Department of Hematology and Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA, USA
Department of Information Sciences, Division of Biostatistics, City of Hope, Duarte, CA, USA.
Haematologica. 2018 Oct;103(10):1662-1668. doi: 10.3324/haematol.2018.193599. Epub 2018 Jun 14.
Therapy-related acute lymphoblastic leukemia remains poorly defined due to a lack of large data sets recognizing the defining characteristics of this entity. We reviewed all consecutive cases of adult acute lymphoblastic leukemia treated at our institution between 2000 and 2017 and identified therapy-related cases - defined as acute lymphoblastic leukemia preceded by prior exposure to cytotoxic chemotherapy and/or radiation. Of 1022 patients with acute lymphoblastic leukemia, 93 (9.1%) were classified as therapy-related. The median latency for therapy-related acute lymphoblastic leukemia onset was 6.8 years from original diagnosis, and this was shorter for patients carrying the gene rearrangement compared to those with other cytogenetics. When compared to acute lymphoblastic leukemia, therapy-related patients were older (<0.01), more often female (<0.01), and had more gene rearrangement (<0.0001) and chromosomes 5/7 aberrations (=0.02). Although therapy-related acute lymphoblastic leukemia was associated with inferior 2-year overall survival compared to cases (46.0% 68.1%, =0.001), prior exposure to cytotoxic therapy (therapy-related) did not independently impact survival in multivariate analysis (HR=1.32; 95% CI: 0.97-1.80, =0.08). There was no survival difference (2-year = 53.4% 58.9%, =0.68) between the two groups in patients who received allogenic hematopoietic cell transplantation. In conclusion, therapy-related acute lymphoblastic leukemia represents a significant proportion of adult acute lymphoblastic leukemia diagnoses, and a subset of cases carry clinical and cytogenetic abnormalities similar to therapy-related myeloid neoplasms. Although survival of therapy-related acute lymphoblastic leukemia was inferior to cases, allogeneic hematopoietic cell transplantation outcomes were comparable for the two entities.
由于缺乏能够明确界定此类疾病的大型数据集，治疗相关性急性淋巴细胞白血病的定义仍不明确。我们回顾了 2000 年至 2017 年间在我院接受治疗的所有连续成人急性淋巴细胞白血病患者病例，并确定了治疗相关性病例——即先前接受细胞毒性化疗和/或放疗的急性淋巴细胞白血病患者。在 1022 例急性淋巴细胞白血病患者中，有 93 例（9.1%）被归类为治疗相关性。治疗相关性急性淋巴细胞白血病发病的中位潜伏期为首次诊断后 6.8 年，携带基因重排的患者潜伏期较其他细胞遗传学异常患者短。与急性淋巴细胞白血病相比，治疗相关性患者年龄较大（<0.01），女性比例较高（<0.01），且更多存在基因重排（<0.0001）和染色体 5/7 异常（=0.02）。尽管治疗相关性急性淋巴细胞白血病患者的 2 年总生存率较急性淋巴细胞白血病患者差（46.0% 68.1%，=0.001），但多因素分析显示，先前接受细胞毒性治疗（治疗相关性）并未独立影响生存（HR=1.32；95%CI：0.97-1.80，=0.08）。在接受异基因造血细胞移植的患者中，两组患者的生存无差异（2 年=53.4% 58.9%，=0.68）。综上所述，治疗相关性急性淋巴细胞白血病占成人急性淋巴细胞白血病诊断的很大比例，其中一部分病例存在与治疗相关性髓系肿瘤相似的临床和细胞遗传学异常。尽管治疗相关性急性淋巴细胞白血病的生存率低于急性淋巴细胞白血病，但异基因造血细胞移植的结果在这两种疾病中是可比的。
