RESUMEN
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.
RESUMEN
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.
Asunto(s)
Hipertensión , Linfoma de Células B Grandes Difuso , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Femenino , Polonia/epidemiología , Persona de Mediana Edad , Anciano , Hipertensión/epidemiología , Hipertensión/complicaciones , Tasa de Supervivencia/tendencias , Pronóstico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Seguimiento , Factores de Riesgo , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Vincristina/uso terapéutico , Ciclofosfamida/uso terapéutico , Rituximab/uso terapéutico , Rituximab/administración & dosificaciónRESUMEN
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.
Asunto(s)
Hemofilia A , Hepatitis C , Humanos , Hepacivirus , Hemofilia A/terapia , Prevalencia , Polonia/epidemiologíaRESUMEN
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.
Asunto(s)
COVID-19 , Linfoma Folicular , Humanos , Persona de Mediana Edad , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/etiología , Linfoma Folicular/patología , Rituximab/efectos adversos , Estudios Retrospectivos , Polonia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/uso terapéutico , DoxorrubicinaAsunto(s)
Dermatitis Exfoliativa , Proteínas de la Membrana , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Dermatitis Exfoliativa/diagnóstico , Dermatitis Exfoliativa/genética , Expresión Génica , Micosis Fungoide/diagnóstico , Micosis Fungoide/genética , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Proteínas de la Membrana/genéticaRESUMEN
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.
Asunto(s)
Leucemia Mieloide Aguda , Humanos , Estudios Retrospectivos , Leucemia Mieloide Aguda/genética , Resultado del Tratamiento , Pronóstico , Modelos de Riesgos Proporcionales , Deleción CromosómicaRESUMEN
The [18F]FDG PET/CT is a crucial tool in the diagnostic process and monitoring of neoplastic diseases. Currently, during the global program of vaccination against COVID-19 and the possibility of axillary lymphadenopathy after this injection, the correct interpretation of PET/CT images is vitally significant and may create some difficulties. We present a case of increased uptake of [18F]FDG in an axillary lymph node in a PET/CT scan performed 2 days after the Pfizer BioNTech COVID-19 vaccine in a 48-year-old patient newly diagnosed with marginal zone B-cell lymphoma.
RESUMEN
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.
Asunto(s)
Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva , Adulto , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos , Humanos , Imidazoles , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Polonia , Inhibidores de Proteínas Quinasas/efectos adversos , Piridazinas , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Linfoma de Células B de la Zona Marginal , Linfoma Folicular , Neoplasias Cutáneas , Humanos , Linfoma de Células B de la Zona Marginal/terapia , Linfoma Folicular/terapia , Estudios Multicéntricos como Asunto , Estudios Retrospectivos , Rituximab , Neoplasias Cutáneas/terapiaRESUMEN
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.
Asunto(s)
Metilación de ADN , Regulación de la Expresión Génica/genética , Proteínas de la Membrana/genética , Proteínas de Neoplasias/genética , Regiones Promotoras Genéticas/genética , Síndrome de Sézary/genética , Anciano , Anciano de 80 o más Años , Sistemas CRISPR-Cas , Línea Celular Tumoral , Femenino , Vectores Genéticos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Humanos , Linfoma no Hodgkin/genética , Linfoma no Hodgkin/metabolismo , Masculino , Proteínas de la Membrana/biosíntesis , Persona de Mediana Edad , Micosis Fungoide/genética , Micosis Fungoide/metabolismo , Proteínas de Neoplasias/biosíntesis , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Síndrome de Sézary/metabolismoRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Diabetes Mellitus Tipo 2 , Linfoma de Células B Grandes Difuso , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ciclofosfamida/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/mortalidad , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Rituximab/administración & dosificación , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
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.
Asunto(s)
Bortezomib/farmacología , Mieloma Múltiple/sangre , Proteoma/análisis , Terapia Recuperativa , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores/sangre , Bortezomib/uso terapéutico , Dexametasona/farmacología , Dexametasona/uso terapéutico , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Humanos , Mieloma Múltiple/tratamiento farmacológico , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Enfermedades Cardiovasculares , Doxorrubicina/análogos & derivados , Insuficiencia Cardíaca , Linfoma , Privación de Tratamiento/estadística & datos numéricos , Enfermedad Aguda , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Cardiotónicos/administración & dosificación , Cardiotónicos/efectos adversos , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/diagnóstico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Linfoma/complicaciones , Linfoma/tratamiento farmacológico , Linfoma/epidemiología , Masculino , Administración del Tratamiento Farmacológico , Persona de Mediana Edad , Polonia/epidemiología , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Sistema de Registros/estadística & datos numéricosRESUMEN
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.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre de Sangre Periférica/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Antígenos CD34/análisis , Antígenos CD34/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Células Madre de Sangre Periférica , Factores Sexuales , Trasplante Homólogo , Adulto JovenRESUMEN
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.
Asunto(s)
Factores de Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Adulto , Estudios de Casos y Controles , Aberraciones Cromosómicas , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Estadificación de Neoplasias , Tasa de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Resistencia a Antineoplásicos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Anciano , Antineoplásicos , Apoptosis , Bortezomib/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Estrés Oxidativo , Proteómica , Espectrometría de Masas en Tándem , Tiorredoxinas/química , Resultado del TratamientoRESUMEN
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.
RESUMEN
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.