Objective:To evaluate the predictive value of simplified geriatric assessment (sGA) in elderly Chinese patients diagnosed with diffuse large B-cell lymphoma (DLBCL) .Methods:It retrospectively analyzed the relationships of sGA with the clinical characteristics, outcome, and prognosis of 219 patients aged ≥60 years who were newly diagnosed with DLBCL at six hospitals in Jiangsu province between January 2018 and December 2022.Results:The median age of 219 patients was 68 years (60-87 years). According to the sGA system criteria, 101 (46.1%), 103 (47.0%), and 15 (6.8%) elderly patients with DLBCL were categorized as fit, unfit, and frail, respectively. The most common adverse reactions after chemotherapy were hematologic, and the incidence of grade >2 hematologic adverse reactions was similar among the three groups (47.5% vs 41.7% vs 46.7%, respectively; χ2=0.712, P=0.700). Compared with the fit and unfit groups, the frail group showed tendencies toward for higher proportions of grade >2 gastrointestinal, pulmonary, and infectious adverse reactions ( P>0.05 for all). The fit, unfit, and frail groups had respective remission rates of 74.3%, 46.6%, and 20.0% ( χ2=25.249, P<0.001) ; disease progression rates of 5.9%, 11.7%, and 26.7% ( χ2=6.763, P<0.05) ; 2-year overall survival rates of 92.1% (95% CI 86.6% to 97.9%), 77.6% (95% CI 69.5% to 86.6%), and 70.1% (95% CI 49.4% to 99.6%) ( P<0.05) ; and 2-year progression-free survival rates of 76.8% (95% CI 67.0% to 84.8%), 69.7% (95% CI 61.8% to 82.0%), and 65.7% (95% CI 53.3% to 100%) ( P=0.399) . Conclusion:sGA can effectively predict treatment adverse effects and efficacy, disease progression, and long-term survival in elderly DLBCL.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To evaluate the predictive value of simplified geriatric assessment (sGA) in elderly Chinese patients diagnosed with diffuse large B-cell lymphoma (DLBCL) .Methods:It retrospectively analyzed the relationships of sGA with the clinical characteristics, outcome, and prognosis of 219 patients aged ≥60 years who were newly diagnosed with DLBCL at six hospitals in Jiangsu province between January 2018 and December 2022.Results:The median age of 219 patients was 68 years (60-87 years). According to the sGA system criteria, 101 (46.1%), 103 (47.0%), and 15 (6.8%) elderly patients with DLBCL were categorized as fit, unfit, and frail, respectively. The most common adverse reactions after chemotherapy were hematologic, and the incidence of grade >2 hematologic adverse reactions was similar among the three groups (47.5% vs 41.7% vs 46.7%, respectively; χ2=0.712, P=0.700). Compared with the fit and unfit groups, the frail group showed tendencies toward for higher proportions of grade >2 gastrointestinal, pulmonary, and infectious adverse reactions ( P>0.05 for all). The fit, unfit, and frail groups had respective remission rates of 74.3%, 46.6%, and 20.0% ( χ2=25.249, P<0.001) ; disease progression rates of 5.9%, 11.7%, and 26.7% ( χ2=6.763, P<0.05) ; 2-year overall survival rates of 92.1% (95% CI 86.6% to 97.9%), 77.6% (95% CI 69.5% to 86.6%), and 70.1% (95% CI 49.4% to 99.6%) ( P<0.05) ; and 2-year progression-free survival rates of 76.8% (95% CI 67.0% to 84.8%), 69.7% (95% CI 61.8% to 82.0%), and 65.7% (95% CI 53.3% to 100%) ( P=0.399) . Conclusion:sGA can effectively predict treatment adverse effects and efficacy, disease progression, and long-term survival in elderly DLBCL.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To explore the coexisting gene mutations of FLT3-ITD mutation and its association with partial clinical parameters in acute myeloid leukemia (AML).Methods:The clinical data of 236 newly diagnosed AML outpatients and hospitalized patients of Changzhou No.2 People's Hospital and the Second People's Hospital of Wuxi between December 2012 and August 2019 were retrospectively analyzed. Genome DNA-polymerase chain reaction (PCR) combined with Sanger sequencing was used to detect FLT3-ITD mutations, and 51 tumor target gene mutations in patients with FLT3-ITD mutations were detected by using high-throughput DNA sequencing combined with Sanger sequencing.Results:Among 236 AML patients, FLT3-ITD mutations were found in 71 cases (30.1%). About 97.2% (69/71) patients with FLT3-ITD mutations were accompanied by additional mutations, of which 19 patients harbored double coexisting genes mutations, 24 patients harbored 3 coexisting genes mutations and 26 patients harbored ≥ 4 coexisting genes mutations. The most common coexisting genes mutations were NPM1 (55 cases, 77.5%), followed by DNMT3A (36 cases, 50.7%), TET2 (9 cases, 12.7%), CEBPA (5 cases, 7.0%), IDH1 (4 cases, 5.6%) and NRAS (4 cases, 5.6%). In FLT3-ITD mutation group, the hemoglobin level of patients with DNMT3A mutation type was lower than that of those with DNMT3A wild type ( t = -2.37, P = 0.020); the hemoglobin level of patients with NPM1 mutation type was higher than that of those with NPM1 wild type ( t = 2.04, P = 0.045). The platelet in patients with 3 mutations and ≥ 4 mutations was higher than that in those with double mutations ( χ2 = 7.72, P = 0.021). After chemotherapy in 71 patients, the curative effect of 66 cases was evaluable, and the white blood count of 18 patients who did not reach complete remission was higher than that of 48 patients who reached complete remission ( Z = -2.74, P = 0.006). Conclusions:Most FLT3-ITD mutated patients with AML commonly show coexisting gene mutations, and the mutation types of coexisting genes are correlated with the clinical features of patients.

Objective To detect ASXL1 gene variants among patients with myelodysplastic syndrome (MDS) and explore their correlation with variants of other genes and clinical features of patients.Methods For 149 patients with MDS,genomic DNA was amplified by PCR and subject to direct sequencing to identify variants of ASXL1,U2AF1,SF3B1,DNMT3A,TET2,IDH1/2,NPM1,FLT3-ITD and C-KIT genes.Results ASXL1 variants were found among 37 patients (24.8％).Other commonly mutated genes included U2AF1 (22.8％),TET2 (11.4％),DNMT3A (9.4％),NPM1 (8.1％) and SF3B1 (6.0％).The frequency of concurrent U2AF1 and TET2 variants among patients with ASXL1 variants was slightly higher than that of wild-type patients.No significant difference was found in median age,MDS subtype,karyotype,peripheral leukocytes,hemoglobin,platelet levels,and bone marrow blast counts between the ASXL1-variant and the wild-type groups (P＞0.05).Twenty-nine patients harboring ASXL1 variants were followed up,37.9％ progressed to acute myeloid leukemia (AML).The rate of transformation in ASXL1-variant group was significantly higher than the wild-type group (37.9 ％ vs.14.1％,P＜0.01).Conclusion ASXL1showed a high frequency of variant among MDS patients,which was frequently accompanied with U2AF1 and TET2 variants.Compared with the wild type group,patients with ASXL1 variants were more likely to progress to AML.

OBJECTIVE: To characterize the mutational profile of patients with core-binding factor acute myeloid leukemia (CBF-AML). METHODS: A total of 81 acute myeloid leukemia patients were recruited, which included 36 cases of CBF-AML and 45 cases of cytogenetically normal acute myeloid leukemia (CN-AML) . Mutations of FLT3-ITD, FLT3-TKD, NPM1, c-KIT, NRAS, KRAS, TET2, IDH1/2, RUNX1, DNMT3A, GATA2, ASjXL1, TP53, PTPN11, JAK2V617F, SETBP1 and CEBPA genes were simultaneously detected by DNA-based PCR and Sanger sequencing. RESULTS: Over all, mutations were detected in 68 patients (83.9%), with the most common ones including double CEBPA mutations (n=17), followed by NPM1 (n=15), c-KIT (n=11), NRAS (n=10), TET2 (n=9), FLT3-TKD (n=9), FLT3-ITD (n=8), IDH1 (n=7), RUNX1 (n=7), KRAS (n=7), DNMT3A (n=6), IDH2 (n=4), and GATA2 (n=4) mutations. AML1-ETO and CBFβ-MYH11 fusions were present in 21 and 15 patients, respectively. Coexistence of ≥2 mutations was more common in CN-AML comparing with CBF-AML. The mutation rate of NPM1, FLT3-ITD, DNMT3A, IDH1 and CEBPA double mutations were higher in patients with CN-AML. NRAS, c-KIT and KRAS mutations were identified more frequently in patients with CBF-AML (P<0.05). Based on the function, aberration of genes involved in DNA methylation, NPM1 proteins and transcription predominated in CN-AML, while tyrosine kinase receptor signaling and RAS pathways have predominated in CBF-AML. CONCLUSION The genomic landscape of CBF-AML patients has differed from that of CN-AML patients. Synergy of fusion genes with particular mutations may impact the clinical phenotype and prognosis of patients.
Core Binding Factors ; genetics ; DNA Mutational Analysis ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Mutation ; Prognosis

OBJECTIVE: To characterize the molecular genetics of 81 patients with acute monocytic leukemia (AML). METHODS: Fluorescence in situ hybridization (FISH) was employed to detect MLL gene rearrangements. Combined mutations of 17 genes were detected by DNA-based PCR and Sanger sequencing. RESULTS: Sixty seven patients were found to harbor at least one mutation. The most commonly mutated gene was NPM1 (n=18), which was followed by FLT3-ITD (n=16), NRAS (n=16), DNMT3A (n=15), TET2 (n=12), RUNX1 (n=11) and KRAS (n=9). Based on the functions of mutated genes, the most frequently involved genes were those involved in DNA methylation (38.27%), tyrosine kinase receptor signaling (32.1%), transcription regulation (28.4%), and RAS pathway (24.7%). Single gene mutation predominated in patient with cytogenetic abnormalities, while coexistence of 2 mutations have predominated in patient with normal cytogenetic findings. Stratified by cytogenetic findings, patients with single gene mutations (intermediate-risk group) had significantly higher complete remission (CR) rates than those with ≥2 gene mutations (unfavorable-risk group) (91.7% vs. 57.6% , 87.5% vs. 25.0%, P =0.0319, 0.0117, respectively). CONCLUSION Over 80% of AML patients were found to harbor at least one mutation. Their clinical phenotype and prognosis may be impacted by the synergy of MLL gene rearrangement and multiple mutations. For patients under the same risk stratification, the number of mutations is reversely correlated with the CR rate.
Cytogenetics ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia, Monocytic, Acute ; Leukemia, Myeloid, Acute ; Mutation ; Prognosis ; fms-Like Tyrosine Kinase 3

OBJECTIVE: To study the correlation of hematomorphology, bone marrow cytogenetics and clinical biochemical parameters with the prognosis of non-Hodgkin's lymphoma with bone marrow invasion. METHODS: Morphological analysis of bone marrow cells was performed by routine bone marrow puncture.Chromosome samples were prepared by short-term bone marrow culture. Karyotype analysis was carried out by R-banding in 28 patients. P53 gene was detected by fluorescence in situ hybridization (FISH). Serum lactate dehydrogenase (LDH) of all patients was determined and compared. RESULTS: In all patients, bone marrow morphology showed invasion of lymphoma. Chromosome analysis revealed abnormal karyotypes in 19 cases, which yielded an incidence of 67.85%. The proportion of lymphoma cells in bone marrow among those with an abnormal karyotype was much higher than those with a normal karyotype (60.2% vs. 33.5%, P<0.05). FISH assay showed that 9 (32.14%) patients had P53 gene deletion. And the deletion was much more common among those with an abnormal karyotype (42.11% vs. 11.11%, P<0.05). The serum LDH level in patients with an abnormal karyotype was significantly higher compared with whose with a normal karyotype (1464.37 U/L vs. 294.33 U/L, P<0.05). CONCLUSION Patients with abnormal karyotypes have a higher rate of P53 gene deletion, and their LDH level is significantly higher than those with a normal karyotype, which predicted a relatively poor prognosis.
Adult ; Bone Marrow ; Child ; Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Lymphoma, Non-Hodgkin

OBJECTIVE: To delineate the clinical and molecular characteristics of a patient with myeloid neoplasm and co-existence of t(7;11)(p15;p15) and t(5;12)(q33;p13) translocations. METHODS: Clinical data of the patient was collected. Conventional karyotyping, reverse transcriptase (RT)-PCR and next generation sequencing (NGS) were carried out to delineate its genetic features. RESULTS: The patient has featured recurrent rash, fatigue, loss of appetite and splenomegaly. Laboratory test suggested hyperleukocytosis of FAB-M2-subtype. Neither eosinophilia nor basophilia was presented. NUP98/HOXA9 and ETV6/PDGFRB fusion genes were detected by RT-PCR. NGS and DNA-PCR showed the co-existence of WT1 p.C423Y, KRAS p.G12D and DNMT3A p.R882C mutations. The patient achieved morphological remission after imatinib plus coventional chemotherapy (standard IAC regimen). However, the disease has relapsed shortly after. Treatment was switched to HHT-Ara-C-Acla regimen, no hematological response was observed. The ETV6/PDGFRB fusion gene was undetectable in bone marrow sample, though strong expression of NUP98/HOXA9 was detectable throughout the whole course. CONCLUSION Acute myeloid leukemia in association with the co-existence of NUP98/HOXA9 and ETV6/PDGFRB fusion genes have unique clinical and genetic features. Imatinib seems to have no impact on the overall survival in such cases.
Chromosomes, Human ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute ; Myeloproliferative Disorders ; Oncogene Proteins, Fusion ; Translocation, Genetic