Chidamide,Decitabine,Cytarabine,Aclarubicin,and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia:A Retrospective Study from a Single-Center

Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.

Impact of prophylactic/preemptive donor lymphocyte infusion and intensified conditioning for relapsed/refractory leukemia:a real-world study

Prophylactic/preemptive donor lymphocyte infusion(p/pDLI)and intensified conditioning have shown promising results in experimental studies of refractory/relapsed acute leukemia(RRAL),but real-world data remain scarce.We conducted a multicenter,population-based analysis of 932 consecutive patients.The three-year leukemia-free survival(LFS)rates were 56%for patients receiving both p/pDLI and intensified myeloablative conditioning(MAC)(intenseMAC)and 30%for those who received neither therapy per landmark analysis.Multivariable analyses were run separately for acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL),and p/pDLI treatment was linked to significantly higher LFS than non-DLI for both AML and ALL patients without increasing the nonrelapse mortality.IntenseMAC was associated with significantly lower relapse and higher LFS than nonintensified MAC despite higher nonrelapse mortality rates in ALL,while there was no impact of intenseMAC observed in AML.p/pDLI achieved superior outcomes in both matched-sibling donor(MSD)and haploidentical donor transplantation,while intenseMAC only influenced MSD outcomes.Data suggest that RRAL patients receiving“total therapy”by way of p/pDLI and intensified conditioning treatment have an improved chance for LFS,with p/pDLI being safer with a more extensive impact relative to intenseMAC.Patients with RRAL can tolerate both interventions and achieve a reasonable outcome.

Efficacy and Prognosis of Venetoclax Combined with Hypomethylating Agents in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Objective:To investigate the efficacy and prognosis of venetoclax combined with hypomethylating agents(HMAs)in the treatment of relapsed/refractory acute myeloid leukemia(AML).Methods:From June 2021 to February 2022,14 patients with relapsed/refractory AML were treated with venetoclax combined with HMAs,among which nine patients were treated with venetoclax+azacytidine,while five patients were treated with venetoclax+decitabine.The efficacy of the treatments was observed,and the patients were followed up.Results:All patients received one to five courses of treatment,in which the median course of treatment was three;four cases achieved CR and another four achieved PR,with NR in six cases;there was no treatment-related death.There were seven deaths up to the end of the follow-up period,all of which were progressive deaths at the end of the disease,and the overall survival rate was 50.00%.All the patients experienced different degrees of nausea,vomiting,and myelosuppression(Grade Ⅱ–Ⅳ),nine patients had Grade 3–4 hematological adverse reactions,and seven patients had infection.Conclusion:Venetoclax combined with hypomethylating agents is effective in the treatment of relapsed/refractory AML,with good prognosis,and some patients may even achieve CR.Although bone marrow suppression is serious with this combination,it is well tolerated.

CAGE Regimen in the Treatment of Adult Refractory Acute Non-Lymphocytic Leukemia

Objective:To observe the effect of CAGE regimen in the treatment of adult refractory acute non-lymphocytic leukemia.Methods:In this experiment,86 adult patients with refractory acute non-lymphocytic leukemia who were treated between January 2018 and January 2022 were selected as experimental subjects and were divided into two groups,the observation group and the control group,according to different treatment methods,with 43 patients in each group.The observation group was treated with the CAGE regimen,whereas the control group was treated with conventional therapy.The disease remission rate and incidence of adverse reactions were observed.Results:The comparison of disease remission rates between the two groups showed that there was no significant difference in the results of the first course of treatment and the second course of treatment between the two groups(P>0.05),but the incidence of adverse reactions in the observation group was lower than that in the control group(P<0.05).Conclusion:The CAGE regimen has a significant therapeutic effect in the treatment of adult refractory acute non-lymphocytic leukemia.It improves the treatment advantage of patients during the treatment process,thus alleviating the condition of patients and improving their quality of life.

Compound Zhebei granules combined with chemotherapy for the treatment of refractory acute leukemia: a randomized clinical trial

OBJECTIVE: To observe the effect of compound Zhebei granules(CZBG) with chemotherapy in the treatment of refractory acute leukemia.METHODS: In this multicenter, double-blind, placebo-controlled clinical trial, we used a central(online) randomization system to assign 235 patients to two treatment groups. A total of 118 patients received chemotherapy combined with CZBG(4 g,twice daily) and 117 patients received chemotherapy plus placebo. The clinical efficacy was evaluated at the end of one chemotherapeutic cycle.RESULTS: In the full analysis set, in which deaths due to disease progression were regarded as inefficacy, the rates of complete remission(CR) and partial remission(CR + PR) were 32.35% and 50.00%,respectively, for the chemotherapy combined with CZBG group, and 23.08% and 35.58%, respectively,for the chemotherapy plus placebo group. There was a statistically significant difference between the two groups according to a ysis set(PPχ2test(P < 0.05). In the per protocol analS), the CR(33.67%),CR+PR(52.04%) response rates for the chemotherapy plus CZBG group were significantly different from the response rates of the control group(CR:24.24% and CR+PR: 37.37%), respectively(P < 0.05).CONCLUSION: CZBG plus chemotherapy can improve the clinical remission rate of refractory acute leukemia after one just one therapeutic cycle.

Study on Effect of Chinese Herbal Medicine for Enhancing Therapeutic Efficacy on Refractory Drug Resistant Leukemia

The so-called multidrug resistance （MDR） of leukemic cells means the cross resistance of leukemic cells against multiple anti-tumor agents with different constitution and acting mechanism, which takes place simultaneous after resistance to a single contacted drug has been produced. Tumor cells with MDR would now show a low sensitivity to anti-tumor agents, making chemotherapy ineffective or of little effect. Moreover, MDR is one of the pathogenetic factors for inducing refractory leukemia.

Efficacy and safety analysis of the combination of cladribine,cytarabine,granulocyte colony stimulating factor( CLAG ) regime in patients with refractory or relapsed acute myeloid leukemia

Objective To analyze efficacy and safety of CLAG regimen in patients with refractory or relapsed acute myeloid leukemia(AML).Methods Efficacy and adverse events of patients with refractory or relapsed AML who were treated with one course of CLAG from April 1st,2014 through December 9th,2015 in our hospital were retrospectively reviewed.Results Thirty-three