Efficacy of Venetoclax Plus Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia Patients with FLT3-ITD Mutation / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITDmut R/R AML) and analyze the molecular genetic characteristics of the patients.@*METHODS@#Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITDmut R/R AML were analyzed.@*RESULTS@#14.3% (1/7) of the patients in FLT3-ITDmut group and 22.2% (2/9) of the patients in FLT3-ITDwt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITDmut group and FLT3-ITDwt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITDmut patients was significantly shorter than that of FLT3-ITDwt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITDmut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA.@*CONCLUSION@#VEN plus AZA showed a certain effect on patients with FLT3-ITDmut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITDmut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.

Detection of rearrangements of mixed lineage leukemia gene and its clinical significance / 中国实验血液学杂志

To study the incidence, the types of fusion genes and the clinical significance of rearrangements of mixed lineage leukemia (MLL) gene in acute leukemia (AL), the rearrangements of MLL gene of 60 patients with AL were detected by fluorescence in situ hybridization (FISH) and 6 types of common fusion genes resulting from the rearrangements of MLL gene were detected by nested RT-PCR. The results showed that 7 out of 60 AL patients were found the rearrangements of MLL gene, the incidence of which was 11.67%. 2 out of 7 patients were diagnosed as AML-M(5), 5 patients were diagnosed as B-ALL. The fusion genes of the 2 AML-M(5) patients who had the rearrangements of MLL gene were MLL/AF(9). Among 5 B-ALL patients, 2 patients were confirmed to express MLL/ENL, 1 patient was confirmed to express MLL/AF(4), the other 2 patients did not express the fusion genes. It is concluded that FISH is a fast, specific and sensitive method to detect the rearrangements of MLL gene in AL patients and nested RT-PCR is a convenient and feasible method to detect the types of fusion genes resulting from the rearrangements of MLL gene. The detection of MLL gene rearrangement is of great importance in predicting prognosis and guiding therapy in AL.