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1.
Br J Haematol ; 205(3): 924-931, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38706448

RESUMO

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.


Assuntos
Leucemia Mieloide Aguda , Nucleofosmina , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Estudos Retrospectivos , Idoso , Adulto , Grânulos Citoplasmáticos/patologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Tirosina Quinase 3 Semelhante a fms/genética , Mutação , Proteínas Nucleares/genética , Idoso de 80 Anos ou mais , Adolescente , Adulto Jovem , Fibrinogênio/análise , Hemorragia/etiologia
2.
Br J Haematol ; 204(3): 861-870, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37939390

RESUMO

Gilteritinib, a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor, was approved for relapsed/refractory (R/R) FLT3-mutated acute myeloid leukaemia (AML) patients but still showed limited efficacy. Here, we retrospectively analysed the efficacy and safety of different gilteritinib-based combination therapies (gilteritinib plus hypomethylating agent and venetoclax, G + HMA + VEN; gilteritinib plus HMA, G + HMA; gilteritinib plus venetoclax, G + VEN) in 33 R/R FLT3-mutated AML patients. The composite complete response (CRc) and modified CRc (mCRc) rates were 66.7% (12/18) and 88.9% (16/18) in patients received G + HMA + VEN, which was higher compared with that in G + HMA (CRc: 18.2%, 2/11; mCRc: 45.5%, 5/11) or G + VEN (CRc: 50.0%, 2/4; mCRc: 50.0%, 2/4). The median overall survival (OS) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 160.0 days and 231.0 days. The median duration of remission (DOR) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 82.0 days and 77.0 days. Four patients in the G + HMA + VEN group received alloHSCT after remission exhibited prolonged median DOR. The most common grade 3/4 adverse events were cytopenia, febrile neutropenia and pulmonary infection; there were no differences among the three groups. In conclusion, our data demonstrated promising response of G + HMA + VEN combination therapy in R/R FLT3-mutated AML, and it may be considered an effective therapy bridge to transplantation.


Assuntos
Compostos de Anilina , Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Mieloide Aguda , Pirazinas , Sulfonamidas , Tirosina Quinase 3 Semelhante a fms , Adulto , Humanos , Estudos Retrospectivos
3.
Br J Haematol ; 204(6): 2342-2350, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38400570

RESUMO

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Etoposídeo , Filgrastim , Mobilização de Células-Tronco Hematopoéticas , Linfoma , Mieloma Múltiplo , Polietilenoglicóis , Humanos , Filgrastim/administração & dosagem , Filgrastim/uso terapêutico , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Feminino , Masculino , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Adulto , Linfoma/tratamento farmacológico , Linfoma/terapia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Estudos Prospectivos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/métodos , Adulto Jovem , Adolescente
4.
BMC Cancer ; 24(1): 955, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103751

RESUMO

BACKGROUND: For myeloid neoplasms with t(7;11)(p15;p15) translocation, the prognosis is quite dismal. Because these tumors are rare, most occurrences are reported as single cases. Clinical results and optimal treatment approaches remain elusive. This study endeavors to elucidate the clinical implications and prognosis of this cytogenetic aberration. METHODS: This study retrospectively analyzed 23 cases of myeloid neoplasm with t(7;11)(p15;p15). Clinicopathological characteristics, genetic alterations, and outcomes were evaluated, and the Kaplan-Meier method was employed to construct survival curves. RESULTS: Of these, nine cases were newly diagnosed acute myeloid leukemia (ND AML), seven presented with relapsed refractory AML (R/R AML), four had myelodysplastic syndrome (MDS), two had secondary AML, and one exhibited a mixed germinoma associated with MDS. Patients with t(7;11)(p15;p15) in AML were primarily younger females who preferred subtype M2. Interestingly, these patients had decreased hemoglobin and red blood cell counts, along with markedly elevated levels of lactic dehydrogenase and interleukin-6, and exhibited the expression of CD117. R/R AML patients exhibited a higher likelihood of additional chromosome abnormalities (ACAs) besides t(7;11). WT1 and FLT3-ITD were the most commonly found mutated genes, and 10 of those instances showed evidence of the NUP98::HOXA9 fusion gene. The composite complete remission rate was 66.7% (12/18), while the cumulative graft survival rate was 100% (4/4). However, the survival outcomes were dismal. Interestingly, the median overall survival for R/R AML patients was 4.0 months (95% CI: 1.7-6.4). Additionally, the type of AML diagnosis or the presence of ACAs or molecular prognostic stratification did not significantly influence clinical outcomes (p = 0.066, p = 0.585, p = 0.570, respectively). CONCLUSION: Myeloid leukemia with t(7;11) exhibits unique clinical features, cytogenetic properties, and molecular genetic characteristics. These survival outcomes were dismal. R/R AML patients have a limited lifespan. For myeloid patients with t(7;11), targeted therapy or transplantation may be an effective course of treatment.


Assuntos
Cromossomos Humanos Par 11 , Translocação Genética , Humanos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Prognóstico , Cromossomos Humanos Par 11/genética , Adulto Jovem , Idoso , Adolescente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/patologia , Cromossomos Humanos Par 7/genética , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia
5.
Hematol Oncol ; 42(2): e3260, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38415873

RESUMO

Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy (DAV) has shown safety and efficacy in eligible patients with newly diagnosed acute myeloid leukemia (AML). However, there are no direct comparisons between DAV and 3 + 7 daunorubicin and cytarabine chemotherapy (DA) alone. We performed a propensity score-matched analysis to compare the outcomes of DAV group with historical DA group and identify the clinical and molecular characteristics of patients who might benefit from the DAV regimen. The DAV group had a higher Complete remission (CR) rate than the DA group (90% vs. 55%, p = 0.008). 25 (96%) patients in the DAV group had a higher MRD-negative CRc rate compared with 13 (62%) patients in the DA group (p = 0.006). After a median follow-up duration of 19.15 (IQR 17.13-21.67) months, the DAV group had an improved overall survival (p = 0.001) and event-free survival (p = 0.069), but not disease-free survival (p = 0.136). Collectively, DAV regimen induced high CR rates and deep MRD-negative CRc rates after one cycle of induction therapy, as well as prolonged the overall survival, in young adult patients with AML who were eligible for intensive chemotherapy. The addition of venetoclax to intensive chemotherapy should be considered in the future to achieve better survival advantages in eligible AML patients.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Mieloide Aguda , Sulfonamidas , Adulto Jovem , Humanos , Pontuação de Propensão , Leucemia Mieloide Aguda/tratamento farmacológico , Daunorrubicina , Citarabina , Resposta Patológica Completa
6.
Ann Hematol ; 103(9): 3315-3334, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39017945

RESUMO

Diffuse large B-cell lymphoma (DLBCL), with approximately 150,000 new cases worldwide each year, represent nearly 30% of all cases of non-Hodgkin lymphoma (NHL) and are phenotypically and genetically heterogeneous. A gene-expression profile (GEP) has identified at least three major subtypes of DLBCL, each of which has distinct clinical, biological, and genetic features: activated B-cell (ABC)-like DLBCL, germinal-center B-cell (GCB)-like DLBCL, and unclassified. Different origins are associated with different responses to chemotherapy and targeted agents. Despite DLBCL being a highly heterogeneous disease, more than 60% of patients with DLBCL can be cured after using rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) to inhibit the growth of cancer cells while targeting the CD20 receptor. In recent decades, the improvement of diagnostic levels has led to a refinement classification of DLBCL and the development of new therapeutic approaches. The objective of this review was to summarize the latest studies examining genetic lesions and therapies for DLBCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Linfoma Difuso de Grandes Células B , Rituximab , Vincristina , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Rituximab/uso terapêutico , Ciclofosfamida/uso terapêutico , Vincristina/uso terapêutico , Prednisona/uso terapêutico , Doxorrubicina/uso terapêutico
7.
Ann Hematol ; 103(6): 2165-2168, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38584216

RESUMO

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN.


Assuntos
Bussulfano , Células Dendríticas , Transplante de Células-Tronco Hematopoéticas , Tiotepa , Condicionamento Pré-Transplante , Vidarabina , Humanos , Vidarabina/análogos & derivados , Vidarabina/administração & dosagem , Vidarabina/uso terapêutico , Condicionamento Pré-Transplante/métodos , Células Dendríticas/patologia , Tiotepa/administração & dosagem , Tiotepa/uso terapêutico , Masculino , Bussulfano/administração & dosagem , Bussulfano/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/patologia , Feminino , Transplante Homólogo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aloenxertos
8.
Am J Hematol ; 99(9): 1768-1777, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38884175

RESUMO

Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open-label, multicenter, phase 3 trial evaluating the non-inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor-naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co-primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT-Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non-inferior to eculizumab in the co-primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, -2.8 [-15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, -3.9 [-14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [-11.4, 16.3]). A clinically meaningful improvement in FACIT-Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit-risk profile of crovalimab.


Assuntos
Anticorpos Monoclonais Humanizados , Inativadores do Complemento , Hemoglobinúria Paroxística , Humanos , Hemoglobinúria Paroxística/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Inativadores do Complemento/uso terapêutico , Inativadores do Complemento/efeitos adversos , Hemólise/efeitos dos fármacos , Complemento C5/antagonistas & inibidores , Idoso
9.
BMC Infect Dis ; 24(1): 1141, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39394593

RESUMO

PURPOSE: The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. METHODS: Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan-Meier product limit approach was employed. RESULTS: In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294-9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361-5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158-0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167-0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P < 0.001). CONCLUSIONS: In conclusion, the study determined that HM patients with COVID-19 and increased C-reactive protein levels had a higher likelihood of severe health outcomes. Persistent infection tended to be more prevalent in those with vaccine dosages (< 2 doses), lower IgG levels, and higher interleukin-6 levels.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Neoplasias Hematológicas , Imunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/sangue , COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Estudos Retrospectivos , SARS-CoV-2/imunologia , Imunoglobulina G/sangue , Adulto , Idoso , Anticorpos Antivirais/sangue , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinação
10.
Cancer ; 129(10): 1523-1536, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36882308

RESUMO

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) as postremission treatment is recommended for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) in current guidelines. However, comparisons of later generation tyrosine kinase inhibitors (TKIs) plus chemotherapy with allo-HSCT have yielded similar outcomes. This meta-analysis was performed to evaluate allo-HSCT in first complete remission (CR1) versus chemotherapy for adult Ph+ ALL in the TKI era. METHODS: Pooled assessment of the hematologic and molecular complete response rates was performed after 3-month TKI treatment. Hazard ratios (HRs) were determined for disease-free survival (DFS) and overall survival (OS) benefit with allo-HSCT. The effect of measurable residual disease status on survival benefit was also analyzed. RESULTS: Thirty-nine retrospective and prospective single-arm cohort studies involving 5054 patients were included. Combined HRs indicated that in the general population, allo-HSCT favorably influenced DFS and OS. Achieving complete molecular remission (CMR) within 3 months after starting induction was a favorable survival prognostic factor regardless of whether the patient had undergone allo-HSCT. Among the patients with CMR, survival rates in the nontransplant subgroup were comparable with those in the transplant subgroup, with the estimated 5-year OS of 64% versus 58% and 5-year DFS of 58% versus 51%, respectively. The use of next-generation TKIs results in a higher proportion of patients achieving CMR (ponatinib 82% vs. imatinib 53%), while improving survival in nontransplant patients. CONCLUSION: Our novel findings suggest that combination chemotherapy plus TKIs leads to a comparable survival benefit as with allo-HSCT for MRD-negative (CMR) patients. This study provides novel evidence for allo-HSCT indications for Ph+ ALL in CR1 in the TKI era.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adulto , Cromossomo Filadélfia , Estudos Retrospectivos , Estudos Prospectivos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Neoplasia Residual , Inibidores de Proteínas Quinases/uso terapêutico
11.
Br J Cancer ; 128(4): 691-701, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36482192

RESUMO

BACKGROUND: Decitabine (DAC) is used as the first-line therapy in patients with higher-risk myelodysplastic syndromes (HR-MDS) and elderly acute myeloid leukaemia (AML) patients unsuitable for intensive chemotherapy. However, the clinical outcomes of patients treated with DAC as a monotherapy are far from satisfactory. Adding all-trans retinoic acid (ATRA) to DAC reportedly benefitted MDS and elderly AML patients. However, the underlying mechanisms remain unclear and need further explorations from laboratory experiments. METHODS: We used MDS and AML cell lines and primary cells to evaluate the combined effects of DAC and ATRA as well as the underlying mechanisms. We used the MOLM-13-luciferase murine xenograft model to verify the enhanced cytotoxic effect of the drug combination. RESULTS: The combination treatment reduced the viability of MDS/AML cells in vitro, delayed leukaemia progress, and extended survival in murine xenograft models compared to non- and mono-drug treated models. DAC application as a single agent induced Nrf2 activation and downstream antioxidative response, and restrained reactive oxygen species (ROS) generation, thus leading to DAC resistance. The addition of ATRA blocked Nrf2 activation by activating the RARα-Nrf2 complex, leading to ROS accumulation and ROS-dependent cytotoxicity. CONCLUSIONS: These results demonstrate that combining DAC and ATRA has potential for the clinical treatment of HR-MDS/AML and merits further exploration.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Animais , Camundongos , Idoso , Decitabina/farmacologia , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio , Antineoplásicos/uso terapêutico , Síndromes Mielodisplásicas/induzido quimicamente , Síndromes Mielodisplásicas/tratamento farmacológico , Tretinoína/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Azacitidina
12.
Br J Haematol ; 202(4): 745-748, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37230766

RESUMO

There have been reports of haematological cancer patients achieving spontaneous remission after being infected with the influenza A or SARS-COV-2 virus. Here, we present the first case of long-term complete remission (CR) induced by influenza A (IAV, H1N1 subtype) in a refractory AML patient and have functionally validated this finding in two different animal disease models. We observed a significant increase in the proportion of helper T cells in the patient after IAV infection. The levels of cytokines, including IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α, were higher in IAV-infected patients compared with control groups. These findings indicate that the anti-tumour effects induced by IAV are closely related to the modification of the immune response. Our study provides new evidence of the anti-tumour effects of IAV from a clinical practice perspective.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana , Leucemia Mieloide Aguda , Animais , Humanos , SARS-CoV-2
13.
Br J Haematol ; 202(1): 111-115, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37038274

RESUMO

As reported, SETD2 is recurrently mutated in acute myeloid leukaemia (AML), but knowledge about the specifics is limited. We enrolled 530 consecutive newly diagnosed AML patients in our study, and we analysed the distribution pattern and prognostic role of SETD2 mutation in AML. SETD2 mutation was found to affect 6.3% of AML patients, and it frequently co-occurred with IDH2, NRAS and CEBPA mutations. SETD2-mutated patients saw excellent therapeutic responses but failed to gain better survival time than other patients. This could be because of the high recurrence and mortality in SETD2-mutated patients who have additional mutations, such as NRAS mutation.


Assuntos
Leucemia Mieloide Aguda , Nucleofosmina , Humanos , Prognóstico , Mutação , Leucemia Mieloide Aguda/terapia
14.
Br J Haematol ; 202(6): 1119-1126, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37434414

RESUMO

To reducing chemotherapy-related toxicity, the chemo-free regimens become a new trend of Ph + ALL treatment. Therefore, we conducted a phase 2 trial of dasatinib plus prednisone, as induction (Course I) and early consolidation (Courses II and III) treating newly diagnosed Ph + ALL. The trial was registered at www.chictr.org.cn, ChiCTR2000038053. Forty-one patients were enrolled from 15 hospitals. The complete remission (CR) was 95% (39/41), including two elderly induction deaths. By the end of Course III, 25.6% (10/39) of patients achieved a complete molecular response. With a median follow-up of 15.4 months, 2-year disease-free survival (DFS) were 100% and 33% for patients who receiving haematopoietic stem cell transplantation (HSCT) at CR1 and receiving chemotherapy alone respectively. When censored at time of HSCT, 2-year DFS were 51% and 45% for young and elderly patients (p = 0.987). 2-year overall survival were 45%, 86% and 100% for patients without HSCT, receiving HSCT after relapse and receiving HSCT at CR1 respectively. A total of 12 patients had marrow recurrences and one had CNS relapse, with 38% occurred early (between Courses I and III). IKZF1 gene deletion was shown to be associated with relapse (p = 0.019). This chemo-free induction and early consolidation regimen was efficacious and well-tolerated in de novo Ph + ALL. Allogeneic HSCT conferred definite survival advantage after chemo-free induction.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adulto , Idoso , Dasatinibe/efeitos adversos , Prednisona/efeitos adversos , Cromossomo Filadélfia , Recidiva Local de Neoplasia/tratamento farmacológico , Intervalo Livre de Doença , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Indução de Remissão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
15.
Hematol Oncol ; 41(1): 159-166, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36316121

RESUMO

Single gene mutations in the RAS pathway are uncommon and of unknown significance in myelodysplastic syndrome (MDS) patients, RAS pathway-related gene mutations (RASwaymut ) as a whole may be significant and require further elucidation. The clinical and molecular data of 370 MDS patients who were newly diagnosed between 1 November 2016 and 31 August 2020 in our hospital were collected and retrospectively reviewed. RASwaymut were detected in 57 (15.41%) patients. Higher median percentage of marrow blasts (2% vs. 1%, P = 0.00), more co-mutated genes (4, interquartile range [IQR]: 2-5. vs. 2, IQR:1-4, P = 0.00), more higher risk patients according to international prognostic scoring system-revised (IPSS-R) (80.70% vs. 59.11%, P = 0.002) as well as higher acute myeloid leukemia transformation rate (35.09% vs. 14.38%, P = 0.02) were observed in patients with RASwaymut when compared to those with wild type RAS pathway-related genes (RASwaywt ). The most frequent co-mutated genes were ASXL1 (28.6%), TET2 (23.2%), U2AF1, RUNX1, TP53 (14.3%); DNMT3A (12.5%), among which ASXL1 mutation rate were significantly higher than those with RASwaywt (p < 0.05). RASwaymut had no significant effect on response to disease-modifying treatment in MDS patients. However, Overall survivals (OS) of RASwaymut patients were significantly shorter than those with RASwaywt (16.05 m. vs. 92.3 m, P = 0.00), especially in patients with marrow blasts less than 5% (P = 0.002), normal karyotype (P = 0.01) and lower risk (P = 0.00). While multivariate prognostic analysis showed that RASwaymut co-mutated with TET2 was an independent poor prognostic factor for all MDS patients (P = 0.00, hazrad ratio [HR] = 4.77 with 95% confidence interval [CI]: 2.4-9.51) and RASwaymut patients (P = 0.02, HR 2.76, 95% CI 1.21-6.29). In conclusion, RASwaymut was associated with higher IPSS-R risk, higher incidence of leukemic transformation thus shorter OS in MDS patients, it could be viewed as a whole to predict poor prognosis. Co-mutation with TET2 may promote disease progression and was an independent poor prognostic factor in MDS patients.


Assuntos
Relevância Clínica , Síndromes Mielodisplásicas , Humanos , Estudos Retrospectivos , Mutação , Prognóstico , Síndromes Mielodisplásicas/genética
16.
Hematol Oncol ; 41(3): 546-554, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36516239

RESUMO

The treatment of patients with refractory and/or relapsed (R/R) high-risk myelodysplastic syndrome (HR-MDS) remains a daunting clinical challenge. Venetoclax is a selective BCL-2 inhibitor, which combined with hypomethylating agents (HMAs), increased responses and prolonged survival in unfit and previously untreated acute myeloid leukemia. We performed a retrospective study of patients with R/R HR-MDS receiving combination azacytidine (AZA) plus 15-days duration of venetoclax (VEN-15d) in order to determine their efficacy and toxicity in this context. We showed that the overall response rate was 57.2% (20/35) and the median over survival was 14 months in R/R MDS. The most common treatment-emergent adverse events were peripheral blood cytopenias and infectious complications. Our retrospective study showed that the real-world experience of treating R/R MDS with AZA plus VEN-15d highlights an encouraging response rate with myelosuppression being the major toxicity. Of note, VEN-15d with AZA may salvage patients failing to respond optimally to HMAs and reduce the disease-burden for subsequent allogeneic stem cell transplantation in our analysis. These data of combination AZA plus VEN-15d in R/R MDS warrant further prospective evaluation in clinical trials.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Azacitidina/efeitos adversos , Estudos Retrospectivos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/terapia
17.
Ann Hematol ; 102(11): 3153-3165, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37684379

RESUMO

Diffuse Large B Cell Lymphoma (DLBCL) is the most common form of blood cancer. Among the subtypes, the activated B-cell (ABC) subtype is typically more aggressive and associated with worse outcomes. However, the underlying mechanisms are not fully understood. In this study, we performed microarray analysis to identify potential ABC-DLBCL-associated genes. We employed Kaplan-Meier methods and cox univariate analysis to explore the prognostic value of the identified candidate gene Coiled-coil domain containing 50 (CCDC50). Additionally, we used DLBCL cell lines and mouse models to explore the functions and mechanisms of CCDC50. Finally, we isolated CCDC50-bearing exosomes from clinical patients to study the correlation between these exosomes and disease severity. Our results demonstrated that CCDC50 not only showed significantly positive correlations with ABC subtype, tumor stage and number of extranodal sites, but also suggested poor outcomes in DLBCL patients. We further found that CCDC50 promoted ABC-DLBCL proliferation in vitro and in vivo. Mechanistically, CCDC50 inhibited ubiquitination-mediated c-Myc degradation by stimulating the PI3K/AKT/GSK-3ß pathway. Moreover, CCDC50 expression was positively correlated with c-Myc at protein levels in DLBCL patients. Additionally, in two clinical cohorts, the plasma CCDC50-positive exosomes differentiated DLBCL subtypes robustly (AUC > 0.80) and predicted disease severity effectively (p < 0.05). Our findings suggest that CCDC50 likely drives disease progression in ABC-DLBCL patients, and the CCDC50-bearing exosome holds great potential as a non-invasive biomarker for subtype diagnosis and prognosis prediction of DLBCL patients.

18.
Ann Hematol ; 102(9): 2387-2395, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37278748

RESUMO

B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84-5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma.


Assuntos
Doenças Pulmonares Intersticiais , Linfoma de Células B , Pneumonia por Pneumocystis , Humanos , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/prevenção & controle , Lipossomos , Pontuação de Propensão , Rituximab/efeitos adversos , Vincristina/efeitos adversos , Prednisona , Doxorrubicina/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/prevenção & controle , Doenças Pulmonares Intersticiais/complicações , Ciclofosfamida , Polietilenoglicóis , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/complicações , Estudos Retrospectivos
19.
Am J Hematol ; 98(10): 1579-1587, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37466271

RESUMO

Ruxolitinib has demonstrated efficacy in patients with myelofibrosis (MF). However, substantial number of patients may not respond after 3-6 months of treatment or develop resistance over time. In this phase 2 trial, patients with a current diagnosis of intermediate or high-risk MF who either had an inadequate splenic response or spleen regrowth after ruxolitinib treatment were enrolled. All patients received jaktinib 100 mg Bid. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR 35) at week 24. The secondary endpoints included change of MF-related symptoms, anemic response, and safety profile. From July 6, 2021, to January 24, 2022, 34 ruxolitinib-refractory or relapsed patients were enrolled, 52.9% (18 of 34) were DIPSS intermediate 2 or high risk. SVR 35 at week 24 was 32.4% (11 of 34, 95% CI 19.1%-49.2%) in all patients and 33.3% (6 of 18, 95% CI 16.3%-56.3%) in the intermediate 2 or high-risk group. A total of 50% (8 of 16) transfusion-independent patients with hemoglobin (HGB) <100 g/L at baseline had HGB elevation ≥20 g/L within 24 weeks. Furthermore, 46.4% (13 of 28) of patients had a ≥ 50% decrease in the total symptom score (TSS 50) at week 24. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were thrombocytopenia (32.4%), anemia (32.4%), and leukocytosis (20.6%). In total, 13 (38.2%) of 34 patients had serious adverse events (SAE), of which drug-related SAEs were found in 5 patients (14.7%). These results indicate that jaktinib can be a promising treatment option for patients with MF who have either become refractory to or relapsed after ruxolitinib treatment.


Assuntos
Inibidores de Janus Quinases , Mielofibrose Primária , Humanos , Inibidores de Janus Quinases/efeitos adversos , Mielofibrose Primária/diagnóstico , Pirimidinas/efeitos adversos , Nitrilas , Resultado do Tratamento
20.
Acta Haematol ; 146(4): 293-306, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36812897

RESUMO

INTRODUCTION: Genetic landscape, disease characteristics, and clinical outcomes of young adults with myeloproliferative neoplasms (MPNs) were reported. However, data on patient-reported outcomes (PROs) in young adults with MPNs were rare. METHODS: We conducted a multicenter, cross-sectional study to compare the PROs in respondents with thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) by age at survey, including the young group (18-40 years), middle-aged group (41-60 years), and elderly group (>60 years). RESULTS: Of the 1,664 respondents with MPNs, 349 (21.0%) were young including 244 (69.9%) with ET, 34 (9.7%) with PV, and 71 (20.3%) with MF. In multivariate analyses, the young groups with ET and MF were associated with the lowest MPN-10 scores among the 3 age groups; those with MF, highest proportion of reporting negative impact of disease and therapy on their daily life and work. The young groups with MPNs had the highest physical component summary scores but the lowest mental component summary scores in those with ET. The young groups with MPNs were most concerned about fertility; those with ET, treatment-related adverse events and long-term efficacy of treatment. CONCLUSIONS: We concluded that young adults with MPNs have different PROs compared with middle-aged and elderly patients.


Assuntos
Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Idoso , Pessoa de Meia-Idade , Humanos , Adulto Jovem , Adolescente , Adulto , Estudos Transversais , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/terapia , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/terapia , Mielofibrose Primária/genética , Medidas de Resultados Relatados pelo Paciente
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