Complete molecular response in CML after p210 BCR-ABL1-derived peptide vaccination
Complete molecular response in CML after p210 BCR-ABL1-derived peptide vaccination
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DOI：
10.1038/nrclinonc.2010.141
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发表时间：
2010-10-01
影响因子：
78.8
通讯作者：
Lauria, Francesco
中科院分区：
文献类型：
--
作者：
Bocchia, Monica;Defina, Marzia;Lauria, Francesco
背景。一名63岁的慢性髓性白血病（CML）妇女接受干扰素(IFN)- α治疗6年。在获得重复记录的完全细胞遗传学应答后，停止ifn - α治疗。尽管维持了完全的细胞遗传学应答，但在停止ifn - α治疗约2年后，检测到BCR-ABL1转录物的进行性上升，主要分子应答的丧失。疾病仍停留在分子水平。每3个月进行一次外周血实时荧光定量PCR及定期骨髓抽吸监测病情。慢性期，philadelphia阳性CML，在停止ifn - α治疗2年后仍可检测到完全细胞遗传学应答。患者接受靶向免疫方法治疗，接受治疗性疫苗，该疫苗由免疫原性25-mer b2a2断点衍生肽（CMLb2a2-25）组成，具有几种HLA-DR分子的结合特性。经过9次疫苗强化后，患者产生了足够的b2a2-25肽特异性CD4(+) t细胞反应，外周血中BCR-ABL1转录物开始下降。治疗期间无血液学或非血液学影响。在接种疫苗39个月后的最后一次评估中，患者处于完全的分子应答状态，外周血和骨髓中BCR-ABL1转录物水平均未检测到，并且作为唯一的治疗方法，她每3个月继续接受一次疫苗强化接种。
Background. A 63-year-old woman with chronic myeloid leukemia (CML) received treatment with interferon (IFN)-alpha for 6 years. After achieving a complete cytogenetic response that was repetitively documented, IFN-alpha treatment was stopped. Despite maintenance of a complete cytogenetic response, a progressive rise of the BCR-ABL1 transcript was detected and loss of major molecular response occurred about 2 years after stopping IFN-alpha therapy. Disease remained at molecular level.Investigations. Peripheral blood quantitative real-time PCR every 3 months and periodical bone marrow aspirate were performed to monitor disease.Diagnosis. Chronic-phase, Philadelphia-positive CML that was still detectable after complete cytogenic response 2 years after cessation of IFN-alpha therapy.Management. The patient was treated with a target immune approach receiving a therapeutic vaccine that consisted of an immunogenic 25-mer b2a2 breakpoint-derived peptide (CMLb2a2-25) with binding properties for several HLA-DR molecules. After nine boosts of vaccine the patient developed an adequate b2a2-25 peptide-specific CD4(+) T-cell response and BCR-ABL1 transcript started to decline in peripheral blood. No hematological or extrahematological effects were documented during therapy. At the last evaluation, 39 months since vaccinations commenced, the patient is in complete molecular response with an undetectable level of BCR-ABL1 transcript both in peripheral blood and in bone marrow and she continues to receive boosts of vaccine every 3 months as the only treatment.