[Breakthrough of invasive fungal disease with posaconazole as primary prophylaxis after induction chemotherapy for acute myeloid leukemia].

Objective: To investigate the breakthrough incidence of invasive fungal disease(IFD) and side effects of posaconazole as primary prophylaxis during induction chemotherapy for acute myeloid leukemia(AML). Methods: A total of 206 newly diagnosed AML patients admitted to our department during January 2016 and December 2018 were enrolled in the study. Exclusive criteria were as followings including patients diagnosed as acute promyelocytic leukemia; those who received intravenous antifungal therapy after admission or had history of IFD one month before induction chemotherapy, or those with functional insufficiency of vital organs and those older than 65. Forty-seven patients received posaconazole (posaconazole group), 61 cases received voriconazole (voriconazole group) and 98 cases did not receive any prophylaxis (control group) during induction chemotherapy. Prophylactic efficacy and safety between posaconazole and voriconazole were compared. Results: During induction chemotherapy, five possible cases of IFD occurred in posaconazole group (10.6%); while 11 cases (18.0%) were in voriconazole group including 7 possible, 3 probable and 1 proven. Thirty-five cases (35.7%) in control group were diagnosed as IFD including 19 possible, 11 probable and 5 proven ones. The incidences of IFD in posaconazole and voriconazole group were significantly lower than that in control group (P<0.05). The difference of posaconazole group and voriconazole group was not significant (P>0.05). The reported adverse events in posaconazole group were significantly lower than those in voriconazole group [12.8%(6/47) vs. 32.8%(20/61), P<0.05]. Conclusions: Posaconazole and voriconazole decrease IFD as primary prophylaxis during induction chemotherapy in patients with AML. The prophylactic effect of IFD with posaconazole is similar as voriconazole, but posaconazole shows better safety.

[Ikaros family zinc finger 1 mutation is a poor prognostic factor for adult Philadelphia chromosome positive acute lymphoblastic leukemia].

Objective: To analyze the prognostic impact of Ikaros family zinc finger 1(IKZF1) mutation on adult Philadelphia chromosome (Ph1) positive acute lymphoblastic leukemia (ALL) patients. Methods: IKZF1 mutation was detected in 63 adult Ph1 positive ALL patients at diagnosis using capillary electrophoresis. Recruited patients were treated in our center and other three hospitals in Ningbo from January 2014 to January 2017. Clinical data were collected and retrospectively analyzed. Results: Thirty-nine (61.9%) patients were positive IKZF1 mutation in this cohort. The white blood cell (WBC) count in IKZF1 mutation group was significantly higher than that of mutation negative group [(64.6±11.3)×10(9)/L vs. (33.7±5.6)×10(9)/L, P<0.05]. Patients with WBC count over 30×10(9)/L accounted for 56.4% in IKZF1 mutation group. Complete remission (CR) rate in the IKZF1 mutation group was also lower than that of negative group after induction chemotherapy (64.1% vs. 75.0%, P>0.05). IKZF1 was a negative prognostic factor but not independent factor for survival by univariate and multivariate analyses. Patients were divided into chemotherapy and allogeneic transplantation groups. The 3-year overall survival (OS) rate and 3-year leukemia-free survival (LFS) rate in IKZF1 mutation group were significantly lower than those of negative group in both transplantation group (42.3% vs. 59.3%; 31.2% vs. 50.0%; respectively, both P<0.05) and chemotherapy group (24.8% vs. 40.0%; 19.0% vs. 34.3%; respectively, both P<0.05). Conclusion: IKZF1 mutation is a poor prognostic factor for adult Ph1 positive ALL patients.

[Effect of FLT3-ITD with DNMT3A R882 double-mutation on the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M(3) and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group. Results: ①Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M(0), 24 cases of M(1), 56 cases of M(2), 39 cases of M(4), 63 cases of M(5), 6 cases of M(6) and 12 unclassified cases. ②All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD(+) DNMT3A R882(+) group (group A), FLT3-ITD(+) DNMT3A R882(-) group (group B), FLT3-ITD(-) DNMT3A R882(+) group (group C) and FLT3-ITD(-) DNMT3A R882(-) groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (P>0.05). ③The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, P<0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, P<0.05]. Conclusion: AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.

[Clinical features and prognostic analysis of high-risk acute promyelocytic leukemia patients].

OBJECTIVE: To investigate the clinical features and outcomes of high-risk acute promyelocytic leukemia (APL) patients. METHODS: A retrospective analysis was conducted to compare the clinical characteristics and prognosis of 118 high-risk APL patients (WBC≥10 × 10(9)/L) and 234 low and intermedia-risk patients (WBC <10×10(9)/L) from January 2003 to April 2015, who were treated in the First Affiliated Hospital of Zhejiang University and Yinzhou People's Hospital affiliated to Medical College of Ningbo University. RESULTS: The initial platelet counts of high-risk APL were significantly lower than that of low and intermediate-risk groups (P=0.003); the major type of PML-RARα isoforms in high-risk patients was short-form (51.8% vs 28.2%, P <0.001); the early death (ED) rate of high-risk patients was higher than low and intermedia-risk patients (20.3% vs 2.6%, P<0.001); in contrast, the complete remission (CR) rate and 5 years estimated overall survival (OS) rate of the former were lower than the latter (76.3% vs 94.9%, P <0.001; 74.2% vs 93.7%, P <0.001). However, the CR rate (P=0.682) and 5 years estimated OS rate (P=0.481) did not have difference when the ED patients were excluded. The 5 years estimated relapse-free survival (RFS) and central nervous system (CNS) relapse were 82.7%, 9.4%, respectively, which were lower than low and intermediate-risk groups (87.8%, 1.4% ) with statistic difference (P=0.048, 0.002). High-dose cytarabine and intrathecal chemotherapy may reduce the risk of CNS relapse. CONCLUSION: The outcomes of high-risk APL patients were worse than low and intermediate-risk group owing to the high ED rate and CNS relapse, it was important to decrease the ED rate and emphasis the CNS prophylaxis for high-risk APL patients.