RESUMO
Objective: To investigate the clinical and prognostic characteristics of newly diagnosed multiple myeloma (NDMM) patients with myelofibrosis (MF). Methods: The clinical data of 160 NDMM patients admitted to Henan Provincial People's Hospital from January 2012 to July 2022 were analyzed retrospectively. They were divided into MF group(n=74) and non-MF group(n=86) according to whether combined with MF. Patients in MF group were further splited into MF-1 group (n=47) and MF-2/3 group (n=27). All patients were treated with bortezomib and immunomodulatory-based combination therapy. The efficacy was evaluated after 4 courses, and the clinical features and prognosis between the two groups were compared. The deadline for follow-up was December 30, 2022 and the median follow-up period [M (Q1, Q3)] was 23.5 (14.4, 40.5) months. Kaplan-Meier method was used for survival analysis, and Cox regression model was used to analyze the influencing factors of survival. Results: Among 160 patients with NDMM, 91 were males and 69 were females, with a median age [M (Q1, Q3)] of 59 (54, 69) years. In MF group, the bone marrow immature plasma cell percentage, total plasma cell percentage were 9.6% (3.2%, 28.5%) and 36.4% (18.5%, 51.1%), respectively, which were higher than 6.0% (1.2%, 17.2%) and 24.0% (12.0%, 46.0%) of the non-MF group (both P<0.05). Hb level was 84.0(74.5, 100.5)g/L and PLT was (151.99±90.68) ×109/L in the MF group, which were lower than 96.0 (81.0, 112.0)g/L and (180.38±85.32) ×109/L of non-MF group (both P<0.05). But there were no significant differences in ISS stage, karyotypic and fluorescence in situ hybridization (FISH) high-risk genetic abnormalities between the two groups (all P>0.05). Objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) were not significantly different between the two groups (all P>0.05). The rate of 17p- was 25.9% (7/27) in MF-2/3 group, which was higher than 8.1% (7/86) of non-MF group (P=0.049). The median OS of the MF-2/3 group was 25.0 (95%CI: 23.6-26.4) months, which was shorter than that of the non-MF group (54.0 months, P=0.031). Multivariate Cox regression analysis showed that grade MF-2/3 was not a risk factor for OS in NDMM patients (HR=1.507, 95%CI: 0.624-3.993, P=0.425). Conclusions: The ratio of bone marrow immature plasma cells and total plasma cells in NDMM patients with MF are higher than that in patients without MF, and the Hb and PLT are lower than that in patients without MF. NDMM patients with grade 2/3 MF have shorter survival than those without MF.
Assuntos
Mieloma Múltiplo , Mielofibrose Primária , Masculino , Feminino , Humanos , Prognóstico , Mieloma Múltiplo/diagnóstico , Hibridização in Situ Fluorescente , Estudos RetrospectivosRESUMO
Objective: To explore the characteristics, clinical features and prognostic effects of NOTCH1/FBXW7 gene mutations in T-cell acute lymphoblastic leukemia (T-ALL) patients. Methods: The clinical data of 61 T-ALL patients who underwent second-generation gene sequencing in Henan Provincial People's Hospital from March 2016 to March 2021 were retrospectively analyzed. There were 46 males and 15 females, with a median age [M (Q1, Q3)] of 18 (11, 30) years. The relationship between NOTCH1/FBXW7 gene mutation characteristics, clinical and laboratory parameters and their impact on event free survival (EFS) and overall survival (OS) were analyzed. Results: NOTCH1 gene mutations were found in 34 cases (55.7%, 34/61), including 22 cases of heterodimer domain (HD) mutations (64.7%), 7 cases of proline/glutamate/serine/threonine (PEST) mutations (20.6%), and 5 cases of both HD and PEST mutations (14.7%). FBXW7 gene mutations were detected in 9 cases (14.8%, 9/61), of which 5 cases had both NOTCH1 and FBXW7 gene mutations. Twenty-three (37.7%, 23/61) cases were wild type. The median white blood cell count of patients in NOTCH1/FBXW7 gene mutations group and wild-type group was 76.4×109/L (8.3×109/L, 149.2×109/L), 54.1×109/L (5.3×109/L, 156.6×109/L), respectively. Moreover, the hemoglobin was (89.1±27.1) g/L and (99.5±23.1) g/L, respectively, and the median proportion of bone marrow primordial cells was 84.5% (69.0%, 91.3%) and 60.0%(35.0%, 80.0%), respectively. The gene expression rate of SIL-TAL1, Hox11 and Hox11L2 was 7.9% (3/38) vs 17.4% (4/23), 18.4% (7/38) vs 4.3% (1/23), 5.3% (2/38) vs 13.0% (3/23), respectively (all P>0.05). However, the median platelet level in the NOTCH1/FBXW7 gene mutations group was 60.5×109/L (36.8×109/L, 100.3×109/L), which was lower than that in the wild-type group [116.0×109/L (63.0×109/L, 178.0×109/L)] (P=0.018). The median number of gene mutations in the group with NOTCH1/FBXW7 gene mutations group was 2.5 (1.8, 4.0), which was more than that in the group without NOTCH1/FBXW7 gene mutations group [0 (0, 1.0)] (P<0.001). The median EFS and OS of adult NOTCH1/FBXW7 gene mutations group were 28.0 (95%CI: 7.3-48.7) months and 30.0 (95%CI: 8.9-51.1) months, respectively, which were better than those of adult wild-type group [4.5 (95%CI: 0-11.6) months and 9.0 (95%CI: 0-19.1) months] (P=0.008 and 0.014).The median EFS and OS of children NOTCH1/FBXW7 gene mutations group were 12.0 (95%CI: 10.4-13.6) months and 19.0 (95%CI: 13.6-24.4) months, respectively, and those of wild-type group were 10.0 (95%CI: 8.9-11.1) months and 21.0 (95%CI: 0-51.4) months, respectively (P=0.673 and 0.434). Conclusions: The mutation rate of NOTCH1/FBXW7 gene is higher in T-ALL patients. Patients with NOTCH1/FBXW7 gene mutations group have lower platelet count and better EFS and OS. NOTCH1/FBXW7 gene mutation may be used as a hierarchical basis for individualized treatment of adult T-ALL patients.
Assuntos
Proteína 7 com Repetições F-Box-WD , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptor Notch1 , Adulto , Proteínas de Ciclo Celular/genética , Criança , Proteína 7 com Repetições F-Box-WD/genética , Feminino , Humanos , Masculino , Mutação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Prognóstico , Receptor Notch1/genética , Estudos Retrospectivos , Linfócitos T , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/uso terapêuticoRESUMO
Objective: To investigate the effects of additional chromosomal abnormalities (ACA) in Philadelphia chromosome-positive (Ph(+)) cells on biological characteristics, therapy efficacy, and prognosis of patients with primary chronic myeloid leukemia (CML) -chronic phase (CP) and those who developed CML-accelerated phase/blast phase (AP/BP) during therapy. Methods: The clinical data of 410 patients with Ph(+) CML, including 348 patients with primary CML-CP and 62 patients who progressed to CML-AP/BP during treatment, who were admitted to Henan People's Hospital from January 2013 to June 2020 were retrospectively analyzed to categorize into high-risk, non-high-risk, and non-ACA groups according to the ELN2020 criteria. The effects of high- and non-high-risk ACA on biological characteristics, therapy efficacy, and prognosis were compared. Results: â Among the 348 patients with primary CML-CP, 20 patients (5.75% ) had ACA, including 3 and 17 patients with high-risk and non-high-risk ACA, respectively, whereas the remaining 328 patients did not have ACA. There were no significant differences in baseline clinical characteristics between those with and without ACA (P>0.05 for all) . The rates of complete hematological response, complete cytogenetic response, major molecular remission, and 5-year overall survival (OS) were not significantly different between the non-high-risk ACA and non-ACA groups (P>0.05 for all) ; however, the 5-year progression-free survival of the non-high-risk ACA group (42.0% ) was significantly lower than that of the non-ACA group (74.5% ) (χ(2)=4.766, P=0.029) .â¡Of the 62 patients who progressed to CML-AP/BP during treatment, 41 patients (66.13% ) had ACA, including 28 and 13 patients with high-risk and non-high-risk ACA, respectively, whereas the remaining 21 patients did not have ACA. Platelet counts of the high-risk ACA group (42.5×10(9)/L) were lower than those of the non-high-risk (141×10(9)/L) and non-ACA groups (109×10(9)/L) (χ(2)=4.968, P=0.083) . There was no significant difference in the incidence of point mutations in ABL kinase among the three groups (P=0.652) . The complete cytogenetic response of the high-risk ACA group (5.3% ) was significantly lower than that of the non-ACA group (46.7% ) (χ(2)=5.851, P=0.016) . The 5-year OS of the high-risk ACA group was lower than that of the non-ACA group (46.2% vs 77.8% , χ(2)=3.878, P=0.049) . Subgroup analysis revealed that the 5-year OS rate of the high-risk group â ¡, which included -7/7q-, i (17q) , and complex karyotype comprising ≥2 high-risk ACA, was significantly lower than that of the non-ACA group (28.6% vs 77.8% , χ(2)=8.035, P=0.005) whereas the 5-year OS rate was not significantly different between high-risk group â , which included +8,+Ph, and complex ACA with +8/+Ph, and the non-ACA group (54.5% vs 77.8% , χ(2) =1.514, P=0.219) . Conclusion: Due to different disease stages and ACA/Ph(+) types, treatment response and prognosis vary among patients with CML harboring ACA/Ph(+). The emergence of high-risk ACA during therapy suggests worse therapy efficacy and prognosis. Strict and standardized cytogenetic monitoring is critical for early detection, precise diagnosis, and treatment of these patients.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Crise Blástica , Aberrações Cromossômicas , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To analyze the effect of triple-induction regimen including all-trans retinoic acid(ATRA), arsenic trioxide(ATO) plus anthracyclines and double-induction regimen including ATRA and ATO for adults with non-high-risk acute promyelocytic leukemia(APL). Methods: The clinical data of adult patients with non-high-risk APL who were first diagnosed and admitted to the Henan Provincial People's Hospital from January 2009 to December 2019 were retrospectively analyzed. All patients were divided into triple-induction group and double-induction group according to the treatment. The general data of patients, blood routine, coagulation function changes and blood transfusions during the induction period were collected, and the complete remission rate, early mortality and prognosis of two groups were analyzed. Results: A total of 164 patients were enrolled, including 86 males and 78 females, and the M(Q1,Q3) of their age was 41(18, 70) years. Among them, 75 were in triple-induction group and 89 in double-induction group. The white blood cell(WBC) counts of triple-induction group on day 7th and 14th after induction were (9.49±6.10)×109/L and (5.43±3.97)×109/L, while those in double-induction group were (15.17±17.06)×109/L and (13.37±12.59)×109/L, the differences were statistically significant (both P<0.05). In addition, the peak of WBC in the triple-induction group was lower than that in the double-induction group [13.8(6.3,89.7)×109/L vs 19.2(3.8,112.8)×109/L, P=0.019]. On day 7th after induction, the platelet(PLT) counts in the triple-induction group was lower than that in the double-induction group [27(11,147)×109/L vs 45(8, 183)×109/L, P=0.014]. However, the difference was not statistically significant in PLT counts between the two groups on day 14th, 21st and 28th, or in PLT transfusions during induction (all P>0.05). After treatment, it was observed only in a few patients of two groups that the prothrombin time(PT) elongation ≥3 s and/or activated partial thromboplastin time(APTT) elongation ≥10 s, and the difference was not statistically significant (all P>0.05). The incidence of induced differentiation syndrome in the triple-induction group was lower than that in the double-induction group (2.7% vs 12.4%, P=0.022) The early mortality rate was lower than that in the double-induction group (1.3% vs 5.6%), but the difference was not statistically significant (P>0.05). There were no statistically significant differences in the early complete remission rate, genetic remission rate, molecular remission rate, relapse rate, overall survival (OS) rate and disease-free survival (DFS) rate between the two groups. Conclusion: For adults with non-high-risk APL, the triple-induction therapy can reduce the counts and peaks of WBC, and reduce the incidence of induced differentiation syndrome.
Assuntos
Arsenicais , Leucemia Promielocítica Aguda , Adulto , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Arsenicais/uso terapêutico , Feminino , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Masculino , Óxidos/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Tretinoína/uso terapêuticoRESUMO
Objective: This study aims to investigate the characteristics of gene mutation and clinical prognosis in de novo acute myeloid leukemia (AML) patients with myelofibrosis (MF) . Methods: From January 1, 2016, to February 1, 2020, 103 newly diagnosed AML patients in Henan Provincial People's Hospital who simultaneously underwent bone marrow biopsy examination were included. They were divided into the AML-MF group (MF grades 1-3) and the AML without MF group (MF grade 0) , and the clinical features, gene alterations, chemotherapy efficacy, and prognosis were compared between the two groups retrospectively. Results: â MF was confirmed in 44.7% of AML patients (46/103) , of which 84.8% (39/46) were MF-1 and 15.2% (7/46) were MF-2/3, while MF was not confirmed in 55.3% (57/103) of AML patients. The median of WBC in the AML-MF group was significantly higher than in the AML without MF group [11.205 (0.69-191.82) ×10(9)/L vs 4.64 (0.18-95.10) ×10(9)/L, P=0.024]. More patients in the AML-MF group had nucleated erythrocytes in the peripheral blood (43.5% vs 24.6% , χ(2)=4.119, P=0.042) . All four AML-M(0) patients were in the AML-MF group, while AML without MF group had a higher proportion of AML-M(2) (P=0.014) . â¡FLT3-ITD and NPM1 mutations were more frequent in the AML-MF group (P=0.021 and 0.039) , while CEBPA mutation was more frequent in the AML without MF group (P=0.029) . â¢The CR rate in the AML-MF group was significantly lower than in the AML without MF group (69.7% vs 93.2% ) (χ(2) =7.412, P=0.006) . Multivariate analysis showed that MF, especially the grade of fibrosis, was an independent risk factor for CR in de novo AML. â£The 3-year OS of patients in the AML-MF group was significantly lower than in the AML without MF group (20.5% vs 72.2% , χ(2)=4.032, P=0.045) . Subgroup analysis showed that OS and PFS of AML-MF1 and AML-MF 2/3 groups were also significantly worse than those of the AML without MF group (P=0.001) and MF, especially MF ≥2, was an independent marker for inferior OS and PFS in de novo AML (P=0.021 and 0.044) . Conclusion: AML-MF has unique laboratory and clinical characteristics. MF is an independent risk factor for CR, OS, and PFS in AML. Evaluation of MF is very significant for therapy efficacy and prognosis judgment in de novo AML.
Assuntos
Leucemia Mieloide Aguda , Mielofibrose Primária , Humanos , Leucemia Mieloide Aguda/genética , Mutação , Nucleofosmina , Mielofibrose Primária/genética , Prognóstico , Estudos Retrospectivos , Tirosina Quinase 3 Semelhante a fmsRESUMO
Objective: To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide ß(ß-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD). Methods: From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5bãß-CTXãPINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed. Results: After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, ß-CTX and vitamin D3 were decreased significantly (P<0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference (t=-1.871, P=0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference (t=-8.272, P<0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ(2)=0.569, P=0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ(2)=6.260, P=0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L,t=5.762, P<0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) µg/L vs (15.6±5.5) µg/L, t=-2.478, P=0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ(2)=4.076, P=0.044). There was no significant difference in the serum concentration of TRACP-5b and ß-CTX between two groups. Conclusion: After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, ß-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.
Assuntos
Doenças Ósseas , Mieloma Múltiplo , Fosfatase Ácida , Biomarcadores , Humanos , Inibidores de Proteassoma , Fosfatase Ácida Resistente a TartaratoRESUMO
Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F â § inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
Assuntos
Fator VIII/uso terapêutico , Hemofilia A , Criança , Hemartrose , Hemofilia A/tratamento farmacológico , Hemorragia , Humanos , Estudos RetrospectivosRESUMO
Objective: To analyze the percentage of myeloperoxidase (MPO)-positive acute myeloid leukemia (AML) blast cells, and to explore the correlation of MPO expression with the clinical features, gene alterations, therapeutic response and prognosis of AML. Methods: The expressions of MPO in BM blasts cells of 233 newly diagnosed AML were retrospectived analyzed, they were divided into two groups using the percentage of MPO-positive blast [low (≤70%) and high (>70%)], clinical features, gene alterations, chemotherapy efficacy and prognosis were compared between the two groups. Results: â Of the 233 patients, 121(51.9%) were in the low MPO group, and the rest 112(48.1%) in the high MPO group. Favorable-risk group according NCCN guidelines of AML was always MPO-high (χ(2)=32.773, P<0.001), while MPO-low was closely related to poor-risk (χ(2)=7.078, P=0.008); â¡DNMT3A mutation (χ(2)=6.905, P=0.009), spliceosome genes mutation (SF3B1/SRSF2/U2AF1) (χ(2)=5.246, P=0.022), RUNX1 mutation (χ(2)=4.577, P=0.032), ASXL1 mutation (χ(2)=7.951, P=0.005) and TP53 mutation (P=0.004) were more likely to be seen in the low MPO group, while C-KIT mutation (χ(2)=8.936, P=0.003) and CEBPA mutation (χ(2)=12.340, P<0.001) were more frequent in the high MPO group, especially CEBPA double mutation; â¢The rates of first complete remission in the low MPO group were significantly lower than that in the high MPO group (38.8% vs 68.1%, χ(2)=15.197, P<0.001). Multivariate analysis showed that low MPO positivity significantly affected the CR(1) unfavourably. â£The overall survival (OS) and the progression-free survival (PFS) were significantly worse in the low MPO group (18.0% vs 89.4% for OS, and 11.5% vs 56.7% for PFS, P<0.001). Multivariate analysis disclosed that the low number of MPO was significantly unfavourable prognostic factor. â¤The low MPO group still showed a worse survival even when restricted to the patients with normal karyotype, the OS and the PFS were 31.1% and 18.8% respectively. Conclusions: AML with different MPO expression percentage had a unique gene mutation spectrum. Low expression of MPO was an independent risk factor for CR(1), OS and PFS in AML patients, which may be a simple and highly significant factor for AML patients when evaluating the therapeutic efficacy and prognosis.
Assuntos
Leucemia Mieloide Aguda , Humanos , Mutação , Peroxidase , Prognóstico , Indução de RemissãoRESUMO
Objective: To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) . Methods: The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People's Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored. Results: â Among the 137 patients, the positive ratios of CD34, CD2, CD56 expressions and mutation rate of FLT3-ITD were 26.3%, 25.5%, 10.2% and 17.5%, respectively. The morbidities of positive CD34, CD2, CD56 expressions and FLT3-ITD mutation in the high-risk group were 43.2%, 47.7%, 18.2% and 27.3% respectively, while those in the low-/intermediate-risk groups were 18.3%, 15.1%, 6.5% and 12.9%, respectively (P<0.05) . â¡At a median follow-up of 41 months, the total CR rate of the 137 adults APL patients was 96.9%, early mortality 6.6% and relapse rate 7.3% respectively. And RR of positive CD34 or CD2 expression patients was higher than negative CD34/CD2 expression ones (18.8% vs 3.3%, χ(2)=8.462, P=0.004; 16.1% vs 4.3%, χ(2)=4.382, P=0.028, respectively) . In addition, the early mortality of patients with positive CD56 expression or FLT3-ITD mutation was extremely higher than in negative ones (21.4% vs 4.9%, χ(2)=5.610, P=0.018; 16.7% vs 4.4%, χ(2)=4.833, P=0.028, respectively) . â¢The whole OS and DFS were 88.3% and 84.7%, respectively. Wherein, OS and DFS in patients with CD34(+), CD56(+) or FLT3-ITD mutation were worse (P<0.05) . Conclusions: Positive CD34, CD2, CD56 expression and FLT3-ITD mutation were latent poor prognostic factors in adults with APL.