Analysis Of Severe Adverse Reactions Of CCCG-ALL-2015 Protocol Treated In Pediatric Acute Lymphoblastic Leukemia

Objective:From January 2015 to December 2018,629 children with acute lymphoblastic leukemia(ALL)were diagnosed and treated with CCCG-ALL-2015 regimen in our hospital.The purpose of this study was to evaluate the safety of CCCG-ALL-2015 regimen in the treatment of children with ALL,and to analyze the chemotherapy stage,type and related risk factors of severe adverse reactions(SAE).Methods:Between January 2015 to December 2018,629 children(younger than 18-year-old)with newly diagnosed ALL and treated with CCCG-ALL-2015 protocol in our hospital were enrolled in this study.According to the risk group defined by the protocol,different intensity treatment schemes were developed.SAE defined by the protocol included:(1)septic shock:persistent hypo-tension occurred on the basis of sepsis,and vasoactive drugs were needed to maintain blood pressure after full volume resuscitation;(2)severe pneumonia:pneumonia with other organ damage such as respiratory failure,intestinal paralysis or gastrointestinal bleeding,shock,convulsion or consciousness changes,renal insufficiency;(3)severe hemorrhage related to treatment:intracranial hemorrhage,pulmonary hemorrhage,other hemorrhage need urgent blood transfusion;(4)serious allergic reaction:anaphylactic shock caused by drug,acute laryngitis with obvious obstruction or allergic asthma;(5)severe abdominal viscera infection:abdominal viscera infection with intestinal perforation,peritonitis or shock;(6)Other adverse reactions requiring transfer to ICU.Results:1)629 children with ALL completed chemotherapy with a total number of 2120.Among them,45 children occurred with 54 cases of SAE,and the overall incidence was 2.6%.The incidence of SAE was highest in the induction remission stage(4.8%,n=30),followed by the interphase and reinduction stage(2.8%,n=14).2)Septic shock,severe pneumonia and severe bleeding were the most common SAE,accounting for 90.7%of all SAE,among which septic shock accounted for 35.2%(n=19),severe pneumonia accounted for 31.5%(n=17),and severe bleeding accounted for 24.1%(n=13).3)Age less than 1-year-old or more than10 years old,and WBC more than 50×10~9/L at initial diagnosed are independent risk factors for SAE(P<0.05).4)23 children died for SAE,and the treatment-related mortality(TRM)was 3.7%.And infection-related mortality(IRM)was 2.7%,accounting for74.0%of TRM(n=17),and bleeding factors accounted for 21.7%(n=5).Conclusions:It is relatively safety to apply the CCCG-ALL-2015protocol to treatment children with ALL,with an incidence of SAE of 2.6%and TRM of 3.7%,similar to international reports.SAE mainly occurred in the stage of remission induction therapy.Age and WBC at initial diagnosed were independent risk factors for SAE.