Evaluation of the implementation rate of primary antifungal prophylaxis and the prognosis of invasive fungal disease in acute leukemia patients in China.
BACKGROUND
Invasive fungal disease (IFD) is a major complication of acute leukemia, thus primary antifungal prophylaxis (PAP) is recommended by guidelines. Nevertheless, guidelines might not be commonly followed in developing countries due to economic factors. The primary objectives were to evaluate the implementation rate of PAP in acute leukemia patients in China and to compare the prognosis of IFD with and without PAP. The secondary objectives were to investigate the safety of PAP, clinical characteristics of IFDs and risk factors of breakthrough.


METHODS
This was a retrospective observational single-center study, including non-M3 acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients receiving uniform induction or salvage chemotherapy between 2012 and 2016.


RESULTS
There were 29.4% of patients without PAP among a total of 248 cases. The incidence of breakthrough proven/probable/possible IFDs was 24.7%, 6.5%, 5.5%, 5.4% and 5.3% in control (no prophylaxis), fluconazole, itraconazole, voriconazole and posaconazole group respectively (P = 0.007), while the percentage of patients requiring empirical or pre-emptive therapy was 54.8%, 45.7%, 23.3%, 18.9%, 10.5% respectively (P < 0.001). PAP could also significantly improve IFD-free survival (P < 0.001) and reduce 90-day overall mortality in patients on AML salvage regimen (P = 0.021). There were no statistical differences in PAP-related adverse events. Past history of IFD (OR 9.5, P = 0.006) was confirmed to be independent risk factors.


CONCLUSIONS
There are a considerable number of acute leukemia patients without PAP in China, who have higher IFD incidence, increased empiric/pre-emptive antifungal drug use and worse IFD-free survival.
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: smartannie@163.com.
Xiao-Han
XH
Xu
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: pumczhanglu@163.com.
Lu
L
Zhang
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: caoxinxin@pumch.cn.
Xin-Xin
XX
Cao
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: lijian@pumch.cn.
Jian
J
Li
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: vv1223@vip.sina.com.
Wei
W
Zhang
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: zhutn@pumch.cn.
Tie-Nan
TN
Zhu
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: caihc@pumch.cn.
Hua-Cong
HC
Cai
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: chenm@pumch.cn.
Miao
M
Chen
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: xiaoer020@vip.sina.com.
Xiao
X
Han
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: yangchen@pumch.cn.
Chen
C
Yang
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: hanbing_li@sina.com.
Bing
B
Han
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: zhangyan10659@pumch.cn.
Yan
Y
Zhang
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: zhuangjunling@pumch.cn.
Jun-Ling
JL
Zhuang
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: daobinzhou@yahoo.comand.
Dao-Bin
DB
Zhou
Department of Haematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: mhduan@sina.com.
Ming-Hui
MH
Duan
D000293:Adolescent; D000328:Adult; D000368:Aged; D019072:Antibiotic Prophylaxis / Q000706:statistics & numerical data*; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001393:Azoles / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D000072742:Invasive Fungal Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology* / Q000517:prevention & control; D015470:Leukemia, Myeloid, Acute / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy; D055815:Young Adult
D000935:Antifungal Agents; D001393:Azoles
Acute leukemia; Azole; Induction chemotherapy; Primary antifungal prophylaxis; Salvage chemotherapy