OBJECTIVE: To evaluate the efficacy and safety of DCAG (decitabine, cytarabine, anthracyclines, and granulocyte colony-stimulating factor) regimen in the treatment of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). METHODS: The clinical data of 64 R/R AML patients received treatment at Chinese PLA General Hospital from January 1st, 2012 to December 31st, 2022 were retrospectively analyzed. Primary endpoints included efficacy measured by overall response rate (ORR) and safety. Secondary endpoints included overall survival (OS), event-free survival (EFS) and duration of response (DOR). The patients were followed from enrollment until death, or the end of last follow-up (June 1st, 2023), whichever occurred first. RESULTS: Sixty-four patients who failed prior therapy were enrolled and completed 1 cycle, and 26 and 5 patients completed 2 and 3 cycles, respectively. Objective response rate was 67.2% ［39: complete remission (CR)/CR with incomplete hematologic recovery (CRi), 4: partial remission (PR)］. With a median follow-up of 62.0 months (1.0-120.9), the median overall survival (OS) was 23.3 and event-free survival was 10.6 months. The median OS was 51.7 months (3.4-100.0) in responders (CR/CRi/PR) while it was 8.4 months (6.1-10.7) in nonresponders ( P <0.001). Grade 3-4 hematologic toxicities were observed in all patients. Four patients died from rapid disease progression within 8 weeks after chemotherapy. CONCLUSION The DCAG regimen represents a feasible and effective treatment for R/R AML.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Cytarabine/administration & dosage* ; Granulocyte Colony-Stimulating Factor/administration & dosage* ; Retrospective Studies ; Male ; Female ; Decitabine ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anthracyclines/administration & dosage* ; Middle Aged ; Adult ; Treatment Outcome ; Aged ; Recurrence

OBJECTIVE: To explore the efficacy and safety of venetoclax combined with demethylating drugs and intense chemotherapy in the treatment of acute myeloid leukemia (AML). METHODS: The clinical data of 76 patients with AML treated in Qilu Hospital of Shandong University Dezhou Hospital from January 2019 to March 2024 were retrospectively analyzed. Patients were divided into observation group and control group. 38 patients in the observation group received venetoclax combined with demethylating drugs (decitabine or azacytidine) and 38 patients in the control group with the "3+7" intensive chemotherapy regimen. The primary endpoints of clinical observation were complete remission (CR), CR with incomplete hematologic recovery (CRi), partial remission (PR), non remission (NR), and overall response rate (ORR). Secondary endpoints were overall survival (OS) and drug safety. RESULTS: After 2 courses of treatment, the CR+CRi rate in observation group and control group was 71.05% and 65.79%, respectively, and the ORR was 81.58% and 78.95%, respectively. After all courses of treatment, CR+CRi rate in the observation group and the control group was 73.68% and 78.95%, respectively, and the ORR was 81.58% and 84.21%, respectively, with no statistical significance between the two groups (P >0.05). After 1 course of treatment, there were statistically significant differences in the proportion and degree of myelosuppression, the duration of neutropenia and the duration of thrombocytopenia between the two groups (P < 0.05), while there were no statistically significant differences in the occurrence of neutropenia with fever between the two groups (P >0.05). The incidence of non-hematological adverse reactions was highest in infection (mainly pulmonary infection) and gastrointestinal reaction. Among the many adverse reactions, there were statistically significant differences in the infection and hypokalemia between the two groups (P < 0.05), the incidence of hypokalemia in observation group and control group was 42.11% and 15.79%, respectively, and the infection rate in observation group and control group was 73.68% and 94.74%, respectively. The median OS was 13.13(1.67-53.63) months in the observation group and 16.60(0.57-59.67) months in the control group. CONCLUSION The combination of venetoclax and demethylating drugs has a low degree of myelosuppression, but a long recovery time, a response rate as good as that of intensive chemotherapy, and a lower infection rate. However, the incidence of hypokalemia is low in the intensive chemotherapy regimen, and the regimen significantly improves the long-term outcome of patients.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Sulfonamides/therapeutic use* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Female ; Male ; Decitabine/therapeutic use* ; Azacitidine/therapeutic use* ; Middle Aged ; Treatment Outcome ; Adult ; Aged ; Remission Induction

OBJECTIVE: To investigate the short-term efficacy and safety of low-dose venetoclax combined with CHG (cytarabine+homoharringtonine+G-CSF) priming regimen in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy. METHODS: The data of 14 patients with AML or high-risk MDS admitted to the department of hematology/oncology of the First Hospital of Tsinghua University and 2 cooperative institutions from July 2022 to August 2023 were retrospectively analyzed. All the patients were treated with low-dose venetoclax combined with CHG priming regimen and the early induction (one course) efficacy and adverse reactions were observed. RESULTS: Among the 14 patients, 10 were males and 4 were females, with a median age of 69.5 (46-83) years. After 1 cycle of induction chemotherapy, the complete remission (CR) rate was 64.3% (9/14) and overall response rate (ORR) was 78.6% (11/14). Among the 10 patients with adverse prognosis according to cytogenetics and molecular genetics, the CR rate was 50.0% (5/10), and ORR was 70.0% (7/10). In 7 patients with TP53 mutation, the CR rate was 42.9% (3/7) and ORR was 71.4% (5/7). In the 6 patients with complex karyotype, CR rate was 33.3% (2/6) and ORR was 66.7% (4/6). While the CR rate and ORR of 8 non-complex karyotype patients were both 87.5% (7/8), and the difference in CR rate between patients with complex karyotype and non-complex karyotype was statistically significant ( P < 0.05). The adverse reactions of chemotherapy were tolerable, without early treatment-related deaths. CONCLUSION Low-dose venetoclax combined with CHG priming regimen can be used as an effective treatment for AML and high-risk MDS patients who are ineligible for intensive chemotherapy, and it is safe and worthy of clinical application.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Male ; Female ; Sulfonamides/therapeutic use* ; Middle Aged ; Myelodysplastic Syndromes/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Aged, 80 and over ; Retrospective Studies ; Cytarabine/administration & dosage* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Homoharringtonine/therapeutic use*

OBJECTIVE: To retrospectively analyze the clinical data of newly diagnosed acute myeloid leukemia (AML) patients treated with venetoclax combined with azacitidine (Ven/Aza) or standard "3+7" regimen and similar regimens, collect real-world study data, compare the treatment response and adverse events between the two regimens, as well as perform survival analysis. METHODS: To retrospectively analyze the efficacy, survival, and adverse reactions of newly diagnosed AML patients treated with Ven/Aza (24 cases) and "3+7" regimens (117 cases ) in our hospital from September 2009 to March 2023, as well as factors influencing outcomes. A propensity score matching (PSM) was performed on age and Eastern Cooperative Oncology Group performance status (ECOG PS) to obtain a 1:1 matched cohort of 20 pairs, and the efficacy and survival before and after the matching were compared. RESULTS: The median age of patients in the Ven/Aza group was 69 years, while that in the "3+7" group was 56 years (P <0.001). Objective remission rate (ORR) was 62.5% in Ven/Aza group and 74.8% in "3+7" group (P >0.05). The median overall survival (OS) in the Ven/Aza group was 522 days, while that in the "3+7" group was 1 002 days (P >0.05). After controlling the two variables of age and ECOG PS, a PSM cohort of 20 pairs was obtained, in which the ORR was 65% in Ven/Aza group and 60% in "3+7" group (P >0.05). The median OS was 522 days and 629 days, and median progression-free survival (PFS) was 531 days and 198 days between the two groups, respectively. There were no statistically significant differences in OS and PFS between the two groups (both P >0.05). Additionally, the incidence of adverse events in the Ven/Aza group was significantly reduced. CONCLUSION The overall cohort shows that the "3+7" regimen has advantages in efficacy and survival, but Ven/Aza regimen is relatively safer. After performing PSM on age and ECOG PS, the Ven/Aza group showed improved efficacy, and a longer median PFS compared to "3+7" group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Sulfonamides/administration & dosage* ; Azacitidine/administration & dosage* ; Bridged Bicyclo Compounds, Heterocyclic/administration & dosage* ; Aged ; Middle Aged ; Male ; Female ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome

OBJECTIVE: To investigate the clinical characteristics and prognostic of venetoclax (VEN) combined targeted therapy in acute leukemia (AL) patients with PICALM∷MLLT10 fusion gene positivity. METHODS: A retrospective analysis was conducted on 16 PICALM∷MLLT10-positive AL patients treated at the First Affiliated Hospital of Soochow University from January 2021 to August 2024. These patients were diagnosed by targeted RNA sequencing (RNA-seq) or reverse transcription multiplex PCR, including newly diagnosed and relapsed/refractory (R/R) cases. The immunophenotypes, genetic features, gene mutations, and the efficacy of VEN combination targeted therapy of patients were evaluated. RESULTS: Among the 16 cases, 3 were confirmed by reverse transcription multiplex PCR, and 13 were detected through targeted RNA-seq among 528 AL patients, with a detection rate of 2.46%. The averge age of patients was (28.0±8.58) years. Patients exhibited diverse immunophenotypes, including 7 cases of acute myeloid leukemia, 5 of acute T-lymphoblastic leukemia, 1 of acute B-lymphoblastic leukemia, 1 of acute undifferentiated leukemia, and 2 of mixed-phenotype acute leukemia. Among them, 11 had extramedullary disease (EMD), 14 expressed CD7, and 12 expressed CD33. Major co-occurring mutations included PHF6 (6 cases), NOTCH1 (5 cases), and 7 cases with complex karyotypes. Of the 12 patients who received standard induction therapy, 7 did not achieve remission (PR+NR). All 4 patients treated with VEN combination therapy achieved complete remission (CR). Among the 7 induction failure cases, 4 achieved CR upon re-induction with VEN, while the remaining 3 re-induced with standard therapy, did not achieve CR. Thirteen patients received allogeneic hematopoietic stem cell transplantation, including 6 who received maintenance therapy with hypomethylating agents (HMA) alone or in combination with VEN, and seven were followed up. Survival analysis showed that the overall survival was better in the maintenance therapy group (P =0.044). CONCLUSION PICALM∷MLLT10-positive AL involves multiple lineages and demonstrates poor response to conventional chemotherapy. VEN combination therapy shows promising efficacy in both newly diagnosed and R/R patients. Post-transplant maintenance therapy with HMA alone or combined with VEN may extend survival; however, further clinical validation is required.
Humans ; Sulfonamides/therapeutic use* ; Retrospective Studies ; Prognosis ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Adult ; Male ; Female ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

OBJECTIVE: To investigate the safety and efficacy of avatrombopag（AVA） combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia. METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups. RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups. CONCLUSION The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Thrombocytopenia/chemically induced* ; Interleukin-11/therapeutic use* ; Retrospective Studies ; Adult ; Thiophenes/therapeutic use* ; Platelet Count ; Female ; Male ; Middle Aged ; Thiazoles

Poor prognosis and high mortality rate are frequently observed in patients with relapsed/refractory acute myeloid leukemia (R/R AML), and there is no standard salvage therapy for these patients. As a method to evade apoptosis, cancer cells often upregulate anti-apoptotic proteins BCL-2 and MCL-1. Recently, venetoclax-based combination therapies have demonstrated promising prospects in treating R/R AML. However, the prevalent use of venetoclax comes with a new challenge of resistance. Upregulation of BCL-1 and/or MCL-1 is the main cause of venetoclax resistance and preemptively targeting BCL-2/BCL-XL/MCL-1 can be used to delay or forestall drug resistance. Thus, selective targeting of BCL-2 and MCL-1 is a viable treatment strategy. This review reports the latest clinical progress on targeting BCL-2 and MCL-1 in R/R AML.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Myeloid Cell Leukemia Sequence 1 Protein ; Proto-Oncogene Proteins c-bcl-2 ; Drug Resistance, Neoplasm ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Recurrence

OBJECTIVE: To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax, chidamide, and azacitidine in the treatment of elderly patients with acute myeloid leukemia (AML). METHODS: 15 elderly AML patients aged≥60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax, chidamide and azacitidine, and the efficacy, treatment-related adverse events, overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: After one course of treatment, 11 out of 15 patients achieved complete response (CR), 3 patients achieved CR with incomplete hematologic recovery (CRi), and 1 patient died due to prior infection before efficacy evaluation, and the overall response rate (ORR) was 93.3% (14/15). The median follow-up time was 131 (19-275) days, with median OS and EFS both remaining unreached. Next-generation sequencing (NGS) analysis showed that among the 15 patients, 13 were detected with gene mutations, and there were 7 genes with mutation frequencies of more than 10%, including ASXL1 (4 cases), RUNX1 (4 cases), BCOR (3 cases), DNMT3A (3 cases), STAG2 (2 cases), IDH1/2 (2 cases), and TET (2 cases). Among the 13 patients with detectable mutations, 12 patients achieved composite response (CR+CRi). The average recovery time of white blood cell count was 14.6 days after chemotherapy, and the average recovery time of platelets was 7.7 days after chemotherapy. The main adverse event was myelosuppression, with 10 patients accompanied by infection. Except for 1 patient who died due to septic shock during chemotherapy, no patients experienced serious complications such as heart, liver, or kidney damage during the treatment process. CONCLUSION The CACAG+V regimen, which combines the CAG regimen with venetoclax, chidamide, and azacitidine, can be applied in the treatment of elderly AML patients, demonstrating good safety and induction remission rate.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Aminopyridines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Azacitidine/therapeutic use* ; Aged ; Benzamides/therapeutic use* ; Male ; Female ; Treatment Outcome ; Middle Aged ; Cytarabine ; Aclarubicin ; Granulocyte Colony-Stimulating Factor

OBJECTIVE: To evaluate the efficacy and safety of PD-1 inhibitor combined with azacitidine and HAG regimen in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: This study is a prospective, single-arm, phase II clinical trial that included R/R AML patients who met the inclusion criteria and were treated at The First Affiliated Hospital of Soochow University from December 2020 to August 2023. Patients could undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) after salvage therapy. The efficacy and safety were evaluated. RESULTS: Twenty patients were enrolled, including 14 males and 6 females, with an average age of (50.7±15.3) years. The overall response rate (ORR) after one cycle of the treatment was 75.0% (15/20), and 35.0% (7/20) of the patients achieved complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after two cycles of the treatment. Eight patients received allo-HSCT. The main adverse events were hematologic toxicities, and no grade 5 adverse events occurred. CONCLUSION The combination of PD-1 inhibitor, azacitidine, and the HAG regimen is a feasible and relatively safe treatment option for R/R AML, thus, to be worth further study.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Azacitidine/administration & dosage* ; Male ; Female ; Middle Aged ; Prospective Studies ; Adult ; Hematopoietic Stem Cell Transplantation ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Programmed Cell Death 1 Receptor/antagonists & inhibitors* ; Aged

OBJECTIVE: To observe the efficacy and safety of 21-day venetoclax (VEN) plus azacitidine (AZA) (21-day VA) in newly diagnosed unfit acute myeloid leukemia (AML) patients in the real-world. METHODS: The clinical data of patients with unfit-AML who received 21-day VA regimen from December 2020 to July 2024 in our center and completed at least 1 cycle of therapeutic effect assessment was retrospectively collected to analyze the safety, efficacy and its influencing factors. RESULTS: A total of 59 patients were enrolled in our study, with a median age of 67(48-87) years old. After 1 cycle of therapy, the composite complete remission (cCR) rate was 74.5%, 54.2% of cases were negative for minimal residual disease (MRD). Among them, the MRD negative rate of patients with NPM1 mutation was significantly higher than that of patients without NPM1 mutation ( P =0.032). The median follow-up of patients was 19(2-38) months, the best cCR and MRD negative rates were 78% and 64.4%, respectively, the median overall survival (OS) time was 12 months, and the median progression free survival (PFS) time was 5 months. Multivariate Cox regression analysis showed less than 4 cycles of VA chemotherapy were independent risk factor for PFS and OS ( P < 0.05). After achieving remission, anemia and thrombocytopenia improved with the increase of the number of chemotherapy cycle. CONCLUSION In real-world, 21-day VA regimen still shows significant efficacy in the treatment of newly diagnosed unfit-AML, without adversely affecting remission rate and MRD negative rate of the first cycle.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Middle Aged ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Azacitidine/therapeutic use* ; Aged, 80 and over ; Male ; Female ; Retrospective Studies ; Nucleophosmin ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Remission Induction ; Mutation ; Treatment Outcome