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Background: The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission. Objectives: This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML. Design: This was a retrospective study. Methods: Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction. Results: This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8-98.7) and 90.5% (95% CI: 81.3-95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction (p = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients. Conclusion: Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.
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Background: The use of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA) has long been considered the standard regimen for preventing chemotherapy-induced nausea and vomiting (CINV) prior to hematopoietic stem cell transplantation (HSCT). However, their therapeutic outcomes have been unsatisfactory. NEPA, an oral formulation combining the neurokinin-1 receptor antagonist netupitant and the 5HT3RA palonosetron, has received regulatory approval for the management of highly and moderately emetogenic chemotherapy. This study aims to compare the efficacy of NEPA with that of 5HT3RA alone in preventing CINV among patients undergoing multiday conditioning chemotherapy prior to HSCT. Patients and methods: We conducted a retrospective analysis of patients who underwent HSCT between September 2019 and September 2022. Efficacy outcomes were assessed based on the rates of patients achieving complete response (CR: no emesis and no use of rescue medication), complete control (CC: CR without significant nausea), no vomiting, and no significant nausea. Results: The NEPA group consisted of 106 patients, while the 5HT3RA group included 107 patients. The NEPA group exhibited significantly higher rates of CR compared to the 5HT3RA group during the overall phase (71.7% vs. 32.7%, P<0.001), acute phase (78.3% vs. 43.0%, P<0.001), and delayed phase (84.9% vs. 58.9%, P<0.001). Similarly, rates of CC, no vomiting, and no significant nausea were significantly better in the NEPA group across all phases (P<0.001). Conclusion: NEPA demonstrated superior efficacy compared to 5HT3RA in preventing CINV during all phases of multiday conditioning regimens among patients undergoing HSCT.
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Natural killer (NK) cell based immunotherapy is an emerging strategy in hematologic malignancies because allogeneic NK cells can provide potent antitumor immunity without inducing graft-versus-host disease. Thus, we expanded cord blood-derived NK (CB-NK) cells ex vivo from random (MHC mismatched and KIR mismatched) donors, and investigate the feasibility and efficacy of repeated infusions CB-NK cells as maintenance therapy after autologous hematopoietic stem cell transplantation (ASCT). Thirty-one patients with acute myeloid leukemia and high-risk lymphoma received ASCT and the adoptive CB-NK cell multiple infusions for maintenance therapy. Patients received a median dose of 5.98 × 107/kg (range, 1.87-17.69 × 107/kg) CB-NK cells and 23 patients completed four infusions, 8 patients received three infusions. Only mild infusion reactions occurred in 15.5% of 116 infusions. Compared to a contemporaneous cohort of 90 patients who did not receive NK cell therapy, the adoptive transfer of CB-NK cells as maintenance treatment showed a tendency of difference in decreasing the relapse rate between CB-NK group and control group (9.7% vs 24.4%). The patients who receiving NK cell infusions had a better PFS and OS than controls (4 year PFS, 84.4 ± 8.3% vs 73.5 ± 5.4%; and 4 year OS, 100% vs 78.1 ± 5.4%) . These findings demonstrate safety and validity of maintenance therapy using CB-NK cells multiple infusions after ASCT, and it is worthy of further clinical trial verification.
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Sangue Fetal , Transplante de Células-Tronco Hematopoéticas , Humanos , Projetos Piloto , Células Matadoras Naturais , Transplante AutólogoRESUMO
Acute graft versus host disease (aGvHD) is a severe complication that arises in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and remains the primary cause of nonrelapse mortality (NRM). The MAGIC algorithm probability (MAP) has been proposed to identify patients at intermediate and high risk of developing aGvHD. The levels of suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3α (Reg3α) were assessed, and MAP was calculated on days 7, 14, 21, and 28 after allo-HSCT. Based on the MAP results, patients were classified into low-, intermediate-, or high-risk groups for the development of aGvHD. Random assignment was performed to allocate intermediate- or high-risk patients to receive preemptive therapy with methylprednisolone or not. The 100-day cumulative incidences of grade 2 or higher (35.5% ± 8.6%) and grade 3 or higher (12.9% ± 6.0%) aGvHD in the methylprednisolone group were significantly lower than those in the control group (66.7% ± 7.9%, p = .01; 42.9% ± 8.4%, p = .01), and similar to those observed in the low-risk group (31.7% ± 7.3%, p = .75; 2.4% ± 2.4%, p = .08). The 6-month cumulative incidences of NRM were 14.1% ± 6.6%, 22.7% ± 7.1%, and 2.4% ± 2.4% in the methylprednisolone, control, and low-risk groups, respectively, with no significant difference between the methylprednisolone and control groups (p = .29). Methylprednisolone did not increase infections (p = .34). The 100-day cumulative incidences of cytomegalovirus (CMV) reactivation were 67.7% ± 8.4%, 65.6% ± 8.4%, and 46.3% ± 7.8% (p = .08), and those of grade 2 or higher hemorrhagic cystitis were 29.0% ± 8.2%, 45.2% ± 8.9% and 22.0% ± 6.5% (p = .11) in the methylprednisolone, control, and low-risk groups, respectively. MAP-guided preemptive therapy for aGvHD is promising. The long-term efficacy and safety remain to be investigated.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Metilprednisolona/uso terapêutico , Transplante Homólogo/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores de Risco , Algoritmos , Estudos Retrospectivos , Doença AgudaRESUMO
Background: The prognosis of patients with peripheral T-cell (PTCL) or lymphoblastic T-cell lymphoma (T-LBL) remains poor under current conditioning regimens before receiving autologous stem cell transplantation (ASCT). Methods: Patients with PTCL or T-LBL were enrolled to receive ASCT using the conditioning regimen of chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Positron emission tomography-computed tomography (PET/CT) was used to evaluate the response to ASCT. Overall survival (OS) and progression-free survival (PFS) were employed to assess the patient outcome, and adverse events were used to assess the regimen's safety. The survival curve was estimated via the Kaplan-Meier method. Results: Twenty-five PTCL and 11 T-LBL patients were recruited. The median time to neutrophile and platelet engraftments was 10 days (8-13 days) and 13 days (9-31 days), respectively. The 3-year PFS and OS were 81.3 ± 7.2% and 88.5 ± 5.4% for all patients; 92.0 ± 5.4% and 81.2 ± 8.8% for PTCL patients; and both 81.8 ± 11.6% for T-LBL patients, respectively. The 3-year PFS and OS were both 92.9 ± 4.9% for patients with complete response (CR) but 50.0 ± 17.7% and 75.0 ± 15.3% for patients with non-CR, respectively. Infection was the most common non-hematological toxicity, and all toxicities were mild and controllable. Conclusions: ChiCGB was a potentially effective and well-tolerated conditioning regimen to improve the prognosis of patients with aggressive T-cell lymphoma. Future randomized controlled trials are needed to assess ChiCGB as a conditioning regimen for ASCT.
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PURPOSE: Primary adrenal lymphoma (PAL) is an extremely rare entity, there were few cases have been reported. We report a 52-year-old female with unilateral PAL. METHODS: Case report. RESULTS: A rapid biopsy resulted in the diagnosis of diffuse large B-cell lymphoma after excluding pheochromocytoma. R-CHOP combined with CNS prophylaxis and autologous stem cell transplant (ASCT) has produced an excellent outcome. CONCLUSIONS: Primary adrenal lymphoma (PAL) is a sporadic and highly invasive malignant disease. Symptoms are atypical, making it difficult to obtain an accurate early diagnosis. Adrenal incidentaloma is usually the first clinical manifestation. Some patients may have fever, night sweats, weight loss, and lumbar and abdominal pain. Adrenal insufficiency (AI) may occur in a subset of patients. The identification of other adrenal malignancies, especially catecholamine-secreting tumors, is particularly important for early diagnosis.
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Neoplasias das Glândulas Suprarrenais , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante Autólogo , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Transplante de Células-Tronco , Neoplasias das Glândulas Suprarrenais/diagnósticoRESUMO
The treatment of patients with acute myeloid leukemia (AML) who are intolerable to intensive chemotherapy remains to be further explored. Recent studies have shown that venetoclax combined with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) may have a good effect on these patients. Given the lack of a comprehensive analysis of the efficacy and safety of such treatment, the aim of this review was to assess the efficacy and safety of venetoclax plus HMAs or LDAC for untreated AML patients who are ineligible for intensive chemotherapy. A systematic literature review was conducted in the PubMed, Embase, and Cochrane databases up to April 30, 2021. A total of four clinical trials including 440 patients were eligible for this meta-analysis. The pooled complete remission (CR) and complete remission plus complete remission with incomplete blood count recovery (CR/CRi) rates were 0.40 (95% CI 0.26-0.55) and 0.64 (95% CI 0.49-0.77), respectively. The median overall survival time was 11.7 (95% CI 10.15-14.18) months. The most common adverse events (AEs) of any grade were nausea (57%), diarrhea (42%), and hypokalemia (36%). The most common AEs of grade ≥ 3 were febrile neutropenia (38%) and thrombocytopenia (35%). The pooled 30-day mortality rate in our study was 5%. The improved remission rate and tolerance make venetoclax combined with HMAs or LDAC an attractive induction therapy option for untreated AML patients who are unsuitable for intensive chemotherapy.
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Citarabina , Leucemia Mieloide Aguda , Humanos , Citarabina/efeitos adversos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/etiologia , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosAssuntos
Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Humanos , Mobilização de Células-Tronco Hematopoéticas , Terapia de Salvação , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Células-Tronco Hematopoéticas/metabolismo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Antígenos CD34/metabolismo , Benzilaminas/metabolismoRESUMO
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) is a high-risk disease subtype with a dismal prognosis. Inhibiting BCR-ABL kinase alone is insufficient to eradicate Ph+ALL clones, and alternative BCR-ABL-dependent and -independent pathways need to be targeted as an effective strategy. Our study revealed that the combination of dasatinib and interferon-α showed synergistic activity against Ph+ALL, inducing mitochondrial dysfunction and causing necrosis-like cell lysis. Mechanistic studies showed that the induced cell death was caspase-3-independent. Canonical necroptosis signals, such as RIP1 and MLKL, were not activated; instead, the pyroptosis executor Gasdermin D was upregulated expression and activated. The expression levels of extracellular ATP and IL-1ß were also upregulated, both of which are markers of pyroptotic cell death. In a murine Ph+ALL model, the dual drug treatment prolonged the survival of tumor-bearing mice. More importantly, we incorporated the dual drugs to maintenance therapy in 39 patients who were unfit for allogeneic stem cell transplantation (allo-HSCT). The median follow-up was 28.5 months, the 4-year disease-free survival and overall survival rates were 52.2% and 65.2%, respectively. Our data suggest that the combination of dasatinib and interferon-α has potential synergistic activity against Ph+ALL and shows promise as a maintenance therapy for Ph+ALL patients who are unfit for allo-HSCT.
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We report the case of a 47-year-old male patient with pigmentation of the head, face and hands, who was initially diagnosed as having primary adrenal insufficiency (Addison's disease). Laboratory testing, imaging and physical examination revealed subclinical hypothyroidism, high circulating prolactin and oestradiol concentrations, gynaecomastia, lymphadenopathy, splenomegaly and weakness of both lower limbs. These findings led us to consider whether a single or multiple diseases were present in this patient. Indeed, Addison's disease can represent one aspect of a wider systemic disease. Therefore, we performed further examinations, and found high serum M protein (5.1%) and vascular endothelial growth factor [1005.30 pg/mL (normal range 0 to 142 pg/mL)] concentrations. As a consequence, we diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. Consequently, when a single disease cannot fully explain the multiple symptoms and signs of one patient, clinicians should consider the possibility of the presence of a wider syndrome and undertake more detailed diagnostic testing.
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Doença de Addison , Síndrome POEMS , Doença de Addison/complicações , Doença de Addison/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/diagnóstico , Esplenomegalia , Fator A de Crescimento do Endotélio VascularRESUMO
ABSTRACTObjectives: Hereditary hyperferritinaemia cataract syndrome (HHCS) is an autosomal dominant disease characterized by high serum ferritin levels and juvenile bilateral cataracts. It is often caused by mutations in the iron response element (IRE) of the ferritin L-subunit (FTL) gene. Here, we report a 73-year-old woman who presented to clinic with persistently elevated serum ferritin and family history of juvenile bilateral cataracts in four generations.Methods: Exome sequencing was used to identify the mutation of the FTL gene. Moreover, Sanger sequencing was performed to validate the mutation in the proband. We also reviewed the FLT gene mutations in published HHCS cases to provide experience for accurate diagnosis of similar patients.Results: A heterozygous mutation at position +33 (c.-167C > T, chr19:49468598) of the FTL gene was identified in the patient.Discussion: HHCS should be considered in the differential diagnosis of hyperferritinemia, especially in the presence of normal serum iron concentration and transferrin saturation.Conclusion: For patients with unexplained hyperferritinemia and bilateral cataracts who have experienced early vision loss, the establishment of genetic counseling is essential to diagnose other family members who are at risk in time.Abbreviations: FTL: ferritin L-subunit; HHCS: hereditary hyperferritinaemia cataract syndrome; IDT: integrated DNA technologies; IRE: iron response element; IRP: iron regulatory proteins; MRI: magnetic resonance imaging; SNV: single nucleotide variant; UTR: untranslated region.
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Apoferritinas/genética , Catarata/congênito , Distúrbios do Metabolismo do Ferro/congênito , Mutação , Idoso , Alelos , Apoferritinas/sangue , Biomarcadores , Catarata/diagnóstico , Catarata/genética , Catarata/metabolismo , Catarata/terapia , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/diagnóstico , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/metabolismo , Distúrbios do Metabolismo do Ferro/terapia , Linhagem , Elementos de Resposta/genética , Avaliação de SintomasRESUMO
Cancer is a malignant disease that seriously affects human health and life. Early diagnosis and timely treatment can significantly improve the survival rate of cancer patients. Surface-enhanced Raman scattering (SERS) is an optical technology that can detect and image samples at the single-molecule level. It has the advantages of rapidity, high specificity, high sensitivity and no damage to the sample. The performance of SERS is highly dependent on the properties, size and morphology of the SERS substrate. Preparation of SERS substrates with good reproducibility and chemical stability is a key factor in realizing the wide application of SERS technology in cancer diagnosis. In this review we provide a detailed presentation of the latest research on SERS in cancer diagnosis and the detection of cancer biomarkers, mainly focusing on nanotechnological approaches in cancer diagnosis by using SERS. We also consider the future development of nanostructure-based SERS in cancer diagnosis.
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Nanoestruturas , Neoplasias , Humanos , Nanotecnologia , Neoplasias/diagnóstico por imagem , Reprodutibilidade dos Testes , Análise Espectral RamanRESUMO
Previous studies highlight the need for a more active conditioning therapy in high-risk or refractory and relapsed lymphomas. Our preclinical research shows that histone deacetylase inhibitors, such as either vorinostat or chidamide, sensitize lymphoma cells to the cytotoxic combination of cladribine, gemcitabine and busulfan, leading to cell apoptosis. To evaluate the efficacy of this chidamide-cladribine-gemcitabine-busulfan (ChiCGB) combination as a new conditioning therapy, we conducted a Phase II trial, as described here. Patients with high-risk, relapsed/refractory lymphomas received ChiCGB as conditioning therapy, after transplantation with autologous peripheral stem cells. The sample comprised 105 patients in total: 60 with B-cell non-Hodgkin lymphomas (B-NHL) and 45 with T-cell or natural killer/T-cell lymphoma (NK/T). All patients eventually achieved full hematopoietic recovery. Neutrophils and platelets were engrafted at a median of 10 days (8-14) and 13 days (8-38), respectively. There was no transplant-related mortality within 100 days of transplant. Neutropenic fever, mucositis and atopic dermatitis were the observed nonhematologic toxicities. At a median follow-up of 35.4 months, 80.6% of the patients presented with no tumor progression, and the overall survival (OS) reached as high as 86.1%. Concerning the OS rate, 94.5% of patients with B-NHL and 75.4% of patients with T-cell or NK/T lymphomas survived. These findings demonstrate the safety and validity of the proposed combined therapy for high-risk and refractory/relapsed lymphomas. Our study was registered on the Clinical Trial Registry (clinicaltrials.gov, NCT03151876).
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Aminopiridinas/administração & dosagem , Aminopiridinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Cladribina/administração & dosagem , Cladribina/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Intervalo Livre de Progressão , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Adulto Jovem , GencitabinaRESUMO
BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Although the prognostic value of BCR-ABL1 isoforms in Ph+ ALL patients has been investigated in numerous studies in the tyrosine kinase inhibitor (TKI) era, the results were still conflicting. Hence we performed herein the meta-analysis to comprehensively assess the impact of BCR-ABL1 isoforms on the clinical outcomes of Ph+ ALL patients. Systematic literature review was conducted in PubMed, Embase, and Cochrane databases with the data access date up to June 15, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Furthermore, subgroup analyses were performed to assess the robustness of the associations. Nine studies with a total number of 1582 patients were eligible for this meta-analysis. Combined HRs suggested that p210 was slightly associated with inferior event-free survival (EFS) (HR = 1.34, 95% CI 1.05-1.72). The overall survival (OS) was not significantly affected (HR = 1.15, 95% CI 0.92-1.45). In subgroup analyses, the HRs showed a trend toward adverse impact of p210 on clinical outcomes. However, the confidence intervals were not crossing the null value only in a minority of subgroups including Caucasian studies, first-generation TKI treated cohort and transplant cohort. Our findings suggested that p210 might pose a mild adverse impact on the EFS of Ph+ ALL patients. This effect might be compromised by the use of second- or third-generation TKIs. Further studies are needed to verify our conclusions.
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Proteínas de Fusão bcr-abl/genética , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Intervalo Livre de Doença , Humanos , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Isoformas de Proteínas/genéticaRESUMO
In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as a standard approach for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) achieving complete remission (CR). However, the role of autologous hematopoietic stem cell transplantation (auto-HSCT) in adult patients achieving complete molecular remission (CMR) is an alternative, less toxic treatment options, especially for the patients who lack suitable donors and are unfit for allo-HSCT. Thus, we conducted a systematic review and meta-analysis to compare the efficacy of allo-HSCT and auto-HSCT for the treatment of adult patients with Ph+ ALL. We searched the PubMed, Embase, Scopus, and Cochrane Library for studies published before June 2019 without language restriction. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS) and odds ratios (ORs) and 95% CIs for relapse rate (RR) and treatment-related mortality (TRM). Four prospective studies and one retrospective study were included with a total of 810 patients. We found auto-HSCT was superior to allo-HSCT in OS (HR = 1.42, 95% CI: 1.06-1.91, P = 0.02), and there was no difference between allo-HSCT and auto-HSCT for RFS (HR = 1.10, 95% CI: 0.86-1.40, P = 0.44) and RR (OR = 0.53, 95% CI: 0.22-1.26, P = 0.15). The risk of TRM for patients undergoing allo-HSCT was significantly higher than that of the patients who received auto-HSCT (OR = 5.06, 95% CI: 1.03-24.75, P = 0.05). Our meta-analysis shows that auto-HSCT may be an attractive and alternative treatment option for adult Ph+ ALL patients achieving CMR, with similar or better outcomes than allo-HSCT in the era of TKIs.
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Transplante de Células-Tronco Hematopoéticas , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Aloenxertos , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Taxa de SobrevidaRESUMO
The use of hypomethylating agents (HMAs) prior to hematopoietic stem cell transplantation (HSCT) in patients with myelodysplastic syndromes (MDS) was still controversial. Therefore, we sought to evaluate the impact of hypomethylation therapy before HSCT, with a special focus on long-term outcome. Databases, including PubMed, Embase Ovid, and the Cochrane Library, were searched for studies published up to 4 November 2018. Overall survival (OS) was selected as the primary endpoint, and relapse-free survival (RFS) was the secondary endpoint. A total of 6 cohort studies were included in the final meta-analysis. Our results showed that the outcome of patients with MDS using HMAs prior to HSCT was similar compared to those who did not with OS (HR = 0.81, 95% CI 0.63-1.04, p = 0.104) and RFS (HR = 0.96, 95% CI 0.72-1.26, p = 0.749). The pooled HR of OS in the older patients was 0.75 (95% CI 0.57-0.98, p = 0.035). No evidence showed that patients with MDS will benefit from using HMAs before HSCT in long-term survival (OS and RFS) compared to chemotherapy or best supportive therapy, though older patients were more likely to benefit from pre-transplantation HMAs treatment in terms of long-term survival. Our conclusions await further validation by prospective studies with larger sample size and randomized-controlled design. Particularly, to clarify whether the older patients who are candidates for HSCT could benefit from this bridging treatment will be of great interest.
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Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Metilação de DNA/efeitos dos fármacos , Decitabina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/tratamento farmacológico , Aloenxertos , Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/farmacologia , Decitabina/farmacologia , Intervalo Livre de Doença , Humanos , Síndromes Mielodisplásicas/terapia , Pré-Medicação , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) genes are frequently altered in acute lymphoblastic leukaemia (ALL) patients. The aim of this meta-analysis was to comprehensively assess the prognostic value of CDKN2A/B deletions in ALL patients. METHODS: Systematic literature review was conducted in PubMed, Embase and Cochrane databases up to July 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. RESULTS: A total of thirteen studies including 2857 patients were eligible for this meta-analysis. Combined HRs suggested that CDKN2A/B deletions were poor prognostic factors for both overall survival (OS) (HR = 2.15, 95% CI 1.82-2.54) and event-free survival (EFS)/disease-free survival (DFS)/relapse-free survival (RFS) (HR = 2.16, 95% CI 1.73-2.69). The adverse impact remained significant in both adult and paediatric ALL patients, and also in subgroups by ethnicity, ALL type, detection method of CDKN2A/B deletions, statistical method and endpoint. CONCLUSIONS: Our findings suggested that CDKN2A/B deletions were associated with poor prognosis independently in both adult and childhood ALL patients. Inclusion of CDKN2A/B status may further improve the risk stratification of ALL patients. Key Messages Although numerous studies have explored the prognostic significance of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions in acute lymphoblastic leukaemia (ALL) patients, the results remain conflicting. In this meta-analysis, we found that CDKN2A/B deletions were independent poor prognostic markers for both adult and paediatric ALL patients. Our findings justify the inclusion of CDKN2A/B status in the risk stratification of ALL patients.
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Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Intervalo Livre de Doença , Feminino , Deleção de Genes , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
We retrospectively analyzed the samples collected from 66 patients with Ph+ALL enrolled on ChiCTR-TNRC-09000309 clinical trial. CR rate was 95.5%, and estimated 2-year OS and DFS were 51.7 ± 11.7% and 26.9 ± 11.6%, 3-year OS and DFS were 31.6 ± 12.0% and 23.4 ± 11.6%. By combining IKZF1 deletion and early molecular responses, we redefined the patients as low, intermediate, and high risk 3 groups separately. Patients with double negative in IKZF1 and early molecular response experienced significant superior survival, while patients with double positive would have the worst outcome, and patients who were one or the other with IKZF1 deletion or MRD status had intermediate outcome. Significant differences were found among 3 groups in regard to both OS (p < .001) and DFS (p < .001). Our findings suggest that Ph+ALL is a heterogeneous group of diseases with significantly different prognosis. Combination of IKZF1 deletion and MRD status enable better risk stratification of patients for assignment to optimal therapeutic strategies.
Assuntos
Fator de Transcrição Ikaros/genética , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Deleção de Sequência , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
Philadelphia chromosome with de novo acute myeloid leukemia (Ph + AML) arising from t(9;22) is an uncommon occurrence. Ph + AML is known to respond poorly to conventional chemotherapy. To the best of our knowledge, simultaneous diagnosis of de novo Ph + AML and lymphoma in a single patient has not yet been reported. The present study reports the case of a 37-year-old female patient who presented with bone pain, fever and lymphadenopathy, and was diagnosed as Ph + AML with concurrent diffuse large B cell lymphoma. Combined chemotherapy regimen covering AML and lymphoma was administered, achieving short-term response. However, the therapy soon failed and the patient succumbed to the disease. The present study reports the first case of Ph + AML occurring concurrently with diffuse large B cell lymphoma, and discusses certain differences between Ph + AML and chronic myelogenous leukemia in the myeloid blast crisis phase, as well as the appropriate therapeutic modalities for Ph + AML. In addition, the potential association between Ph + AML and diffuse large B cell lymphoma in this patient was investigated.