Miller K B, Kim K, Morrison F S, Winter J N, Bennett J M, Neiman R S, Head D R, Cassileth P A, O'Connell M J
Tufts New England Medical Center Hospital, Boston, MA 02111.
Ann Hematol. 1992 Oct;65(4):162-8. doi: 10.1007/BF01703109.
One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS.
在东部肿瘤协作组和西南肿瘤协作组联合开展的一项III期研究中，141例患者接受了评估低剂量阿糖胞苷（LDAC）与支持性治疗用于治疗骨髓增生异常综合征（MDS）的研究。患者被随机分为皮下注射阿糖胞苷10 mg/m²每日两次组或支持性治疗组。需要进行中心病理复查。所有患者均根据MDS的FAB标准进行分类。MDS亚型的总体符合率为52%，25例患者因病理原因被排除，其中20例为急性髓系白血病（AML）。LDAC单周期的总体缓解率为32%，完全缓解率为11%，部分缓解率为21%。中位缓解持续时间为5.9个月，范围为1.4 - 33.5个月。所有亚型均可见缓解。感染在LDAC组更为常见。接受LDAC或支持性治疗的患者在疾病进展时间或总生存期方面无差异。两组的白血病转化发生率相似，均为15%，但根据MDS亚型有所不同。接受LDAC治疗的患者在3个月后输血需求减少。接受单周期LDAC后细胞减少程度与生存之间存在显著相关性。这种生存差异在RAEB和RAEB - T亚型患者中最为明显。虽然LDAC在MDS的所有亚型中均产生了缓解，但对总生存期或转化为AML没有影响。然而，部分患者从单周期LDAC治疗中受益，缓解持久。持久缓解似乎需要细胞减少作用。未来的研究应包括病理复查，并且必须解决MDS的临床和生物学异质性问题。
