发现甲酰四氢叶酸组从全血细胞减少症恢复/反应的时间明显短于无甲酰四氢叶酸组（5.47±2.9 天比 10±3.77 天，p=0.002）。包括甲酰四氢叶酸（leucovorin）在内的治疗方式，无论是否联合 G-CSF，与其他药物相比，恢复/反应时间更短。对于 ld-MTX 相关副作用的解救治疗，肯定应该考虑并应用甲酰四氢叶酸。
