Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid:: Result of the randomized MRC trial
Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid:: Result of the randomized MRC trial
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DOI：
10.1182/blood.v93.12.4131.412k12_4131_4143
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发表时间：
1999-06-15
期刊：
影响因子：
20.3
通讯作者：
Goldstone, AH
中科院分区：
文献类型：
--
作者：
Burnett, AK;Grimwade, D;Goldstone, AH
全反式维甲酸（ATRA）是治疗急性早幼粒细胞白血病（APL）的重要组成部分，但最佳时机和持续时间仍有待确定。这种疾病的分子特征可以完善诊断，并可能在监测治疗反应中有潜在的用途。形态学上定义为APL的患者被随机分为两组，一组在开始化疗前接受为期5天的ATRA治疗，另一组在化疗开始后每天接受ATRA治疗，直至完全缓解（CR）。化疗是目前MRC白血病试验中使用的化疗。结果比较是通过意向治疗与相关风险因素的额外分析。通过t（15;17）融合产物的分子技术对患者进行表征，并在治疗期间和治疗后通过逆转录-聚合酶链反应（RT-PCR）进行监测。延长ATRA治疗导致上级缓解率（87% v70%，P <0.001），这是由于早期和诱导期死亡较少（12% v23%，P = 0.02），耐药疾病较少（2% v7%，P = 0.03），这与中性粒细胞和血小板明显更快的恢复有关。扩展ATRA降低了复发风险（4年时20% vs36%，P = 0.04），并导致了上级的生存率（4年时71% vs52%，P = 0.005）。表现为白色血细胞计数（WBC）是结局的关键决定因素。WBC低于10 x 10（9）/L的患者中，70%的患者CR率更高（85% vs62%，P = .0001），复发风险降低（22% vs42%，P = .002），生存率上级（69% vs43%，P < .0001）。在低计数组中，扩展ATRA导致更好的CR（94% v76%，P = 0.001），降低复发风险（13% v35%，P = 0.04），并改善生存率（80% v57%，P = 0.0009），没有证据表明WBC较高（>10 x 109/L）的患者获益。第三个化疗疗程后的分子监测与复发风险相关。如果RT-PCR阳性，复发风险为57%，如果PT-POP阴性，复发风险为27%（P = .006）。APL患者谁目前与低白细胞获得大量的好处，从联合ATRA诱导化疗，直到达到缓解，而白细胞较高的患者没有受益。疾病的分子特征可以提高诊断精度，巩固后阳性RT-PCR可识别复发风险较高的患者。(C)1999年，美国血液学会。
All-trans retinoic acid (ATRA) is an essential component of the treatment of acute promyelocytic leukemia (APL), but the optimal timing and duration remain to be determined. Molecular characterization of this disease can refine the diagnosis and could be potentially useful in monitoring response to treatment. Patients defined morphologically to have APL were randomized to receive a 5-day course of ATRA before commencing chemotherapy or to receive daily ATRA commencing with chemotherapy and continuing until complete remission (CR). The chemotherapy was that used in current MRC Leukaemia Trials. Outcome comparisons were by intention to treat with additional analysis for relevant risk factors. Patients were characterized by molecular techniques for the fusion products of the t(15;17) and monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) during and after treatment, Two hundred thirty-nine patients were randomized. Treatment with extended ATRA resulted in a superior remission rate (87% v 70%, P < .001), due to fewer early and induction deaths (12% v 23%, P = .02), and less resistant disease (2% v 7%, P = .03), which was associated with a significantly more rapid recovery of neutrophils and platelets. Extended ATRA reduced relapse risk (20% v 36% at 4 years, P = .04) and resulted in superior survival (71% v 52% at 4 years, P = .005). Presenting white blood cell count (WBC) was a key determinant of outcome. The 70% of patients who presented with a WBC less than 10 x 10(9)/L had a better CR (85% v 62%, P = .0001) and reduced relapse risk (22% v 42%, P = .002) and superior survival (69% v 43%, P < .0001). Within the low count group, extended ATRA resulted in a better CR (94% v 76%, P = .001), reduced relapse risk (13% v 35%, P = .04), and improved survival (80% v 57%, P = .0009), There was no evidence of benefit in patients presenting with a higher WBC (>10 x 109/L). Molecular monitoring after the third chemotherapy course had a correlation with risk of relapse. The relapse risk was 57% if the RT-PCR was positive versus 27% if the PT-POP was negative (P = .006). APL patients who present with a low WBC derive substantial benefit from combining ATRA with induction chemotherapy until remission is achieved, whereas patients with a higher WBC did not benefit. Molecular characterization of disease can improve diagnostic precision and a positive RT-PCR after consolidation identifies patients at a higher risk of relapse. (C) 1999 by The American Society of Hematology.