Besa E C, Kunselman S, Nowell P C
Department of Medicine, Allegheny University Hospitals MCP Division, Philadelphia, PA 19129, USA.
Leuk Res. 1998 Aug;22(8):741-9. doi: 10.1016/s0145-2126(98)00057-5.
A pilot study was performed to determine the efficacy of 13-cis-retinoic acid (CRA) and alpha-tocopherol (AT) with increasing doses of recombinant human erythropoietin (rHuEPO) in anemic patients with primary myelodysplastic syndrome (MDS), to determine response rate and to determine the dose requirement and long-term effects of rHuEPO therapy on the transition to acute non-lymphocytic anemia and survival of these patients. Twenty-four consecutive MDS patients were entered into the study. Patients were stratified according to their FAB classification at study entry. Therapy consisted of a 6 month trial of CRA (100 mg m(-2) day(-1) and AT (800 mg day(-1)) with rHuEPO (150 units kg(-1) body weight subcutaneously three times a week). The rHuEPO dose was escalated to daily doses at 2 months, and 300 U kg(-1) body weight given three times a week for another 2 months and continuing therapy after 6 months in responsive patients. Response was measured by elimination of transfusions requirement (partial response, PR) and normal hemoglobin level and complete blood counts (complete response, CR). Observed responses for the 23 evaluable patients were 2 CR and 6 PR (34.8%). Odds ratio analysis showed that patients with anemia alone were 14 times more likely to respond than patients with pancytopenia (p = 0.06). In our study, two patients (8%) transformed to acute leukemia in CRA + AT + rHuEPO-treated patients. Median survival of 34 months with a median follow-up of 17 months (range 3-70 months) was observed. The response rates with the addition of rHuEPO to CRA and AT was similar but occurs earlier at 2 months compared to 6-10 months with CRA and AT alone and did not alter survival. There was no increase in the risk for leukemia in the group treated with rHuEPO. Response to either therapy appeared to be limited to patients in the early stages of MDS.
开展了一项初步研究，以确定13-顺式维甲酸（CRA）和α-生育酚（AT）联合递增剂量的重组人促红细胞生成素（rHuEPO）对原发性骨髓增生异常综合征（MDS）贫血患者的疗效，确定缓解率，并确定rHuEPO治疗对这些患者向急性非淋巴细胞性贫血转变及生存的剂量需求和长期影响。24例连续的MDS患者纳入本研究。患者在研究入组时根据其FAB分类进行分层。治疗包括为期6个月的CRA（100 mg m(-2) 每日）、AT（800 mg每日）联合rHuEPO（150单位/千克体重，皮下注射，每周3次）试验。rHuEPO剂量在2个月时增至每日剂量，并在接下来的2个月给予300 U/千克体重，每周3次，对有反应的患者在6个月后继续治疗。通过消除输血需求（部分缓解，PR）、正常血红蛋白水平和全血细胞计数（完全缓解，CR）来衡量反应。23例可评估患者的观察到的缓解情况为2例CR和6例PR（34.8%）。比值比分析显示，单纯贫血患者的反应可能性是全血细胞减少患者的14倍（p = 0.06）。在我们的研究中，接受CRA + AT + rHuEPO治疗的患者中有2例（8%）转化为急性白血病。观察到中位生存期为34个月，中位随访时间为17个月（范围3 - 70个月）。CRA和AT联合rHuEPO的缓解率相似，但与单独使用CRA和AT时6 - 10个月相比，在2个月时更早出现，且未改变生存期。接受rHuEPO治疗的组中白血病风险没有增加。对任何一种治疗的反应似乎仅限于MDS早期阶段的患者。
