Rosenthal N S, Farhi D C
University Hospitals of Cleveland, Institute of Pathology, Case Western Reserve University, Ohio 44106-5077, USA.
Am J Clin Pathol. 1996 Nov;106(5):676-9. doi: 10.1093/ajcp/106.5.676.
Cytopenias are typical of patients with connective tissue disease (CTD) and are usually related to autoimmune phenomena. In some cases, cytopenia may be the result of treatment with cytotoxic agents. Although multi-drug therapy is known to produce myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) in patients with CTD, treatment with single-agent therapy, particularly methotrexate, has rarely been associated with secondary MDS or AML. Blood and marrow samples were studied from 3 men and 5 women with rheumatoid arthritis (5 cases), Behcet's disease (2 cases), and systemic lupus erythematosus (1 case) developing MDS or AML after methotrexate (5 cases), chlorambucil (2 cases), and cytoxan (1 case). The durations of CTD ranged from less than 6 months to more than 10 years. Five patients (63%) presented with MDS including refractory anemia (RA), refractory thrombocytopenia (RT), refractory anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (CMML), and RAEB in transformation. Patients with RT, CMML, and RAEB in transformation developed AML. Of six patients presenting with or developing AML, four had AML with differentiation (FAB M2), one acute myelomonocytic leukemia (FAB M4), and one M4Eo. Inv 16 was seen in the M4Eo and t(8;21) in one case of M2. Four of six patients are alive up to 6 years after diagnosis of AML. One of three patients with MDS is alive 6 months after diagnosis of MDS. Cytopenias in patients with CTD may be due to therapy-related MDS or AML occurring in a setting of single-agent chemotherapy, including methotrexate.
血细胞减少是结缔组织病（CTD）患者的典型症状，通常与自身免疫现象有关。在某些情况下，血细胞减少可能是细胞毒性药物治疗的结果。虽然已知多药联合治疗会使CTD患者发生骨髓增生异常综合征（MDS）和急性髓系白血病（AML），但单药治疗，尤其是甲氨蝶呤治疗，很少与继发性MDS或AML相关。对3名男性和5名女性类风湿关节炎患者（5例）、白塞病患者（2例）和系统性红斑狼疮患者（1例）进行了血液和骨髓样本研究，这些患者在接受甲氨蝶呤（5例）、苯丁酸氮芥（2例）和环磷酰胺（1例）治疗后发生了MDS或AML。CTD的病程从不到6个月到超过10年不等。5名患者（63%）表现为MDS，包括难治性贫血（RA）、难治性血小板减少症（RT）、伴过多原始细胞的难治性贫血（RAEB）、慢性粒单核细胞白血病（CMML）和转化中的RAEB。RT、CMML和转化中的RAEB患者发展为AML。在6名出现或发展为AML的患者中，4例为分化型AML（FAB M2），1例为急性粒单核细胞白血病（FAB M4），1例为M4Eo。在M4Eo中发现inv 16，在1例M2中发现t(8;21)。6名AML患者中有4名在诊断AML后存活了6年。3名MDS患者中有1名在诊断MDS后存活了6个月。CTD患者的血细胞减少可能是由于单药化疗（包括甲氨蝶呤）导致的治疗相关MDS或AML。
