关键词: 急性淋巴细胞白血病, 异基因移植, 费城染色体, BCR/ABL基因, 酪氨酸激酶抑制剂, 微小残留病, 早期干预, 复发

Abstract: BACKGROUND: BCR/ABL gene is a specific gene of Ph chromosome-positive acute lymphoblastic leukemia, and its expression level has become a sensitive indicator for monitoring minimal residual disease before and after allogeneic hematopoietic stem cell transplantation. However, whether the expression level of BCR/ABL gene before transplantation affects the efficacy of transplantation and how to guide the early intervention of relapse with tyrosine kinase inhibitors after transplantation is still inconclusive.
OBJECTIVE: To explore the relationship between BCR/ABL gene expression and recurrence in patients with Ph chromosome positive acute lymphoblastic leukemia before and after related and allogeneic hematopoietic stem cell transplantation.
METHODS: Twenty-four patients with Ph chromosome positive acute lymphoblastic leukemia who achieved complete hematological remission and underwent allogeneic hematopoietic stem cell transplantation were selected at the Affiliated Hospital of North China University of Science and Technology between January 2015 and December 2022. Real time fluorescence quantitative polymerase chain reaction was used to dynamically detect the expression levels of BCR/ABL genes during treatment, representing minimal residual disease. Based on BCR/ABL gene expression, tyrosine kinase inhibitors combined with chemotherapy was administered before transplantation to select the timing of allogeneic hematopoietic stem cell transplantation. After transplantation, the disease status was evaluated to guide the use of tyrosine kinase inhibitors, and an early intervention plan for recurrence was developed. 
RESULTS AND CONCLUSION: Follow-up was until December 2023, with a median follow-up time of 49 (12-82) months. There were 8 cases of hematological recurrence, with a median recurrence time of 14 (8-39) months and a cumulative recurrence rate of 33% (8/24). Univariate analysis showed that recurrence after allogeneic hematopoietic stem cell transplantation was not significantly correlated with gender, age, extramedullary complications, time from diagnosis to transplantation, HLA typing, acute graft-versus-host disease, and chronic graft-versus-host disease (P > 0.05). There was a significant correlation between the relief treatment course and minimal residual disease levels before transplantation. The second hematology completely resolution and positive minimal residual disease before transplantation had a higher hematological recurrence rate (P < 0.05). The 3-year cumulative recurrence rate, disease-free survival rate, and overall survival rate were 27%, 63%, and 74%; the 5-year cumulative recurrence rate, disease-free survival rate, and overall survival rate were 38%, 57%, and 74%, respectively. It is concluded that Ph chromosome positive acute lymphoblastic leukemia patients with BCR/ABL gene positive before transplantation have a higher recurrence rate. BCR/ABL gene expression after transplantation can guide the application of tyrosine kinase inhibitors and serve as a basis for early intervention in recurrence.

Key words: ">acute lymphoblastic leukemia, allogeneic transplantation, philadelphia chromosome, BCR/ABL gene, tyrosine kinase inhibitor, minimal residual disease, early intervention, recurrence