Objective:To evaluate the efficacy and safety of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage (ALAL) .Methods:A retrospective analysis of clinical data was performed on patients with newly diagnosed ALAL who were hospitalized at Jiangsu Provincial People's Hospital from June 2021 to July 2024. Of the 13 patients who received initial induction therapy with venetoclax combined with multidrug chemotherapy, 8 received VAA+P regimen, and 5 received V+IA regimen. Patients with FLT3 mutation were treated with FLT3 inhibitor, and Ph + patients received an additional tyrosine kinase inhibitor. Overall survival (OS), disease-free survival (DFS), and adverse events were analyzed. Results:According to the World Health Organization 5th edition of the classification of hematolymphoid tumors, the immunophenotypes were T/myeloid mixed-phenotype acute leukemia (MPAL) ( n=4), B/myeloid MPAL ( n=7), and ALAL- not otherwise specified ( n=2). Of the seven patients with B/myeloid MPAL, four were Ph + and belonged to the group with specific gene abnormalities of ALAL. Three patients had FLT3 mutation (one with FLT3-TKD mutation and two with FLT3-ITD mutation). Prior to the second course of consolidation therapy, the efficacy of venetoclax induction therapy was evaluated, and a complete response rate of 100% was achieved in 13 patients. In the subsequent consolidation therapy phase, one patient discontinued treatment and was lost to follow-up; nine patients underwent allogeneic hematopoietic stem cell transplantation, four of whom died due to posttransplant complications and five achieved DFS. Of the three patients (≥70 years old) who received consolidation therapy as before, two achieved DFS and one died due to central nervous system leukemia. The median OS time was not reached in 13 patients; the 75th percentile survival time was 12.0 months, with a 12-month cumulative survival rate of 64.5%. The median DFS time was not reached in all patients; the 75th percentile DFS time was 8.2 months, with a 12-month cumulative DFS rate of 67.1%. All patients experienced grade 3 or 4 hematologic toxicity, including neutropenia and thrombocytopenia, during and after induction therapy. All patients recovered hematopoietic function after the initial induction therapy, with no fatal hemorrhage, tumor lysis syndrome, neurological adverse events, or grade 3 or higher organ toxicity, excluding preexisting conditions. Conclusion:Venetoclax in combination with multidrug chemotherapy was effective and associated with tolerable adverse reactions in patients with newly diagnosed ALAL.

Objective:To evaluate the efficacy and safety of venetoclax in combination with multidrug chemotherapy in patients with newly diagnosed acute leukemia of ambiguous lineage (ALAL) .Methods:A retrospective analysis of clinical data was performed on patients with newly diagnosed ALAL who were hospitalized at Jiangsu Provincial People's Hospital from June 2021 to July 2024. Of the 13 patients who received initial induction therapy with venetoclax combined with multidrug chemotherapy, 8 received VAA+P regimen, and 5 received V+IA regimen. Patients with FLT3 mutation were treated with FLT3 inhibitor, and Ph + patients received an additional tyrosine kinase inhibitor. Overall survival (OS), disease-free survival (DFS), and adverse events were analyzed. Results:According to the World Health Organization 5th edition of the classification of hematolymphoid tumors, the immunophenotypes were T/myeloid mixed-phenotype acute leukemia (MPAL) ( n=4), B/myeloid MPAL ( n=7), and ALAL- not otherwise specified ( n=2). Of the seven patients with B/myeloid MPAL, four were Ph + and belonged to the group with specific gene abnormalities of ALAL. Three patients had FLT3 mutation (one with FLT3-TKD mutation and two with FLT3-ITD mutation). Prior to the second course of consolidation therapy, the efficacy of venetoclax induction therapy was evaluated, and a complete response rate of 100% was achieved in 13 patients. In the subsequent consolidation therapy phase, one patient discontinued treatment and was lost to follow-up; nine patients underwent allogeneic hematopoietic stem cell transplantation, four of whom died due to posttransplant complications and five achieved DFS. Of the three patients (≥70 years old) who received consolidation therapy as before, two achieved DFS and one died due to central nervous system leukemia. The median OS time was not reached in 13 patients; the 75th percentile survival time was 12.0 months, with a 12-month cumulative survival rate of 64.5%. The median DFS time was not reached in all patients; the 75th percentile DFS time was 8.2 months, with a 12-month cumulative DFS rate of 67.1%. All patients experienced grade 3 or 4 hematologic toxicity, including neutropenia and thrombocytopenia, during and after induction therapy. All patients recovered hematopoietic function after the initial induction therapy, with no fatal hemorrhage, tumor lysis syndrome, neurological adverse events, or grade 3 or higher organ toxicity, excluding preexisting conditions. Conclusion:Venetoclax in combination with multidrug chemotherapy was effective and associated with tolerable adverse reactions in patients with newly diagnosed ALAL.

This study aimed to assess the efficacy and safety of gilteritinib combined with chemotherapy in treating newly diagnosed FLT3-mutated acute myeloid leukemia (AML). We retrospectively collected clinical data from 16 patients newly diagnosed with FLT3-mutated AML at Jiangsu Province Hospital. Patients received induction therapy with the classic "3 + 7" regimen or the VA regimen, and all patients were immediately supplied with gilteritinib after detecting FLT3-ITD/TKD mutations. Of the 16 patients, 12 were male and 4 were female, with a median age of 52.5 years (range: 15-76 years). Additionally, 15 patients had FLT3-ITD mutations and 1 had FLT3-TKD mutation. The complete remission (CR/CRi) rate was 93.8% (15/16) after the first cycle of gilteritinib-based induction therapy, with 13 patients achieving MRD negativity detected with flow cytometry. All patients achieved a CR MRD- during the consolidation phase. FLT3 mutation clearance was achieved among all 14 patients who underwent next-generation sequencing (NGS) analysis. The 12-month overall survival and relapse-free survival rates were both 73.9%, respectively, with a median followup of 18 months. Nine (56.2%) patients experienced infectious fever during the induction therapy. Three patients had grade 3 QTc prolongation during consolidation and maintenance therapy. Treatment-related adverse events were generally tolerable.

This study aimed to assess the efficacy and safety of gilteritinib combined with chemotherapy in treating newly diagnosed FLT3-mutated acute myeloid leukemia (AML). We retrospectively collected clinical data from 16 patients newly diagnosed with FLT3-mutated AML at Jiangsu Province Hospital. Patients received induction therapy with the classic "3 + 7" regimen or the VA regimen, and all patients were immediately supplied with gilteritinib after detecting FLT3-ITD/TKD mutations. Of the 16 patients, 12 were male and 4 were female, with a median age of 52.5 years (range: 15-76 years). Additionally, 15 patients had FLT3-ITD mutations and 1 had FLT3-TKD mutation. The complete remission (CR/CRi) rate was 93.8% (15/16) after the first cycle of gilteritinib-based induction therapy, with 13 patients achieving MRD negativity detected with flow cytometry. All patients achieved a CR MRD- during the consolidation phase. FLT3 mutation clearance was achieved among all 14 patients who underwent next-generation sequencing (NGS) analysis. The 12-month overall survival and relapse-free survival rates were both 73.9%, respectively, with a median followup of 18 months. Nine (56.2%) patients experienced infectious fever during the induction therapy. Three patients had grade 3 QTc prolongation during consolidation and maintenance therapy. Treatment-related adverse events were generally tolerable.

Objective:To assess the efficacy of induction chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of FLT3-ITD + acute myeloid leukemia (AML) with normal karyotype. Methods:The clinical data of FLT3-ITD + AML patients with normal karyotype in the First Affiliated Hospital of Nanjing Medical University from Jan 2018 to March 2021 were retrospectively analyzed. Results:The study included 49 patients with FLT3-ITD +AML, 31 males, and 18 females, with a median age of 46 (16-59) years old. All patients received induction chemotherapy, and 24 patients received sequential allo-HSCT (transplantation group) . The median follow-up time was 465 days, the one-year overall survival (OS) from diagnosis was (70.0 ± 7.4) %, and one-year disease-free survival (DFS) was (70.3±7.4) %. The one-year OS was significantly different between the transplantation group and the non-transplantation group [ (85.2 ± 7.9) % vs (52.6 ± 12.3) %, P=0.049]. but one-year DFS [ (84.7 ± 8.1) % vs (55.2 ± 11.9) %, P=0.061] was not. No significance was found in one-year OS between patients with low-frequency and high-frequency FLT3-ITD + ( P>0.05) . There were 12 patients with high-frequency FLT3-ITD + in the transplantation and the non-transplantation groups, respectively. The one-year OS [ (68.8 ± 15.7) % in the transplantation group vs (26.2 ± 15.3) % in the non-transplantation group, P=0.027] and one-year DFS [ (45.5 ± 21.3) % in the transplantation group vs (27.8±15.8) % in the non-transplantation group, P=0.032] were significantly different between the two groups. Conclusion:Induction chemotherapy followed by allo-HSCT can enhance the prognosis of FLT3-ITD + patients, particularly those with FLT3-ITD high-frequency mutation.

Objective:To investigate the effect of obesity on the efficacy of allogeneic hematopoietic stem cell transplantation.Methods:The clinical data of 81 patients who underwent allogeneic hematopoietic stem cell transplantation from August 2017 to September 2020 in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. According to the body mass index (BMI), the patients were divided into the obese group (BMI≥28 kg/m 2, 11 cases) and the non-obese group (BMI<28 kg/m 2, 70 cases). The clinicopathological characteristics, hematopoietic stem cell implantation, post-transplantation complications, survival and recurrence were compared between the two groups. Univariate and multivariate survival analyses were performed by using Cox proportional hazards regression model. Results:The median follow-up time of 81 patients was 280 d (8-1 218 d). The 1-year overall survival (OS) rate was 77.9%, and the 1-year progression-free survival (PFS) rate was 73.8%. The 1-year OS rates of the non-obese group and the obese group were 82.6% and 46.2% ( χ2 = 15.54, P<0.01), and the 1-year PFS rates were 82.1% and 36.4% ( χ2 = 15.56, P<0.01). The non-recurrence mortality (NRM) rates of the non-obese group and the obese group were 7.1% and 32.7% ( χ2 = 6.463, P = 0.01), and the cumulative recurrence rate was 11.5% and 42.9% ( χ2 = 8.146, P = 0.004). Between the non-obese group and the obese group, the median engraft time of neutrophils and platelets, acute graft-versus-host disease, chronic graft-versus-host disease, hemorrhagic cystitis, cytomegalovirus infection and Epstein-Barr virus infection had no statistical difference ( P > 0.05). The result of multivariate analysis showed that obesity was an independent adverse influencing factor for OS of patients with allogeneic hematopoietic stem cell transplantation ( HR = 3.814, 95% CI 1.343-10.827, P = 0.012). Conclusion:Obesity is an important unfavorable factor that affects patient's survival after allogeneic hematopoietic stem cell transplantation, and the improvement of the efficacy and survival of these patients is worthy of further study.

Objective:To investigate the clinical features and prognosis of low triiodothyronine syndrome (LT3S) in patients with acute myeloid leukemia (AML) .Methods:A total of two 236 patients with AML who presented at the Jiangsu Provincial Hospital between January 2013 and December 2019 were included, and their data were retrospectively reviewed. The patients were divided into two groups, including the LT3S group and the non-LT3S group, according to their serum thyroxine level. The clinical characteristics and prognosis of the two groups were compared.Results:Among the 236 patients, 62 (26.3%) patients had LT3S. Serum-free T3 level was positively correlated with albumin ( r=0.443, P<0.001) and hemoglobin ( r=0.187, P=0.005) levels and negatively correlated with C-reactive protein ( r=-0.406, P<0.001) and lactate dehydrogenase ( r=-0.274, P<0.001) levels. The overall survival (OS) (7.5 months vs 29.9 months, P<0.001) and progression-free survival (PFS) (2.0 months vs 24.0 months, P<0.001) were significantly shortened in the LT3S group compared with the non-LT3S group. After propensity score matching, the OS (9.6 months vs 30.4 months, P=0.010) and PFS (3.0 months vs 30.0 months, P=0.014) were still significantly reduced in the LT3S group compared with the non-LT3S group. Therefore, LT3S was an independent risk factor for OS ( HR=2.553, 95% CI 1.666-3.912, P<0.001) and PFS ( HR=1.701, 95% CI 1.114-2.597, P=0.014) in patients with AML. Subgroup analysis suggested that patients with LT3S had a worse prognosis in patients with AML who were obese, fragile, or treated with standard chemotherapy. Conclusions:The occurrence of LT3S reflects the poor clinical status and prognosis of patients with AML.

OBJECTIVETo correlate the clinical features of patients with acute myeloid leukemia (AML) with mutations of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 genes as well as chromosomal aberrations.

METHODSSomatic mutations of aforementioned genes in 412 newly diagnosed AML patients were detected with PCR and direct sequencing. All patients were also subjected to R-banding chromosomal analysis. The results were correlated with the clinical features and prognosis of the patients.

RESULTSThe mutation rates of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 were 9.0% (26/289), 19.1% (50/262), 18.9% (34/180), 3.4% (7/208), 6.6% (9/137) and 6.9% (4/58), respectively. Patients with poor prognosis based on genetic mutations had lower blood platelet count than those with intermediate and good prognosis (P=0.001 and P=0.001, respectively). None of the three groups attained median overall survival (OS) (P> 0.05). The complete remission (CR) was similar among the three groups (P> 0.05). For patients with different prognosis based on cytogenetic findings, white blood cell count in those with intermediate prognosis was higher than those with good and poor prognosis (P< 0.001 and P=0.004, respectively), while the blood platelet count of the intermediate group was higher than that of the group with good prognosis (P=0.018). No significant difference was found among the three groups in terms of hemoglobin level (P> 0.05). The group with poor prognosis has attained shorter OS compared with those with good and intermediate prognosis (P< 0.001 and P=0.003, respectively). However, the CR rate of the group with good prognosis was higher than that of the intermediate group (P=0.001). For the group with intermediate prognosis, presence of genetic mutations did not correlate with the clinic characteristics such as white blood cell count, blood platelet count, hemoglobin level, OS and CR rate (P> 0.05 for all comparisons).

CONCLUSIONGenetic mutations combined with cytogenetic analysis can facilitate the prognosis and personalized treatment for patients with AML.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Leukemia, Myeloid, Acute ; genetics ; mortality ; Male ; Middle Aged ; Mutation ; Prognosis ; Young Adult

Elderly acute myeloid leukemia (AML) accounted for 35 % of all AML with the increased incidence year by year, and the median onset age is 67 years old. Generally, AML patients require strong chemotherapy, but older patients often cannot tolerate intense chemotherapy due to the viscera dysfunction. It is still lack of unified treatment clinically. Reports on treatment of elderly AML in the 57th American Society of Hematology (ASH) annual meeting covered multiple fields, in which the traditional induction chemotherapy, demethylation drug alone or in combination with other drugs, and novel drugs were an involved. This article reviewed the latest research on the elderly AML in the 57th ASH annual meeting.

OBJECTIVETo investigate the molecular mechanism of the growth inhibitory effect of matrine on K562 cells in JAK/STAT3 mediated signal pathway.

METHODSWestern blot analyses were performed to investigate the differential expression of JAK2, STAT3, phosphor-STAT3 (Tyr705 & Ser727) and phosphor-JAK2 proteins after matrine treatment in K562 cells with or without human recombinant interleukin 6 (IL-6) pretreatment. The expression of STAT3 response gene products such as Bcl-xL, Cyclin D1 and c-Myc, were investigated by Western blot and quantitative real time RT-PCR (qRT-PCR). Expression of IL-6, a potent upstream activating factor of JAK/STAT3 pathway, was analyzed by both real time qRT-PCR and ELISA.

RESUTLSWestern blot revealed that matrine treatment resulted in a strong down-regulation of phosphor-STAT3 both in Tyr705 and Ser727 sites or phosphor-JAK2 proteins expression without significant effects on the total STAT3 and JAK2 proteins. The expression of phosphor-Tyr705 STAT3 and phosphor-Ser727 STAT3 was decreased to 0.370 ± 0.172 in K562 cells treated with 0.5 mg/ml matrine for 48 h, respectively, from 0.690 ± 0.119 and 1.150 ± 0.263 in control cells, accompanied with a dramatical down-regulation of phosphor-JAK2 from 0.670 ± 0.137 to 0.049 ± 0.057 (P<0.05). In addition, it was found that the expression of Bcl-xL, Cyclin D1, c-Myc was decreased both at the transcription and protein level in K562 cells after matrine treatment. Matrine treatment resulted in a significant decrease in the expression level of IL-6 in K562 cells from (35.1 ± 1.93) to (10.74 ± 1.83) and (8.66 ± 1.24) pg/ml at the dose of 0.5 and 0.8 mg/ml, respectively (p<0.05). Matrine treatment could diminish the up-regulation of STAT3, JAK2, phosphor-STAT3 and phosphor-JAK2 protein following pretreatment with IL-6 in K562 cells.

CONCLUSIONMatrine exerts its anti-leukemia effect by interfering with the JAK2/STAT3 signaling pathway. The inhibition of IL-6 expression may play a pivotal role in the disruption of JAK/STAT pathway by matrine.

Alkaloids ; Down-Regulation ; Humans ; Interleukin-6 ; Janus Kinase 2 ; K562 Cells ; Quinolizines ; STAT3 Transcription Factor ; Signal Transduction ; Up-Regulation