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1.
Lancet Oncol ; 21(10): e477-e487, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002443

RESUMO

The use of total body irradiation as part of conditioning regimens for acute leukaemia is progressively declining because of concerns of late toxic effects and the introduction of radiation-free regimens. Total marrow irradiation and total marrow and lymphoid irradiation represent more targeted forms of radiotherapy compared with total body irradiation that have the potential to decrease toxicity and escalate the dose to the bone marrow for high-risk patients. We review the technological basis and the clinical development of total marrow irradiation and total marrow and lymphoid irradiation, highlighting both the possible advantages as well as the current roadblocks for widespread implementation among transplantation units. The exact role of total marrow irradiation or total marrow and lymphoid irradiation in new conditioning regimens seems dependent on its technological implementation, aiming to make the whole procedure less time consuming, more streamlined, and easier to integrate into the clinical workflow. We also foresee a role for computer-assisted planning, as a way to improve planning and delivery and to incorporate total marrow irradiation and total marrow and lymphoid irradiation in multi-centric phase 2-3 trials.


Assuntos
Transplante de Medula Óssea , Medula Óssea/efeitos da radiação , Leucemia Mieloide Aguda/terapia , Irradiação Linfática , Condicionamento Pré-Transplante , Humanos , Irradiação Linfática/efeitos adversos , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/tendências , Resultado do Tratamento , Irradiação Corporal Total/efeitos adversos
2.
Medicine (Baltimore) ; 99(35): e22064, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871966

RESUMO

RATIONALE: Patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have poor prognosis. Many patients are not eligible for 2nd HSCT due to organ dysfunction or other complications that prevent them from tolerating conditioning chemotherapy. In those ineligible patients for 2nd HSCT with myeloablative conditioning regimen, reduced intensity conditioning (RIC) are often used. RIC regimens are less toxic but has a less direct anti-tumor efficacy so that RIC regimens are not suitable for the patients with high tumor burden. To overcome this dilemma, Gemtuzumab Ozogamicin (GO) has been used as a part of RIC regimens to add anti-tumor efficacy. We report here a relapsed AML patient who was treated with GO monotherapy followed by stem cell infusion. PATIENT CONCERNS: A 25-year-old male with AML experienced relapse 9 months after allo-HSCT. DIAGNOSIS: Since he had mild renal and cardiac dysfunction and his AML did not progress rapidly, we decided not to give him an intensive chemotherapy. However, after azacitidine (AZA) and donor lymphocyte infusion therapy, his leukemic blasts did not decrease. INTERVENTIONS: Originally, we had planned to proceed with a 2nd allo-HSCT with RIC regimen that consisted of fludarabine, melphalan and fractionated GO (3 mg/m/dose) on day -21, -18, and -15. However, the patient developed appendicitis after the last dose of GO when his neutrophil was 0 cells/µl. Based on his medical acuity, we terminated the rest of the patients conditioning regimen and the patient did not receive any further chemotherapeutics. The patient was still infused with peripheral blood stem cells from the donor on day 0. OUTCOMES: His appendicitis was resolved by antibiotics without surgery. His AML has been in CR more than 18 months under AZA maintenance therapy. LESSONS: GO monotherapy could be a conditioning regimen of 2nd allo HSCT from the same donor as the first HSCT for relapsed AML patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Gemtuzumab/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Adulto , Humanos , Masculino , Recidiva , Transplante Homólogo
3.
Lancet Haematol ; 7(10): e715-e723, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32976751

RESUMO

BACKGROUND: The interferon lambda 4 gene (IFNL4) regulates immune responses by controlling the production of IFNλ4, a type III interferon. We hypothesised that IFNλ4 could play a role in infection clearance or alloreactivity in patients with acute leukaemia who received a myeloablative 10/10 HLA-matched haematopoietic stem-cell transplantation (HSCT). Therefore, we aimed to assess the association between recipient and donor IFNL4 genotype with post-HSCT survival outcomes in patients with acute leukaemia. METHODS: We did a two-stage retrospective cohort study using the Center for International Blood and Marrow Transplant Research (CIBMTR) repository and database, in which nearly all patients underwent the procedure in the USA. We included patients with acute myeloid leukaemia or acute lymphocytic leukaemia, who received a HSCT at any age from an unrelated 10/10 HLA-matched donor, with a myeloablative conditioning regimen, between Jan 1, 2000, and Dec 31, 2008, and had a pre-HSCT recipient or donor blood sample available. The discovery dataset included patients from an existing National Cancer Institute (NCI) cohort of the CIBMTR database, in which donor and recipient IFNL4 polymorphisms (rs368234815, rs12979860, and rs117648444) were genotyped with TaqMan assays. According to their genotype, donors and recipients were categorised into IFNL4-positive, if they had at least one copy of the allele that supports the production of IFNλ4, or IFNL4-null for the analyses. The findings were independently validated with patients from the DISCOVeRY-BMT cohort (validation dataset) with existing Illumina array genotype data. We also did a combined analysis using data from patients included in both the NCI and DISCOVeRY-BMT cohorts. FINDINGS: We assessed 404 patients (who had a HSCT from Jan 9, 2004, to Dec 26, 2008) in the discovery dataset and 1245 patients in the validation dataset (HSCT Jan 7, 2000, to Dec 26, 2008). The combined analysis included 1593 overlapping participants in both cohorts. Donor, but not recipient IFNL4-positive genotype was associated with increased risk of non-relapse mortality (HR 1·60, 95% CI 1·23-2·10; p=0·0005 in the discovery dataset; 1·22, 1·05-1·40; p=0·0072 in the validation dataset; and 1·27, 1·12-1·45; p=0·0001 in the combined dataset). Associations with post-HSCT overall survival were as follows: HR 1·24, 95% CI 1·02-1·51; p=0·034 in the discovery dataset; 1·10, 0·98-1·20; p=0·10 in the validation dataset; and 1·11, 1·02-1·22; p=0·018 in the combined dataset. INTERPRETATION: Prioritising HSCT donors with the IFNL4-null genotype might decrease non-relapse mortality and improve overall survival without substantially limiting the donor pool. If these findings are validated, IFNL4 genotype could be added to the donor selection algorithm. FUNDING: The National Cancer Institute Intramural Research Program. For full funding list see Acknowledgments.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Interleucinas/genética , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Feminino , Genótipo , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
5.
Ann Hematol ; 99(10): 2417-2427, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32862286

RESUMO

For most acute myeloid leukemia (AML) patients, an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of sustained remissions and long-term survival. At diagnosis, high expression of the AML-associated genes BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma-1) were repeatedly linked to inferior outcomes in patients consolidated with chemotherapy while data for patients receiving HSCT remain limited. Using clinically applicable digital droplet PCR assays, we analyzed the diagnostic BAALC/ABL1 and MN1/ABL1 copy numbers in 302 AML patients. High BAALC/ABL1 and MN1/ABL1 copy numbers associated with common adverse prognostic factors at diagnosis. However, while high diagnostic copy numbers of both genes associated with shorter event free survival (EFS) and overall survival (OS) in patients receiving chemotherapy, there was no prognostic impact in patients undergoing HSCT. Our data suggests that the adverse prognostic impact of high BAALC and MN1 expression are mitigated by allogeneic HSCT. But preHSCT BAALC/ABL1 and MN1/ABL1 assessed in remission prior to HSCT remained prognosticators for EFS and OS independent of the diagnostic expression status. Whether allogeneic HSCT may improve survival for AML patients with high diagnostic BAALC or MN1 expression should be investigated prospectively and may improve informed decisions towards individualized consolidation options in AML.


Assuntos
Medula Óssea/patologia , Leucemia Mieloide Aguda/terapia , Proteínas de Neoplasias/genética , Transplante de Células-Tronco de Sangue Periférico , Transativadores/genética , Proteínas Supressoras de Tumor/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/química , Terapia Combinada , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Reação em Cadeia da Polimerase/métodos , Prognóstico , Proteínas Proto-Oncogênicas c-abl/genética , Transativadores/biossíntese , Resultado do Tratamento , Proteínas Supressoras de Tumor/biossíntese , Adulto Jovem
7.
Rinsho Ketsueki ; 61(6): 665-672, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32624541

RESUMO

In Japan, acute myeloid leukemia (AML) accounts for approximately 25% of all pediatric leukemias, with approximately 150 cases of newly diagnosed AML occurring annually. Approximately 10% of patients have primary induction failure and 30% of patients, who initially achieve remission in primary treatments, subsequently relapse. Novel treatment modalities need to be developed to further improve the prognosis of pediatric AML patients. AML is a heterogeneous genetic disease characterized by changes in the genome of hematopoietic progenitor cells. Recent studies that have made progress in research related to the pathogenesis of AML have suggested that genotype-specific treatment strategies are associated with increased efficacy. Potential new therapeutic alternatives for pediatric AML include: tyrosine kinase inhibitors, monoclonal or bispecific T-cell engager antibodies, chimeric antigen receptor T-cell therapy, and metabolic agents. This review highlights the current landscape of novel therapeutic approaches for childhood AML, including the results of both preclinical and clinical trials, as well as introducing the results of several preceding adult clinical studies, which could potentially be translated into pediatric AML patients.


Assuntos
Leucemia Mieloide Aguda , Criança , Humanos , Imunoterapia , Imunoterapia Adotiva , Japão , Leucemia Mieloide Aguda/terapia , Recidiva
9.
Ann Hematol ; 99(9): 2201-2203, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32699943
10.
Zhonghua Xue Ye Xue Za Zhi ; 41(5): 365-372, 2020 May 14.
Artigo em Chinês | MEDLINE | ID: mdl-32536132

RESUMO

Objective: To compare differences of autologous and unrelated donor stem cell transplantation (auto-HSCT and URD-HSCT) for adults with primary acute myeloid leukemia (AML) in first complete remission (CR(1)) from a single center and to investigate the appropriate patients for the 2 types of transplant. Methods: In this retrospective investigation, we studied adults with primary AML who received auto-HSCT and URD-HSCT from March 2008 to November 2018. Overall survival (OS) , leukemia-free survival (LFS) , relapse, transplant-related mortality (TRM) , and hematopoietic reconstitution were compared along with the prognostic value of cytogenetics. Results: A total of 147 adult patients were enrolled in this study (n=87 for auto-HSCT and n=60 for URD-HSCT) . Baseline characteristics were comparable between the 2 groups. The accumulative neutrophil engraftment rate at +30 days was not statistically different between the 2 groups[92.6% (95% CI 86.9%-98.3%) vs 98.3% (95% CI 95.0%-100.0%) , P=0.270], whereas the accumulative platelet engraftment rate at +60 days was significantly lower in the auto-HSCT group[83.6% (95% CI 75.8%-91.4%) vs 93.3% (95% CI 87.0%-99.6%) , P<0.001]. In patients undergoing URD-HSCT, the accumulative incidences of acute GVHD (aGVHD) and grade Ⅱ-Ⅳ aGVHD were 56.7% (95% CI 43.0%-68.2%) and 16.7% (95% CI 8.5%-27.2%) , and the incidences of chronic GVHD (cGVHD) and extensive cGVHD were 33.3% (95% CI 21.7%-45.4%) and 15.0% (95% CI 7.3%-25.2%) , respectively. After a median follow-up of 53.8 (0.8-127.8) months, patients in the 2 groups demonstrated comparable OS and LFS at 5 years after transplant[71.7% (95% CI 61.7%-81.7%) vs 67.8% (95% CI 55.8%-79.8%) , P=0.556; 64.6% (95% CI 54.4%-74.8%) vs 68.1% (95% CI 56.3%-79.9%) , P=0.642]. Patients in the auto-HSCT group showed significantly higher incidence of relapse at 5 years after transplant[31.9% (95% CI 22.2%-42.1%) vs 15.1% (95% CI 7.4%-25.6%) , P=0.015] and significantly lower incidence of TRM[3.4% (95% CI 0.9%-8.9%) vs 16.7% (95% CI 8.5%-27.2%) , P=0.006] compared with the URD group. HLA mismatching had no effects on the incidences of hematopoietic reconstitution, GVHD, OS, LFS, relapse, and TRM. Patients of cytogenetically favorable and intermediate risk demonstrated comparable OS and LFS after auto-HSCT and URD-HSCT, while patients of poor risk had significantly higher relapse and lower LFS after auto-HSCT. Conclusions: In this study, adults with primary AML in CR(1) demonstrated relatively higher relapse but lower TRM after auto-HSCT, resulting in comparable survival to that of URD-HSCT. In the absence of matched sibling donors, patients of cytogenetically poor risk should receive URD-HSCT in order to achieve lower relapse and better survival.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos , Transplante Autólogo , Doadores não Relacionados
11.
Ann Hematol ; 99(8): 1855-1862, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32564196

RESUMO

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Aloenxertos , Clofarabina/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Taxa de Sobrevida
12.
Health Qual Life Outcomes ; 18(1): 199, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576289

RESUMO

BACKGROUND: Patients with acute leukaemia (AL) usually require prolonged periods of hospitalisation. The treatment and clinical symptoms may lead to patients' supportive care needs (SCNs) not being met and impairs their quality of life (QoL). Studies on QoL and SCNs among AL patients are limited. This study aimed to identify the unmet SCNs and its relation to QoL of adult AL patients in China. METHODS: This multicentre cross-sectional study recruited 346 participants to complete a self-developed questionnaire, detailing demographic information and disease-related variables. A 34-item Supportive Care Needs Survey (SCNS-SF34) was used to identify unmet SCNs, and the Functional Assessment of Cancer Therapy-Leukaemia (FACT-Leu) questionnaire measured patients' QoL. RESULTS: Unmet SCN rates for the 34 items ranged from17.6 to 81.7%. Patients' needs were high for health systems and information, but low in the sexual domain. The results reveal nine factors associated with the unmet SCNs of adult AL patients, including marital status, original residence, age, education, occupation, other diseases, chemotherapy course, disease course, and treatment stage (p < 0.05). The total score of the FACT-Leu negatively correlated with the SCNS-SF34 in the physical/daily living (r = - 0.527, p < 0.01), psychological (r = - 0.688, p < 0.01), sexual (r = - 0.170, p < 0.01), patient care and support (r = - 0.352, p < 0.01), and health systems and information (r = - 0.220, p < 0.01) domains. CONCLUSIONS: Adult AL patients exhibit a high demand for unmet SCNs, especially in the domain of health systems and information. There was a significant association between patients' unmet SCNs and QoL. Future research should develop tailored interventions to address the unmet SCNs of adult AL patients, to further improve their QoL.


Assuntos
Necessidades e Demandas de Serviços de Saúde , Leucemia Mieloide Aguda/psicologia , Qualidade de Vida , Adolescente , Adulto , China , Estudos Transversais , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
13.
Proc Natl Acad Sci U S A ; 117(25): 14331-14341, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513686

RESUMO

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with approximately four new cases per 100,000 persons per year. Standard treatment for AML consists of induction chemotherapy with remission achieved in 50 to 75% of cases. Unfortunately, most patients will relapse and die from their disease, as 5-y survival is roughly 29%. Therefore, other treatment options are urgently needed. In recent years, immune-based therapies have led to unprecedented rates of survival among patients with some advanced cancers. Suppression of T cell function in the tumor microenvironment is commonly observed and may play a role in AML. We found that there is a significant association between T cell infiltration in the bone marrow microenvironment of newly diagnosed patients with AML and increased overall survival. Functional studies aimed at establishing the degree of T cell suppression in patients with AML revealed impaired T cell function in many patients. In most cases, T cell proliferation could be restored by blocking the immune checkpoint molecules PD-1, CTLA-4, or TIM3. Our data demonstrate that AML establishes an immune suppressive environment in the bone marrow, in part through T cell checkpoint function.


Assuntos
Medula Óssea/metabolismo , Leucemia Mieloide Aguda/metabolismo , Linfócitos T/metabolismo , Microambiente Tumoral/fisiologia , Medula Óssea/imunologia , Antígeno CTLA-4/metabolismo , Proliferação de Células , Citocinas/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T/imunologia
15.
Cancer Sci ; 111(7): 2472-2481, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32391628

RESUMO

In this phase II multicenter study (JALSG AML209-FLT3-SCT), we aimed to prospectively elucidate the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) for FLT3-internal tandem duplication (ITD)-positive AML. Newly diagnosed de novo AML patients with FLT3-ITD were enrolled at the achievement of CR1 and received allo-HSCT as soon as possible after the first consolidation therapy. Mutations of 57 genes in AML cells at diagnosis were also analyzed. Among 48 eligible patients with a median age of 38.5 (17-49) years, 36 (75%) received allo-HSCT at a median of 108 days after CR1. The median follow-up was 1726 days. The primary end-point, 3-year disease-free survival (DFS) based on an intent to treat analysis, was 43.8% (95% confidence interval [CI], 30%-57%), suggesting the efficacy of this treatment because the lower limit of the 95% CI exceeded the threshold response rate of 20%. The 3-year overall survival, post-transplant DFS, and non-relapse mortality rates were 54.2% (95% CI, 39%-67%), 58.3% (95% CI, 41%-72%), and 25.0% (95% CI, 12%-40%), respectively. The median ITD allelic ratio (AR) was 0.344 (0.006-4.099). Neither FLT3-ITD AR nor cooccurring genetic alterations was associated with a poor DFS. This prospective study indicated the efficacy and safety of allo-HSCT for FLT3-ITD AML patients in CR1. This study was registered at: www.umin.ac.jp/ctr/ as #UMIN000003433.


Assuntos
Expansão das Repetições de DNA , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
16.
Jpn J Clin Oncol ; 50(8): 889-896, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32458984

RESUMO

OBJECTIVE: The relationship between body mass index and overall survival has been controversial in patients who suffered from hematological malignancies and underwent hematopoietic stem cell transplantation. METHODS: We collected the data of 686 acute leukemia patients who received only one allogeneic hematopoietic stem cell transplantation in our center from 2008 to 2017. Patients were divided into four groups (underweight, normal weight, overweight and obesity) according to their body mass index pre-hematopoietic stem cell transplantation. RESULTS: 56.4% of patients had normal body mass indices, 17.3% were underweight, 20.4% were overweight and 5.8% were with obesity. Concerning long-term follow-up, the probability of overall survival was significantly lower in overweight (P = 0.010) and patients with obesity (P = 0.065) as compared with normal weight patients, and no statistically significant difference between underweight and normal weight individuals (P = 0.810). The results demonstrated that higher body mass index was associated with poorer overall survival (hazard ratio: 1.79; 95% confidence interval: 1.33-2.40, P < 0.001) and shorter leukemia-free survival (hazard ratio: 1.78; 95% confidence interval: 1.35-2.34, P < 0.001). Additionally, patients exhibiting a higher body mass index were more likely to face the problem of relapse (30.6 vs 20.9%, P < 0.001). Furthermore, non-relapse mortality of patients with obesity was statistically higher than normal weight patients (22.5 vs 9.6%, P = 0.027). Besides, individuals with a higher abdominal girth had shorter survival (hazard ratio: 1.73; 95% confidence interval: 1.29-2.31, P < 0.001) and higher relapse rate (hazard ratio: 1.78; 95% confidence interval: 1.29-2.45, P = 0.001) as compared with those with a lower abdominal girth. CONCLUSION: Our results indicate that obesity at pre-hematopoietic stem cell transplantation stage, whether characterized by higher body mass index or abdominal girth, is correlated with poorer outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Obesidade/complicações , Adolescente , Adulto , Criança , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Sobrepeso/complicações , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Magreza/complicações , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
18.
Ann Hematol ; 99(6): 1351-1360, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32363416

RESUMO

Acute myeloid leukemia (AML) represents the most common indication for allogeneic hematopoietic cell transplantation (HCT). This study aimed to address the implementation status of allogeneic HCT for adults with AML in Japan and to provide a comprehensive overview of post-transplant outcomes. For this purpose, we analyzed data of 15,186 patients undergoing allogeneic HCT between 1992 and 2016 who were consecutively reported to the Japanese nationwide transplantation registry. The constant increase in the annual number of transplantations was clearly attributable to the growth of unrelated transplantation, and umbilical cord blood transplantation currently accounts for one-third of all allogeneic HCTs. The proportion of older patients has increased steadily since 2000, approximately, in parallel with the introduction of reduced-intensity conditioning. The probability of overall survival (OS) was estimated at 41% (95% confidence interval (CI), 40-42%) for the entire cohort, 56% (95% CI, 55-57%) for patients transplanted in complete remission (CR), and 22% (95% CI, 21-23%) for those transplanted in non-CR. Multivariate analysis identified age, sex, performance status, disease status, cytogenetic risk, donor type, graft source, sex mismatch between the donor and the recipient, and year of transplantation as factors significantly associated with OS. These findings represent the real-world data in Japan, showing the changes in transplantation practice and a detailed estimation of post-transplant outcomes.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/tendências , Transplante Homólogo/métodos , Transplante Homólogo/tendências , Adulto Jovem
20.
Mol Immunol ; 123: 7-17, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32387766

RESUMO

The identification of T cell epitopes derived from tumour specific antigens remains a significant challenge for the development of peptide-based vaccines and immunotherapies. The use of mass spectrometry-based approaches (immunopeptidomics) can provide powerful new avenues for the identification of such epitopes. In this study we report the use of complementary peptide antigen enrichment methods and a comprehensive mass spectrometric acquisition strategy to provide in-depth immunopeptidome data for the THP-1 cell line, a cell line used widely as a model of human leukaemia. To accomplish this, we combined robust experimental workflows that incorporated ultrafiltration or off-line reversed phase chromatography to enrich peptide ligand as well as a multifaceted data acquisition strategy using an Orbitrap Fusion LC-MS instrument. Using the combined datasets from the two ligand enrichment methods we gained significant depth in immunopeptidome coverage by identifying a total of 41,816 HLA class I peptides from THP-1 cells, including a significant number of peptides derived from different oncogenes or over expressed proteins associated with cancer. The physicochemical properties of the HLA-bound peptides dictated their recovery using the two ligand enrichment approaches and their distribution across the different precursor charge states considered in the data acquisition strategy. The data highlight the complementarity of the two enrichment procedures, and in cases where sample is not limiting, suggest that the combination of both approaches will yield the most comprehensive immunopeptidome information.


Assuntos
Antígenos de Neoplasias/análise , Mineração de Dados/métodos , Epitopos de Linfócito T/imunologia , Leucemia Mieloide Aguda/metabolismo , Peptídeos/análise , Proteoma/análise , Antígenos de Neoplasias/química , Antígenos de Neoplasias/imunologia , Células Cultivadas , Cromatografia Líquida/métodos , Bases de Dados de Proteínas , Humanos , Imunoterapia/métodos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Ligantes , Espectrometria de Massas/métodos , Biblioteca de Peptídeos , Peptídeos/química , Proteoma/química , Proteômica/métodos , Células THP-1
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