High-throughput Drug Sensitivity Screening (HDS) Guided Treatment For Children With Refractory Or Relapsed Leukemia

Objective: We recorded the outcomes of High-throughput drug sensitivity screening(HDS)in children with refractory or relapsed(rel/ref)leukemia.We hope that as a new treatment scheme,it can provide basis for individualized treatment for children with rel/ref leukemia,formulate individualized treatment plans and provide opportunities for remission.As a bridging treatment before hematopoietic stem cell transplantation(HSCT),it can further improve the remission rate and quality of life.Methods: We recorded the clinical data of 84 children with rel/ref leukemia diagnosed in a single center.All the children with rel/ref AML were sent for high-throughput in vitro drug sensitivity testing.Under the premise of fully informing the treatment plan and risk,the children with rel/ref ALL should choose the empirical treatment according to the wishes of the patients’ family or the treatment based on the results of HDS testing,and the guardians signed the informed consent form.We observe the clinical data such as age,sex,genetic characteristics,diagnosis and treatment plan,curative effect during treatment,infection and complications and other clinical data.The curative effect and possible influencing factors were evaluated by retrieving the medical record system or following up by telephone for at least one year.Results: 1.General information: Cases were collected from children who were definitively diagnosed and treated in the Department of Pediatrics,the First Affiliated Hospital of University of Science and Technology of China,from January 2017 to December 2021.There were 37 cases(44%)of acute myeloid leukemia(AML)and 47cases(56%)of acute lymphoblastic leukemia(ALL).2.The results of rel/ref AML showed that: There were 18 males and 19 females,26 cases under 10 years old and 11 cases over 10 years old.The median age of patients was 5 years(range,1 to 15 years).Thirty-one patients were relapsed AML,29 of them early relapsed;6 patients were refractory AML.Twenty-four patients had adverse cytogenetics,and two patients had leukemia with central nervous system leukemia.Twenty-five patients’ bone marrow cytology reached complete remission(CR)after treatment,with the complete remission(CR)rate was 67.6%.Twenty-three patients(62.2%)had undergone HSCT,but 4patients were no remission(NR).There was no significant difference in the effects of age(P=0.740),sex(P=0.414)and disease classification(P=0.655)on bone marrow remission.All patients in this study developed bone marrow suppression after chemotherapy,8 of them developed grade Ⅳ bone marrow suppression.Severe liver function damage occurred in 9 children,but no renal function damage or heart failure occurred.Until November 30,2022,the median duration of follow-up were 15 months(range,0.5 to 58 months).The 3-year overall survival(OS)and the 3-year event-free survival(EFS)rate were 45.9% and 43.2%,respectively.Infection in myelosuppression stage was the main cause of death.3.The results of rel/ref ALL showed that: There were 11 males and 13 females in HDS group;the experience group consisted of 18 males and 5 females.The median ages of the two groups were 7 years old(HDS group,3 years old to 13 years of age)and 9 years old(experience group,1 year old to 13 years of age)respectively.Eight patients were diagnosed as T-ALL(HDS group 5 cases,experience group 3 cases),and 39 patients were diagnosed as B-ALL(HDS group 19 cases,experience group 20 cases).Twenty cases had bad cytogenetics,and 7 cases were complicated with extramedullary leukemia.There was no significant difference in age,sex,disease type,genetic characteristics and disease type between the two groups(P>0.05).Among all patients with relapsed ALL,the median time from relapse to treatment was 1 month(0.5 to 6 months),and 18 patients had early relapse,including 14 patients in HDS group and 4 patients in experience group.The difference between the two groups was significant(P=0.003).A total of 10 patients in HDS group developed grade Ⅲ-Ⅳ bone marrow suppression after treatment,and 9 patients in experience group developed grade Ⅲ-Ⅳ bone marrow suppression,which had no significant difference with HDS group(P=0.859).The occurrence of liver function abnormality and cardiac function damage was similar in the two groups(P>0.05),and the incidence of kidney function damage in the experience group was significantly higher than that in the HDS group(P=0.003).The bone marrow cytology of 12 patients in HDS group reached CR(50%),and that of 18 patients in the experience group reached CR(82.6%)after chemotherapy.There was a significant difference between the two groups(P=0.044).In HDS group,12 patients(50%)underwent HSCT after treatment,and one patient’s bone marrow did not reach CR for HSCT.In the experience group,16 patients(69.6%)underwent HSCT after remission.The median survival time of patients in the two groups was 5 months(HDS group,0.5 to 62 months)and 17 months(experience group,0.5 to 46 months),respectively.There was no significant difference in survival curves was observed between the two groups(OS P=0.366,EFS P=0.267).Conclusion: For children with rel/ref AML,the outcome of HDS was better than commonly reported rates,and has good safety.It may be a novel treatment option in paediatric patients with rel/ref AML.For children with ALL who are initially induced to remission,the original induction scheme can be continued to be selected to obtain a higher remission rate when relapse occurs.