81例Ph染色体阳性急性淋巴细胞白血病患者的遗传学特征及疗效分析

Genetic Characteristics and Curative Effect Analysis of 81 Patients with Ph Chromosome Positive Acute Lymphoblastic Leukemia

摘要: 目的：研究Ph染色体阳性急性淋巴细胞白血病(Ph⁺ALL)患者的遗传学特征，分析影响患者疾病缓解和复发以及患者生存状况的因素。方法：收集2002年1月至2020年5月期间于青大附院初诊的Ph+ALL患者共81例，收集患者的一般资料、遗传学相关检查、治疗方案等，分析不同遗传学特点和不同治疗方案患者的病情转归及生存状况。结果：81例患者中有46例(56.79%)患者为P210基因阳性，有34例(41.98%)患者为P190基因阳性，1例(1.23%)患者同时存在P190和P210基因阳性。在随访期内发生ABL激酶突变的患者有15例(18.25%)，P210融合基因组的突变率为10.87%，P190融合基因组的突变率为29.41%，二者有显著性统计学差异(P = 0.036)。有42例患者在第一次诱导缓解化疗中加用酪氨酸激酶抑制剂(TKIs)，该组患者的缓解率为69.05%，有39例患者在第一次诱导缓解治疗中单用传统化疗方案，缓解率为43.59%，二者有显著性统计学差异(P = 0.021)。随访期内获得完全缓解的患者有69例，其中伊马替尼治疗组的复发率为61.70%，达沙替尼治疗组的复发率为31.82%，二者有显著性统计学差异(P = 0.021)。根据患者的治疗方案进行分组，比较各组患者的生存曲线，其中伊马替尼治疗组和达沙替尼治疗组(P = 0.003)、随访期内行造血干细胞移植(HSCT)组和未移植组(P = 0.010)的生存曲线不同。结论：在Ph⁺ALL患者中，P210比P190更多见。BCR/ABL融合基因为P190可能为ABL激酶突变的危险因素。第一次诱导缓解化疗即加用TKIs的患者比单用传统化疗方案治疗的患者有更高的缓解率。伊马替尼治疗组的复发率高于达沙替尼治疗组的复发率。选用达沙替尼治疗、完全缓解后行HSCT治疗可以改善患者的生存状况。

Abstract: Objective: To study the genetic characteristics of patients with Phchromosome positive acute lymphoblastic leukemia (Ph⁺ALL) and to analyze factors that influence remission and recurrence of the disease and survival of the patients. Methods: There are 81 patients who were initial diagnosed with Ph+ALL in their first visiting the Affiliated Hospital of Qingda University from January 2002 to May 2020. We collected their general information, genetic tests and treatment plans and analyzed the prognosis and survival status of patients with different genetic characteristics and treatment plans. Results: Among the 81 patients, 46 (56.79%) cases have P210 gene, 34 (41.98%) cases have P190 gene, and 1 (1.23%) case has both P190 and P210 gene. During the follow-up period, there were 15 patients (18.25%) generating ABL kinase mutation, the mutation rate of P210- cases is 10.87%, and P190-case is 29.41%, showing a statistically significant difference (P = 0.036). There were 42 patients being treated with tyrosine kinase inhibitors (TKIs) in the first induction chemotherapy, with a remission rate of 69.05%, and 39 patients being treated with conventional chemotherapy alone, with a remission rate of 43.59%, showing a statistically significant difference (P = 0.021). There were 69 patients who achieved complete remission during the follow-up period, among which the recurrence rate of the imatinib-treatment group is 61.70% and that of the Dasatinib-treatment group is 31.82%, showing statistically significant difference (P = 0.021). Patients were grouped according to their treatment regimen and the survival curves of patients in each group were compared. The survival curves of the imatinib-treatment group and dasatinib-treatment group (P = 0.003), the hematopoietic stem cell transplantation (HSCT) group and the non-trans- plantation group are different (P = 0.010). Conclusion: In Ph⁺ALL, P210 is more common than P190. P190 may be a risk factor for ABL kinase mutation. Patients treated with TKIs for the first induction therapy had higher remission rates than those treated with conventional chemotherapy alone. The recurrence rate of the imatinib group was higher than that of the dasatinib group. The survival of patients treated with dasatinib and treated with HSCT after complete remission can be improved.