Objective To compare the efficacy and safety of venetoclax (VEN) in combination with chemotherapy (chemo) versus chemo alone in the treatment of acute myeloid leukemia (AML). Method To compare the efficacy and/or safety of VEN+chemo versus chemotherapy alone for AML, PubMed, Embase, Web of Science, and the Cochrane Library were used to searching up to June 2023. Comparisons included complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), overall response rate (ORR), and adverse events (AEs). Result A total of 9 articles were included, including 3124 patients. The baseline characteristics between two patient groups were similar. The combined analysis showed that compared with the group receiving chemo alone, the VEN+chemo group exhibited higher rates of CR, CRi, MLFS and ORR. Additionally, the VEN+chemo group had longer event-free survival (EFS) and overall survival (OS) durations. The incidence rates of AEs and serious AEs (SAEs) were similar between the two groups, but the early 30-day mortality rate was lower in the VEN+chemo group than in the chemo alone group. Conclusion The VEN+chemo therapy demonstrates significant efficacy and safety profile in AML patients. However, more prospective studies are needed in the future to provide more accurate and robust evidence for treatment selection in patients. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439288 , identifier CRD42023439288.
The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML. We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 109/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients. Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.
Abstract Multiple studies have confirmed the occurrence of second tumors as a rare incidence of CAR-T therapy, but one of the complications that does warrant in-depth exploration. According, given the relatively small number of reported second tumor types thus far, additional comprehensive occurrence and characterization of a new second tumor type after CAR-T therapy remains essential for understanding the risk of potential tumors with this therapy, as well as for defining the role of immune microenvironment in malignant transformation. In this article, a new second tumor type CMML was identified in a patient who had received CD19 CAR-T therapy for DLBCL. The immune microenvironment of both the pre- and post-treatment of secondary CMML and primary CMML were deeply profiled by ScRNA-seq. Our results demonstrated an enhanced inflammatory cytokines, chemokines, and immunosuppression state of monocytes/macrophages, which may inhibit the cytotoxicity of T/NKs in secondary CMML. In contrast, the cytotoxicity of T/NKs were enhanced in secondary CMML after treatment. Collectively, our results highlight a new type of second tumor, CMML after CAR-T therapy and provide a framework for defining the immune microenvironment of second tumor occurrence after CAR-T therapy. Our results also provide a rationale for targeting macrophages to strengthen CMML treatment.
To explore the characteristics of hemogram in patients with aplastic anemia (AA), especially mean corpuscular volume (MCV) and red cell distribution width (RDW). We examined the blood routine of 180 new-onset AA patients and used 166 patients with myelodysplastic syndrome (MDS) as controls. Among the 180 AA patients, 105 (58.3%) were diagnosed with severe AA (SAA), while 75 (41.7%) were diagnosed with non-severe AA (NSAA). Compared to MDS, patients with SAA generally had unfavorable hemogram, including significantly lower white blood cell (WBC), absolute neutrophil count (ANC), hemoglobin (Hb), platelet (PLT) and reticulocyte counts (RET). However, WBC, ANC and lymphocyte counts were higher in the NSAA group than in the MDS group; Hb and Ret were comparable between the two groups. 8.5% of SAA patients and 58.1% of NSAA patients presented with macrocytic anemia, whereas 25.7% of SAA and 64.0% of NSAA had a high RDW. In the MDS group, 54.7% of patients presented with macrocytic anemia, and 84.7% had increased RDW. WBC, ANC, PLT, and Ret in a high-RDW group (25.7% of SAA) were significantly higher than in a normal-RDW group (74.3% of SAA). Overall, most SAA patients exhibited normocytic–normochromic anemia, and their hemograms decreased more significantly; more than half of NSAA patients showed macrocytic-heterogeneous anemia, and their hemograms were similar to those of MDS. Patients with elevated RDW may have better residual bone marrow hematopoietic function than those with normal RDW but with more severe anemia.
Purpose: To investigate the prevalence, risk factors of intestinal carbapenem-resistant Enterobacteriaceae (CRE) colonization and bloodstream infection (BSI) caused by CRE in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: We analyzed the clinical data of 185 patients with hematological malignancies who underwent allo-HSCT from May 2019 to December 2021. All patients received regular CRE monitoring by rectal swab during allo-HSCT, and some CRE strains were further identified for carbapenemase phenotypes. The rates, distribution and risk factors of CRE colonization, CRE-induced BSI were analyzed. Results: CRE was detected in 44 of 185 recipients, with colonization rate of 23.8%. A total of 46 strains of CRE were isolated, including 22 Escherichia coli , 17 Klebsiella pneumoniae , three Klebsiella oxytoca , two Enterobacter hormaechei , and two other Enterobacteriaceae. Among the 19 strains identified with carbapenemase phenotypes, eight strains of E. coli produced metal β-lactamase, five K. pneumoniae produced serine carbapenemase, two K. pneumoniae produced metal β-lactamase, two K. oxytoca produced metal β-lactamase, a Citrobacter malonic acid-free produced metal β-lactamase and a Citrobacter freundii produced metal β-lactamase. In 10 patients developed with CRE-related BSI, the types and combined drug sensitivity of strains detected by rectal swab were highly consistent with blood culture. Multivariate analysis revealed that pulmonary infection, perianal infection and carbapenem application in the 3 months pre-transplant were independent risk factors for rectal CRE colonization, while rectal colonization with carbapenem-resistant K. pneumoniae (CR-KP) was an independent risk factor for CRE-induced BSI. The mortality rate within 30 days of CRE-related BSI was 50.0%, and patients receiving multi-drug therapy within 24 hours showed slightly lower mortality than that in the single-drug treatment group. Conclusion: Allo-HSCT patients with CRE-induced BSI have poor prognosis, and CR-KP rectal colonization is an independent risk factor for CRE-related BSI. Rectal swab screening during allo-HSCT could provide early warning for later CRE-induced BSI. Keywords: allogeneic hematopoietic stem cell transplantation, carbapenem-resistant enterobacteriaceae, bloodstream infection, intestinal colonization
Objective: The expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein and its regulation by chemotherapeutics were analyzed in primary acute leukemic cells.Materials and Methods: Peripheral blood was collected from 16 patients with acute leukemia on days 0, 1, 3, and 5 of chemotherapy.The mononuclear cells were separated from the peripheral blood, and TRAIL expression was assessed by flow cytometry.The bone marrow mononuclear cells of patients with acute leukemia were separated before chemotherapy and cultured in vitro with VP-16 and/or interferon (IFN).The TRAIL expression level was detected after the cell culture.Results: TRAIL expression in the mononuclear cells of peripheral blood was significantly upregulated on day 1 (p<0.05)and then significantly decreased on day 5 after chemotherapy (p<0.05).Results from the in vitro culture revealed that VP-16 upregulated TRAIL expression in the bone marrow mononuclear cells of patients with acute leukemia, but the binding of VP-16 to IFN did not enhance TRAIL expression as compared with VP-16 alone (p>0.05). Conclusion:OA single chemotherapy mechanism for leukemia may suffice to induce TRAIL expression and promote the apoptosis of leukemic cells.
Objective
To investigate the clinical features and prognosis of patients with acute leukemia (AL) in pregnancy.
Methods
The clinical data of 39 cases of acute leukemia in pregnancy at the First Affiliated Hospital of Zhengzhou University from January 2010 to April 2017 were collected. The clinical characteristics and prognosis were analyzed retrospectively.
Results
Except one case diagnosed before pregnancy, the incidence rates of AL in early, middle and late stage of pregnancy were 23.7% (9/38), 52.6% (20/38) and 23.7% (9/38), respectively. 31 patients received chemotherapy and the complete response (CR) rates of AL patients in early, middle and late stage of pregnancy were 71.4% (5/7), 94.1% (16/17), and 100.0% (7/7), respectively. Among all the cases, 31 patients received a miscarriage or induction of labor, and 8 cases had live births delivered by cesarean section. Twenty-two patients had abnormal karyotypes, which was mainly related to specific chromosomal rearrangement. Acute myeloid leukemia (AML) patients expressed high levels of CD117, CD13, CD33, and CD38, and acute lymphoblastic leukemia (ALL) patients had high expression of CD19, CD38, CD22, cCD79a, and CD58. After induction therapy, 10 cases got positive minimal residual disease (MRD), 7 of which achieved CR. After that, 4 cases recurred, and 7 cases died in total. On the other hand, all the 19 MRD-negative patients achieved CR. Then, 5 cases recurred, and 9 cases died in total. In all patients, 29 were AML while the other 10 were ALL, the CR rates in AML and ALL were 95.7% (22/23) and 75.0% (6/8), and the 1-year and 2-year survival rate were 53.1% and 26.4%, respectively. The survival rate of AML patients was higher than that of ALL patients.
Conclusions
The clinical characteristics of AL patients in pregnancy are complicated and comprehensive treatment is needed. MDR is an important indicator of prognosis, and the prognosis of ALL is worse than that of AML.
Key words:
Leukemia; Pregnancy; Treatment; Prognosis
To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS).The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (＜60 years old) were compared.The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ2=7.180, P=0.007) and (20.0% vs 6.7%) ( χ2=8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ2=16.653, P=0.000) and (23.6% vs 8.7%)(χ2=9.041, P=0.003) respectively.The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.基于二代测序的老年和年轻成人急性髓系白血病患者突变基因谱比较.比较基于二代测序（NGS）的老年和年轻急性髓系白血病（AML）患者突变基因谱，探讨老年AML的分子生物学特点.回顾性分析2018年1月至2018年11月在郑州大学第一附属医院进行了基于22个基因突变谱的NGS检测初治AML（非急性早幼粒细胞白血病）患者的突变基因数据，并比较老年（≥60岁）和年轻（＜60岁）AML患者之间的差异.250例患者常见突变频率依次为NPM1（22.4%）、FLT3-ITD（18.8%）、NRAS（17.2%）、DNMT3A（14.4%）、TET2（11.6%）、IDH2（9.6%）、CEBPA双突变（8.8%）、CEBPA单突变（8.4%）、KIT（8.4%）、RUNX1（7.6%）、IDH1（7.6%）、ASXL1（6.0%）、U2AF1（5.2%）、SRSF2 （3.2%）、SF3B1（3.2%）、TP53（2.4%）、KRAS（2.0%）。NPM1、CEBPA 、DNMT3A突变常见于患者预后中等组，而KIT突变在患者预后良好组更常见。老年患者较年轻患者更多出现TET2突变（21.8% vs 8.7%）（χ2=7.180，P=0.007）和IDH2突变（20.0% vs 6.7%）（χ2=8.788，P=0.003）。将突变基因按照功能进行分组显示，老年患者更多发生DNA甲基化和去甲基化突变（包括DNMT3A、TET2、IDH1、IDH2）（67.3% vs 36.4%，χ2=16.653，P=0.000），以及RNA剪切酶突变（包括SRSF2、SF3B1 、U2AF1、ZRSR2）（23.6% vs 8.7%）（χ2=9.041，P=0.003）.基于NGS技术发现，不同年龄的AML患者常见突变种类存在显著差异，老年患者更多发生DNA甲基化和去甲基化突变以及RNA剪切酶突变.
Objective To research the curative effect and adverse reactions of bortezomib in the treatment of newly diagnosed and relapsed or refractory multiple myeloma(MM).Methods Thirty-two patients including 21 newly diagnosed multiple myeloma patients and 11 relapsed or refractory multiple myeloma(RRMM)patients.Twenty-one patients were treated with BTD regimen,it consisted of bortezomib(1.0-1.3 mg/m2) by rapid intravenous injection on the 1 st,4 th,8 th and 11th day,and dexamethasone 20 mg/d by intravenous drip(day 1-4) or 10 mg/d by intravenous drip(day 1-4,day 9-12,day 17-20),and oral thalidomide (100-200 mg/d) was given for the whole course.Nine patients received BD regimen,usage as same as the former.Two patients were treated with PAD regimen,adriamycin(9 mg/m2) was used on dayl-4,other usage as same as the former.All regimen were repeated,every 21 days as one cycle.Response to Bortezommib was assessed according to the criteria of European Group for Blood and Marrow Transplantation,and adverse reaction were evaluated according to the criteria of National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0.The prognosis factors were analysed by chi-square test and Spearman rank correlation.Results The total clinical response(CR + nCR + PR + MR) was 90.6％,newly diagnosed patients compared with RRMM patients,the difference was significant (P =0.27).The total better response (CR + nCR + PR) was 71.8 ％,compared the two groups,the difference was significant (P =0.04).The total complete response (CR) was 71.8％,the difference was significant between the two groups (P =0.12).The total near complete response(CR + nCR) was 56.2％,the difference was significant between the two groups (P =0.03).The correlation coefficient of course and remission level was 0.60,the difference was significant (P ＜ 0.01).The major adverse events during treatment were blood hypocellular(56％),gastrointestinal disorder (49％),peripheral neuropathy (32％),systemic symptom (27％).Three patients got herpes zoster and one got rash.Conclusions Bortezomib based chemotherapy was well tolerated and effective in treatment of multiple myeloma,even newly diagnosed or RRMM patients.
Key words:
Bortezomib ; Multiple myeloma; Efficacy ; Adverse events
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