Shuravina E N, Parovichnikova E N, Demidova I A, Misiurin A V, Isaev V G, Ol'shanskaia Iu V, Savchenko V G
Ter Arkh. 2006;78(7):25-31.
To study efficacy of different programs of maintenance therapy, to create the program of differential therapy of minimal residual disease (MRD) and molecular recurrences at all stages of acute promyelocytic leukemia (APL) basing on the results of monitoring.
A total of 76 APL patients entered the trial. They received therapy by the protocols APL-97/98, APL-01, AIDA, 5D. Expression of chymeric oncogen PML/RARa in the disease onset was estimated by bone marrow and/or peripheral blood examination with RT-PCR. The study of chymeric oncogen PML/RARa was made once in two months.
The program of differential therapy of APL is proposed on the basis of molecular-biological monitoring of expression of chymeric oncogen PML/RARa. The results of molecular monitoring of MRD correlated with development of molecular and hematological recurrences. Therapeutic policy is determined after diagnosis of molecular recurrence. Further therapy of APL is determined which allows a rise in overall and recurrence-free survival of the patients.
The efficacy of maintenance therapy only with cytostatic drugs or their combination with ATRA is similar. The response to biological therapy with ATRA plus interferon-alpha is not sufficient. Molecular recurrences--probable or documented--are detected in maintenance therapy 2 months earlier, on the average, than hematological ones. Changes in the treatment policy in registration of molecular recurrence significantly diminish probability of hematological recurrence (from 36 to 0%, p = 0.001.
研究不同维持治疗方案的疗效，根据监测结果制定急性早幼粒细胞白血病（APL）各阶段微小残留病（MRD）和分子复发的差异化治疗方案。
共有76例APL患者进入试验。他们按照APL - 97/98、APL - 01、AIDA、5D方案接受治疗。通过骨髓和/或外周血RT - PCR检测疾病初发时嵌合癌基因PML/RARa的表达。每两个月对嵌合癌基因PML/RARa进行一次检测。
基于对嵌合癌基因PML/RARa表达的分子生物学监测，提出了APL的差异化治疗方案。MRD的分子监测结果与分子和血液学复发的发生相关。在诊断分子复发后确定治疗策略。确定了进一步的APL治疗方案，可提高患者的总生存率和无复发生存率。
仅使用细胞毒性药物或其与全反式维甲酸（ATRA）联合进行维持治疗的疗效相似。ATRA加α干扰素的生物治疗反应不足。在维持治疗中，分子复发（可能或已证实）平均比血液学复发早2个月被检测到。分子复发确诊时治疗策略的改变显著降低了血液学复发的概率（从36%降至0%，p = 0.001）。
