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1.
Artigo em Inglês | MEDLINE | ID: mdl-38839449

RESUMO

Breast implant insertion for breast reconstruction or breast augmentation is a developing procedure, with high demand worldwide-being the second most common plastic surgery in the US as of 2022. Breast-implant-associated anaplastic large cell lymphoma (BIA-ALCL) is T-cell, non-Hodgkin lymphoma, typically CD30+, ALK-, presenting with fluid collection in the inner aspect of the peri-implant capsule in most patients, with the onset exceeding 1-year after implantation. The mean time between breast implant insertion and BIA-ALCL development is 7-10 years. The main risk factor is the use of textured implants because of their susceptibility to triggering local inflammation and immune stimulation finally leading to lymphoproliferation. Genetic predispositions to hereditary breast cancer increase the risk of disease development as well. BIA-ALCL seems to be underestimated in many countries and the initial symptom-seroma might be overlooked and misdiagnosed. Despite its rarity, the awareness of the disease should be improved among patients and medical professionals. This paper summarizes epidemiology, etiopathogenesis, differential diagnosis, and treatment-both surgical and hematological approaches.

2.
Heart Lung Circ ; 33(5): 675-683, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38616466

RESUMO

BACKGROUND: Arterial hypertension is mentioned as a risk factor in cardio-oncology. This study aimed to assess the long-term prognostic value of arterial hypertension (AH) in diffuse large B-cell lymphoma (DLBCL). METHODS: We analysed data collected by the Polish Lymphoma Research Group for the evaluation of the outcomes associated with the use of first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone therapy in patients with DLBCL with coexisting AH. Patients with other cardiovascular comorbidities or premature chemotherapy discontinuation due to cardiovascular toxicity were excluded. RESULTS: Pre-existing AH was diagnosed in 65 of 232 patients with DLBCL (28%) included in the study, and was associated with significantly shorter overall survival values (p<0.00001). The rates of DLBCL recurrence, administration of second-, third-, or fourth-line chemotherapy, and lymphoma-related deaths were similar in patients with and those without AH. Cardiovascular deaths were significantly more frequently observed in patients with pre-existing AH (38.5% vs 3.6%, p<0.0001). In the univariate analysis, AH (p=0.000001), older age (p<0.000001), and diabetes (p=0.0065) were identified as significant predictors of all-cause mortality; however, cardiovascular mortality was associated with AH (p<0.000001), older age (p=0.000008), and dyslipidaemia (p=0.03). Multivariate analysis revealed AH as an age-independent significant predictor of all-cause (p=0.00045) and cardiovascular mortality (p<0.000001). CONCLUSION: In the long-term follow-up of patients with DLBCL, the role of AH, as an important age-independent predictor of premature cardiovascular mortality, was so strong that it may have value for use in close surveillance in cardio-oncology clinics.


Assuntos
Hipertensão , Linfoma Difuso de Grandes Células B , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Feminino , Polônia/epidemiologia , Pessoa de Meia-Idade , Idoso , Hipertensão/epidemiologia , Hipertensão/complicações , Taxa de Sobrevida/tendências , Prognóstico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Seguimentos , Fatores de Risco , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Vincristina/uso terapêutico , Ciclofosfamida/uso terapêutico , Rituximab/uso terapêutico , Rituximab/administração & dosagem
3.
J Clin Med ; 13(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38398301

RESUMO

Background: Acute myeloid leukemia post cytotoxic therapy (AML-pCT) among breast cancer (BC) survivors represents a life-threatening complication. This study aims to assess the clinical outcomes of AML-pCT post BC. Methods: An analysis of all AML patients treated at a single hematology center (2000-2023) was performed to select patients with AML-pCT post BC. We applied the 2022 ELN criteria to define the genetic risk. Results: Among 847 AML patients, 28 were diagnosed with AML-pCT following BC. Complex karyotype (CK) occurred in 23.8% of patients. The median overall survival (OS) was 40 months. The survival outcomes were better after allogenic hematopoietic stem cell transplantation (alloHCT) treatment compared to chemotherapy alone (median OS: 47 versus 7 months, p = 0.008). Patients demonstrating CK showed lower survival compared to those without CK (2-year OS: 25.0% versus 66.2%, p = 0.0048). The multivariable Cox proportional hazards regression model indicated that treatment with alloHCT emerged as a significant factor associated with improved OS. The treatment was associated with superior OS (HR = 0.07, 95% CI = 0.01-0.86, p = 0.04). Conclusions: Patients with AML-pCT following BC were characterized with the highest frequency of adverse genetic risk profiles and demonstrated worse survival rates. AlloHCT should be performed as early as possible in such patients. The growing need for studies on inherited cancer susceptibility underscores the importance of close AML-pCT development monitoring in BC survivors.

6.
Adv Clin Exp Med ; 32(1): 131-136, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36603138

RESUMO

BACKGROUND: The first-line obinutuzumab-based immunochemotherapy improves the outcome of patients with follicular lymphoma (FL) compared with rituximab-based regimens. However, infusion-related reactions occur in almost half of patients during the 1st obinutuzumab administration. OBJECTIVES: The study aimed to evaluate the early effectiveness and safety of obinutuzumab-based induction regimens in a real-world setting. MATERIAL AND METHODS: Outcomes of patients diagnosed with FL and treated with obinutuzumab between January 2020 and September 2021 were analyzed. RESULTS: The study group included 143 treatment-naïve patients with FL. The median age was 52 years (range: 28-89 years); 45.1% of patients had a high-risk disease as assessed using the Follicular Lymphoma International Prognostic Index (FLIPI). Induction chemotherapy included: O-CVP (obinutuzumab, cyclophosphamide, vincristine, prednisolone) in 49.0% of patients, O-CHOP (O-CVP plus doxorubicin) in 28.7% and O-BENDA (obinutuzumab, bendamustine) in 22.4%. Complete response (CR) and partial response (PR) rates were 69.9% and 26.5%, respectively. There was no difference in response rates between different regimens (p = 0.309). Maintenance was started in 115 patients (85.2%). In the 1st cycle, obinutuzumab was administered as a single 1000-milligram infusion in 47.9% of patients, whereas in 52.1%, initial infusions were split over 2 days (100 mg/900 mg). Infusion-related reactions were reported only during the 1st administration of obinutuzumab in 9.1% of patients, with a similar incidence in those receiving the total dose on a single day or split over 2 days (p = 0.458). The most common adverse events were hematological. Five patients died from coronavirus disease 2019 (COVID-19). CONCLUSION: The early responses to induction regimens and adverse events profile were similar for every type of induction treatment. The infusion-related reactions were rare and limited to the 1st dose of obinutuzumab.


Assuntos
COVID-19 , Linfoma Folicular , Humanos , Pessoa de Meia-Idade , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/etiologia , Linfoma Folicular/patologia , Rituximab/efeitos adversos , Estudos Retrospectivos , Polônia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina
8.
Pol Arch Intern Med ; 133(1)2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36165652

RESUMO

INTRODUCTION: Therapy­related acute myeloid leukemia (t­AML), a life­threatening complication of cytotoxic therapy, represents an emerging challenge of modern oncology. OBJECTIVES: We aimed to evaluate clinical outcomes of patients with t­AML, taking into consideration genetic changes and treatment intensity. PATIENTS AND METHODS: We conducted a retrospective analysis of all consecutive AML patients from a single hematology center (hospitalized between 2000 and 2021). The diagnosis of t­AML was established according to the 2016 World Health Organization criteria. Overall survival (OS) and progression­free survival (PFS) were used to evaluate treatment outcomes. Retrospective identification of 17p13 deletion and TP53 mutation was conducted. RESULTS: Among 743 patients with AML, 60 (8.1%) were diagnosed with t­AML (63.4% had previous solid tumors). A complex karyotype (CK) and 17p13 deletion were detected in 26.8% and 26.7% of the t­AML cases, respectively, while FLT3­ITD and TP53 mutations occurred in 15.4% and 12.5% of the patients with t­AML, respectively. Median OS and PFS were 13 and 8 months, respectively. The survival outcomes were superior in the patients who underwent an allogenic hematopoietic cell transplantation (alloHCT) than in those treated with intensive chemotherapy alone (median OS, 47 vs 7 months, respectively; P = 0.01). Patients with therapy­related acute promyelocytic leukemia did not reach the median OS, and worse survival was noted in CK than non­CK t­AML (median OS, 6 vs 24 months; P = 0.02). In intensively treated t­AML, the survival was better for the patients younger than 64 years (P = 0.03). In the multivariable Cox proportional hazards regression model, alloHCT was associated with longer OS (hazard ratio, 0.19; 95% CI, 0.04-0.91; P = 0.04). Moreover, we noted a high frequency of treatment­related complications of t­AML. CONCLUSIONS: Our study revealed that prognosis of t­AML varies. Hence, the treatment strategy should include performing alloHCT as soon as possible in the patients with an adverse genetic profile.


Assuntos
Leucemia Mieloide Aguda , Humanos , Estudos Retrospectivos , Leucemia Mieloide Aguda/genética , Resultado do Tratamento , Prognóstico , Modelos de Riscos Proporcionais , Deleção Cromossômica
9.
Clin Lymphoma Myeloma Leuk ; 22(6): 405-415, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34933827

RESUMO

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have greatly improved the treatment outcome for most patients with chronic myeloid leukemia (CML). Ponatinib is a new pan-inhibitor of TK active in resistant CML. This study aimed to evaluate the efficacy and safety of ponatinib in patients suffering from CML. PATIENTS AND METHODS: This multicenter, non-randomized, observational, retrospective study evaluated the efficacy and safety of ponatinib administered in adult CML patients in any disease phase, including those with a detected ABL T315I mutation, which were resistant or intolerant to previous-generation TKIs. The study comprised 43 patients benefiting from the ponatinib donation program who were treated in 16 Polish centers. RESULTS: For patients who started treatment with ponatinib in chronic phase (CP) (n = 23) and in accelerated phase (AP) (n = 3) the median time on ponatinib was 19.5 months (range: 1.0-35.4), and 31.7 months (range: 31.0-34.1), respectively. All these patients were in CP after 1 month of treatment and at the end of observation - none of them progressed to AP or blastic phase (BP) during the study, meaning that progression-free survival was 100% at the end of observation (35.4 months). The estimated 2-year survival in this group of patients was 84%. For all 43 patients, median survival was not reached (lower quartile 6.3 months), and estimated 2-year survival was 60%. CONCLUSION: Our analysis confirmed ponatinib efficacy in a significant proportion of patients heavily pre-treated with TKIs achieving durable responses in both CP and AP/BP CML groups.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Adulto , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Imidazóis , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Polônia , Inibidores de Proteínas Quinases/efeitos adversos , Piridazinas , Estudos Retrospectivos
10.
Acta Oncol ; 60(10): 1361-1368, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34346830

RESUMO

Introduction: Primary cutaneous indolent B-cell lymphomas (PCBCLs) are not well characterized due to their rarity and indolent character.Methods: We retrospectively reviewed the data from 52 patients with primary cutaneous follicular lymphoma (PCFL) (n = 26), marginal zone lymphoma (PCMZL) (n = 25) or undefined PCBCL (n = 1) treated in 10 hematology centers in 1999-2019.Results: Patients characteristics and diagnostic approach: In almost half of the patients, pruritus or pain were present at diagnosis. The lesions were predominantly located on the head and trunk. The disease was present in a form of solitary infiltration or disseminated lesions with a similar frequency.Treatment details and outcomes: Surgery, radiotherapy, rituximab alone or combined with chemotherapy were applied as first-line treatment in 33%, 25%, 21% and 21% of patients, with complete response (CR) achieved by 94%, 83%, 50% and 70% of patients, respectively (p = 0.28). The median duration of response (DoR) was 65 months (95%CI 35-155).Survival: After the median follow-up time of 46 months (range: 3-225), the estimated 5-year overall survival (OS) and progression-free survival (PFS) were 93% and 54%, respectively.Discussion: Clinical presentation was largely consistent with the literature data, however, we observed some differences, including higher predilection to affect upper extremities (25%) and more frequent multifocal appearance in PCFCL (64%) and unifocal in PCMZL (70%).A high proportion of patients with indolent PCBCL achieved CR after the first-line therapy (77%), regardless of treatment mode. We did not find any impact of clinical features on treatment outcomes.Conclusions: All treatment modalities resulted in a high overall response rate. Surgery and/or radiotherapy are the optimal therapeutic options for patients with localized disease. The decision to treat systemically should rather be limited to the generalized form of the disease. High response rate, long duration of remission and excellent long-term survival confirm the truly indolent character of PCFCL and PCMZL.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Linfoma Folicular , Neoplasias Cutâneas , Humanos , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma Folicular/terapia , Estudos Multicêntricos como Assunto , Estudos Retrospectivos , Rituximab , Neoplasias Cutâneas/terapia
11.
J Cell Mol Med ; 24(18): 10970-10977, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32794659

RESUMO

Sézary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) characterized by the presence of circulating malignant CD4+ T cells (Sézary cells) with many complex changes in the genome, transcriptome and epigenome. Epigenetic dysregulation seems to have an important role in the development and progression of SS as it was shown that SS cells are characterized by widespread changes in DNA methylation. In this study, we show that the transmembrane protein coding gene TMEM244 is ectopically expressed in all SS patients and SS-derived cell lines and, to a lower extent, in mycosis fungoides and in a fraction of T-cell lymphomas, but not in B-cell malignancies and mononuclear cells of healthy individuals. We show that in patient samples and in the T-cell lines TMEM244 expression is negatively correlated with the methylation level of its promoter. Furthermore, we demonstrate that TMEM244 expression can be activated in vitro by the CRISPR-dCas9-induced specific demethylation of TMEM244 promoter region. Since both, TMEM244 expression and its promoter demethylation, are not detected in normal lymphoid cells, they can be potentially used as markers in Sézary syndrome and some other T-cell lymphomas.


Assuntos
Metilação de DNA , Regulação da Expressão Gênica/genética , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Regiões Promotoras Genéticas/genética , Síndrome de Sézary/genética , Idoso , Idoso de 80 Anos ou mais , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Feminino , Vetores Genéticos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Humanos , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/metabolismo , Masculino , Proteínas de Membrana/biossíntese , Pessoa de Meia-Idade , Micose Fungoide/genética , Micose Fungoide/metabolismo , Proteínas de Neoplasias/biossíntese , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Síndrome de Sézary/metabolismo
12.
Sci Rep ; 10(1): 3517, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32103128

RESUMO

Comorbidities impair the prognosis of diffuse large B-cell lymphoma (DLBCL). Type 2 diabetes mellitus (DMT2) increases the risk of other comorbidities, e.g., heart failure (HF). Thus, we hypothesized that pre-existing DMT2 may negatively affect the outcome of DLBCL. To verify this, DLBCL patients treated with (R)-CHOP were enrolled. 469 patients were eligible, with a median age of 57 years; 356 patients had advanced-stage DLBCL. 126 patients had high-intermediate and 83 high-risk international prognostic index (IPI). Seventy-six patients had DMT2, 46 HF; 26 patients suffered from both DMT2 and HF. In the analyzed group DMT2 or HF significantly shortened overall survival (OS) and progression free survival (PFS): the 5-year OS for patients with DMT2 was 64% vs 79% and for those with HF: 49% vs 79%. The 5-year PFS for DMT2 was 50.6% vs 62.5% and for HF 39.4% vs 63.2%. The relapse/progression incidence was comparable between groups; the non-relapse/progression mortality (NRPM) was significantly higher solely in DMT2 patients (5-year NRPM 22.5% vs 8.4%). The risk of death was higher in patients with higher IPI (HR = 1.85) and with DMT2 (HR = 1.87). To conclude, pre-existing DMT2, in addition to a higher IPI and HF, was a negative predictor for OS and PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Diabetes Mellitus Tipo 2 , Linfoma Difuso de Grandes Células B , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/administração & dosagem
13.
Pol Arch Intern Med ; 127(6): 392-400, 2017 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-28546528

RESUMO

INTRODUCTION: In the era of implementing novel agents in multiple myeloma (MM) regimens, drug resistance has become a key factor undermining the results of treatment. Identifying biomarkers allows the prediction of therapy outcomes with specific agents and may lead to the avoidance of resistance. OBJECTIVES: This study aimed to identify biomarkers in the pretreatment sera of patients with refractory/ relapsed MM that differ from those in the sera of patients who achieved a better depth of response with bortezomib-containing therapy. PATIENTS AND METHODS: Pretreatment serum samples were obtained from 61 proteasome inhibitor-naive, transplant-eligible patients who were eligible for salvage PAD (bortezomib, doxorubicin, and dexamethasone) or VTD (bortezomib, thalidomide, and dexamethasone) chemotherapy. Based on their response to therapy, patients were classified into 3 groups: complete or very good partial response, partial response, and progressive or stable disease. A comparative proteomic analysis of the groups was performed. RESULTS: The analyzed groups significantly differed in terms of both overall survival and progression­free survival. In total, 632 proteins were identified. The proteomic signature revealed 54 proteins that differentiated each analyzed experimental group. Functional analysis revealed that the main identified pathways (17 proteins) involved the regulation of hydrolase activity and cellular response to stimuli. The identified proteins included apolipoprotein C1, complement components, and sulfhydryl oxidase 1. CONCLUSIONS: Our results demonstrated that the label-free proteomic analysis is a useful method for describing proteins differentially expressed in the sera of patients with MM. Further studies are needed to analyze the use of identified proteins as biomarkers.


Assuntos
Bortezomib/farmacologia , Mieloma Múltiplo/sangue , Proteoma/análise , Terapia de Salvação , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/sangue , Bortezomib/uso terapêutico , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Resultado do Tratamento
14.
Int J Cardiol ; 235: 147-153, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28268088

RESUMO

BACKGROUND: Algorithm of anthracycline-based chemotherapy with favourable cardio-oncological outcome should be clearly re-defined for lymphoma patients with significant pre-existing cardiovascular diseases. A clinical benefit of liposomal forms of anthracycline is still debatable. METHODS: Polish registry included observations of 138 lymphoma patients with concomitant cardiovascular disorders who received liposomal doxorubicin as cardioprotective alternative of conventional form. It was created to analyse the importance of a strategy of administration of conventional/liposomal doxorubicin and a lifetime doxorubicin dose for development of acute decompensated heart failure (ADHF) as a reason of premature chemotherapy discontinuation. RESULTS: ADHF was the cause of premature termination of chemotherapy only in 11 patients (7.97%). The five new episodes of ADHF related to liposomal doxorubicin were recorded in subgroup of 70 patients with pre-existing heart failure (7.14%). There was the similar incidence of ADHF when liposomal doxorubicin was applied after conventional form in dose 200mg/m2 or if earlier signs of iatrogenic myocardial damage was recognised: 5 cases in subgroup of 51 patients with baseline cardiovascular risk factors (9.8%). ADHF was observed in one of 17 patients (5.88%) receiving liposomal doxorubicin as second line chemotherapy after first line with conventional doxorubicin. Consequently throughout the study group ADHF didn't depend on the total cumulative dose of all types of doxorubicin: OR=0.85; 95%CI: 0.66-1.10; p=0.22 for each 50mg/m2. CONCLUSION: The schedule of administration of conventional/liposomal doxorubicin can decide that lifetime combined doses of anthracyclines become insignificant for ADHF occurrence and premature discontinuation of chemotherapy in lymphoma patients with pre-existing cardiovascular disturbances.


Assuntos
Doenças Cardiovasculares , Doxorrubicina/análogos & derivados , Insuficiência Cardíaca , Linfoma , Suspensão de Tratamento/estatística & dados numéricos , Doença Aguda , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Cardiotônicos/administração & dosagem , Cardiotônicos/efeitos adversos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Linfoma/complicações , Linfoma/tratamento farmacológico , Linfoma/epidemiologia , Masculino , Conduta do Tratamento Medicamentoso , Pessoa de Meia-Idade , Polônia/epidemiologia , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Sistema de Registros/estatística & dados numéricos
15.
J Clin Apher ; 32(6): 384-391, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28101890

RESUMO

Mobilized PBSC are the main source for allogeneic HSCT. We aimed to evaluate factors that affect CD34+ cell yield including the donor's age, gender, BSA, processed blood volume and the method of G-CSF dose calculation. Data from 170 healthy donors were analyzed. The concentration of CD34+ cells in the peripheral blood (PB) and the processed volume of blood were significantly correlated to CD34+ cells yield (P < .00005 and P < .001, respectively). The G-CSF dose per m2 was significantly correlated to the concentration of CD34+ cells in the PB (P = .0003) and in the product (P = .01). Smaller BSA and less processed volume were found among female donors, who were given lesser G-CSF dose per m2 , and showed lower yield compared to men. However, multivariate analysis of the yield showed that only the concentration of CD34+ cells in the PB and the processed volume remained independent significant.


Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco de Sangue Periférico/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Antígenos CD34/análise , Antígenos CD34/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico , Fatores Sexuais , Transplante Homólogo , Adulto Jovem
16.
Br J Haematol ; 175(5): 884-891, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27682187

RESUMO

We compared the outcomes of multiple myeloma (MM) patients aged 21-40 and 41-60 years in the novel agent era. This case-control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0·04) and high-risk cytogenetic abnormalities (83% vs. 68%; P = 0·007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P < 0·001). Five- and 10-year overall survival (OS) in younger versus older patients was 83% vs. 67% and 56% vs. 39%, respectively (P < 0·001). Similar results were seen when studying the subset of 780 patients who underwent autologous transplantation. Younger patients with ISS stage 1 had a better OS than older patients (P < 0·001). There was no survival difference between younger and older patients with ISS stage 2 or 3. Younger MM patients, aged 21-40 years, treated in the era of novel agents have a better OS than their counterparts aged 41-60 years, but the survival advantage observed in younger patients was lost in more advanced stages of MM.


Assuntos
Fatores Etários , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Adulto , Estudos de Casos e Controles , Aberrações Cromossômicas , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Estadiamento de Neoplasias , Taxa de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
17.
Oncotarget ; 7(35): 56726-56736, 2016 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-27527861

RESUMO

Identifying biomarkers of the resistance in multiple myeloma (MM) is a key research challenge. We aimed to identify proteins that differentiate plasma cells in patients with refractory/relapsed MM (RRMM) who achieved at least very good partial response (VGPR) and in those with reduced response to PAD chemotherapy (bortezomib, doxorubicin and dexamethasone). Comparative proteomic analysis was conducted on pretreatment plasma cells from 77 proteasome inhibitor naïve patients treated subsequently with PAD due to RRMM. To increase data confidence we used two independent proteomic platforms: isobaric Tags for Relative and Absolute Quantitation (iTRAQ) and label free (LF). Proteins were considered as differentially expressed when their accumulation between groups differed by at least 50% in iTRAQ and LF. The proteomic signature revealed 118 proteins (35 up-regulated and 83 down-regulated in ≥ VGPR group). Proteins were classified into four classes: (1) involved in proteasome function; (2) involved in the response to oxidative stress; (3) related to defense response; and (4) regulating the apoptotic process. We confirmed the differential expression of proteasome activator complex subunit 1 (PSME1) by enzyme-linked immunosorbent assay. Increased expression of proteasomes and proteins involved in protection from oxidative stress (eg., TXN, TXNDC5) plays a major role in bortezomib resistance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Recidiva Local de Neoplasia/metabolismo , Idoso , Antineoplásicos , Apoptose , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estresse Oxidativo , Proteômica , Espectrometria de Massas em Tandem , Tiorredoxinas/química , Resultado do Tratamento
18.
Onco Targets Ther ; 9: 2069-80, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27103833

RESUMO

BACKGROUND: The breast is a rare site of extranodal involvement of diffuse large B-cell lymphoma (DLBCL). We aimed to assess the clinical characteristics, prognostic factors, and treatment outcomes of breast DLBCL. PATIENTS AND METHODS: We retrospectively analyzed 113 patients (from our institution and the literature) between 1973 and 2014. The primary end point was overall survival (OS). Kaplan-Meier OS curves were compared with the log-rank test. Cox regression analysis was applied to determine the prognostic factors for OS, progression-free survival (PFS), local control (LC), and cause-specific survival (CSS). RESULTS: A total of 113 patients were included in the study: 42 cases from our hospital and 71 cases from 12 publications. The median age at diagnosis was 58 years. With a median follow-up time of 39.2 months, the estimated 5-year OS, PFS, LC, and CSS were 71.4%, 58.8%, 75.6%, and 74.9%, respectively. In multivariate analysis, more than four cycles of chemotherapy, having localized cancer, lumpectomy with or without axillary lymph node (ALN) dissection, and low to low-to-intermediate International Prognostic Index were favorable factors for OS. For PFS, significant prognostic factors were rituximab use, B symptoms, and tumor size. As for the local group, lumpectomy with or without ALN dissection and more than four cycles of chemotherapy were favorable factors for OS. Tumor size >4 cm and nonuse of rituximab were adverse factors for PFS. Twenty-one patients (18.6%) developed local relapse and 33 (29.2%) developed systemic relapse. Eight patients had central nervous system relapse (7.3%). CONCLUSION: Our results reveal that local and extended staging criteria can reflect the different prognosis and treatment outcomes of breast DLBCL. Rituximab use, lumpectomy, and more than four cycles of chemotherapy are recommended as a treatment regimen. However, further study is warranted to validate our data.

19.
Pol Arch Med Wewn ; 125(10): 741-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26334344

RESUMO

INTRODUCTION: R-CHOP immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is a standard first-line treatment for diffuse large B-cell lymphoma (DLBCL). None of the randomized trials have proved a statistically significant overall survival (OS) benefit in high-risk subgroups according to the International Prognostic Index (IPI). OBJECTIVES: We retrospectively investigated the role of adding rituximab to anthracycline-based chemotherapy in patients with high-risk DLBCL according to the IPI. PATIENTS AND METHODS: A total of 371 patients with high-risk DLBCL treated at 15 Polish hematology centers were retrospectively analyzed in 2 distinct age groups: older than 60 years and 60 years old or younger. Response rates, OS, and progression-free survival (PFS) were compared and analyzed. RESULTS: The overall response rate (ORR) of high-risk DLBCL patients significantly improved in rituximabtreated patients compared with patients treated without rituximab (76.7% vs 95.6%; P <0.05). The R-CHOP immunochemotherapy prolonged survival in both older and younger subgroups. The 5-year projected OS and PFS in younger patients treated with rituximab vs chemotherapy alone were 42% vs 38% and 46% vs 27%, respectively (P <0.05), while the 5-year projected OS and PFS in older patients treated with rituximab vs chemotherapy alone were 82% vs 52% and 67% vs 45%, respectively (P <0.05). CONCLUSIONS: With all the limitations of a retrospective analysis, the superiority of adding rituximab to CHOP combination chemotherapy has been clearly demonstrated regarding ORR, OS, and PFS in both age subgroups of patients with high-risk DLBCL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Prednisona/uso terapêutico , Estudos Retrospectivos , Vincristina/uso terapêutico , Adulto Jovem
20.
Eur J Haematol ; 94(2): 109-14, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25039659

RESUMO

Novel agents including immunomodulatory drugs and proteasome inhibitors incorporated into induction regimens and subsequently followed by autologous stem cell transplantation in cases of multiple myeloma have resulted in enhancement of response rate and its depth. Maintaining or even improving the response is an important treatment goal. Most clinical trials have revealed increased progression-free survival after consolidation and maintenance therapy. Some of them have also shown prolongation of overall survival. However, continuous therapy may be associated with significant side effects and costs, and therefore remains controversial. Treatment decisions should be individualized and based upon projected benefits and risks.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Consolidação , Quimioterapia de Manutenção , Mieloma Múltiplo/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Bortezomib , Transplante de Células-Tronco Hematopoéticas , Humanos , Mieloma Múltiplo/terapia , Segunda Neoplasia Primária/etiologia , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Transplante Autólogo , Resultado do Tratamento
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