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Warming of the ocean waters surrounding Greenland plays a major role in driving glacier retreat and the contribution of glaciers to sea level rise. The melt rate at the junction of the ocean with grounded ice-or grounding line-is, however, not well known. Here, we employ a time series of satellite radar interferometry data from the German TanDEM-X mission, the Italian COSMO-SkyMed constellation, and the Finnish ICEYE constellation to document the grounding line migration and basal melt rates of Petermann Glacier, a major marine-based glacier of Northwest Greenland. We find that the grounding line migrates at tidal frequencies over a kilometer-wide (2 to 6 km) grounding zone, which is one order of magnitude larger than expected for grounding lines on a rigid bed. The highest ice shelf melt rates are recorded within the grounding zone with values from 60 ± 13 to 80 ± 15 m/y along laterally confined channels. As the grounding line retreated by 3.8 km in 2016 to 2022, it carved a cavity about 204 m in height where melt rates increased from 40 ± 11 m/y in 2016 to 2019 to 60 ± 15 m/y in 2020 to 2021. In 2022, the cavity remained open during the entire tidal cycle. Such high melt rates concentrated in kilometer-wide grounding zones contrast with the traditional plume model of grounding line melt which predicts zero melt. High rates of simulated basal melting in grounded glacier ice in numerical models will increase the glacier sensitivity to ocean warming and potentially double projections of sea level rise.
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OBJECTIVE: The search for other indicators to assess the weight and nutritional status of individuals is important as it may provide more accurate information and assist in personalized medicine. This work is aimed to develop a machine learning predictions of weigh status derived from bioimpedance measurements and other physical parameters of healthy younger volunteers from Southern Cuba Region. METHODS: A pilot random study at the Pediatrics Hospital was conducted. The volunteers were selected between 2002 and 2008, ranging in age between 2 and 18 years old. In total, 776 female and male volunteers are studied. Along the age and sex in the cohort, volunteers with class I obesity, overweight, underweight and with normal weight are considered. The bioimpedance parameters are obtained by measuring standard tetrapolar whole-body configuration. The bioimpedance analyser is used, collecting fundamental bioelectrical and other parameters of interest. A classification model are performed, followed by a prediction of the body mass index. RESULTS: The results derived from the classification leaner reveal that the size, body density, phase angle, body mass index, fat-free mass, total body water volume according to Kotler, body surface area, extracellular water according to Kotler and sex largely govern the weight status of this population. In particular, the regression model shows that other bioparameters derived from impedance measurements can be associated with weight status estimation with high accuracy. CONCLUSION: The classification and regression predictive models developed in this work are of the great importance to assist the diagnosis of weigh status with high accuracy. These models can be used for prompt weight status evaluation of younger individuals at the Pediatrics Hospital in Santiago de Cuba, Cuba.
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Índice de Masa Corporal , Peso Corporal , Impedancia Eléctrica , Humanos , Masculino , Cuba , Femenino , Niño , Adolescente , Preescolar , Proyectos Piloto , Aprendizaje Automático , Composición Corporal , Estado Nutricional , Delgadez/diagnóstico , Análisis de RegresiónRESUMEN
OBJECTIVE: The search for other indicators to assess the weight status of individuals is important as it may provide more accurate information and assist in personalized medicine.This work is aimed to develop a machine learning predictions of weigh status derived from bioimpedance measurements and other physical parameters of healthy infant juvenile cohort from the Southern Cuba Region, Santiago de Cuba. METHODS: The volunteers were selected between 2002 and 2008, ranging in age between 2 and 18 years old. In total, 393 female and male infant and juvenile individuals are studied. The bioimpedance parameters are obtained by measuring standard tetrapolar whole-body configuration. A classification model are performed, followed by a prediction of other bioparameters influencing the weight status. RESULTS: The results obtained from the classification model indicate that fat-free mass, reactance, and corrected resistance primarily influence the weight status of the studied population. Specifically, the regression model demonstrates that other bioparameters derived from impedance measurements can be highly accurate in estimating weight status. CONCLUSION: The classification and regression predictive models developed in this work are of the great importance for accessing to the weigh status with high accuracy of younger individuals at the Oncological Hospital in Santiago de Cuba, Cuba.
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Peso Corporal , Impedancia Eléctrica , Aprendizaje Automático , Humanos , Cuba , Masculino , Femenino , Adolescente , Preescolar , Niño , Composición Corporal , Lactante , Estudios de CohortesRESUMEN
Melphalan (M), in combination with prednisone (MP), has been the backbone of new combinations, including bortezomib plus MP (VMP). However, new alkylator-free schemes, such as lenalidomide plus low-dose dexamethasone, are challenging the role of alkylators in myeloma treatment of elderly patients. Here we have updated, after a long follow-up (median 6 years), the results of the GEM2005 study that addressed this question by comparing VMP with bortezomib plus thalidomide and prednisone (VTP) as induction. Between April 2005 and October 2008, 260 patients were randomized to receive 6 cycles of VMP or VTP as induction. The median progression-free survival was 32 months for the VMP and 23 months for the VTP arms (P 5 .09). VMP significantly prolonged the overall survival (OS) compared with VTP (median of 63 and 43 months, respectively; hazard ratio [HR]: 0.67, P 5 .01). Achieving immunophenotypic complete response was associated with a significantly longer OS, especially in the VMP arm (66%remain alive after 8 years). Melphalan, plus bortezomib, should be maintained as standard care for the treatment of elderly multiple myeloma patients. This trial was registered at www.clinicaltrials.gov as #NCT00443235.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Anciano , Ácidos Borónicos/administración & dosificación , Bortezomib , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción , Estimación de Kaplan-Meier , Quimioterapia de Mantención , Masculino , Melfalán/administración & dosificación , Prednisona/administración & dosificación , Pirazinas/administración & dosificación , Talidomida/administración & dosificaciónRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease influenced by genetic and environmental factors. The role of the HLA system in tumor antigen presentation could be involved in susceptibility and disease control. We analyzed the phenotypic frequencies of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 in 250 DLBCLs, comparing them with 1940 healthy individuals. We also evaluated the influence of HLA polymorphisms on survival in those patients treated with curative intention using cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)-like regimen without (n = 64, 26%) or with (n = 153, 61%) rituximab. DLBCL patients have a higher phenotypic frequency of HLA-DRB1*01 (29% vs 19.5%, P = .0008, Pc = .0104) and a lower frequency of HLA-C*03 (6.4% vs 17.9%, P < .0005, Pc = .007) compared with healthy individuals. Irrespective of the age-adjusted International Prognostic Index, those patients receiving a CHOP-like plus rituximab regimen and carrying the HLA-B44 supertype had worse 5-year progression-free (54% vs 71%, P = .019) and 5-year overall (71% vs 92%, P = .001) survival compared with patients without this supertype. Our data suggest that some HLA polymorphisms influence the development and outcome of DLBCL, allowing the identification of an extremely good-risk prognostic subgroup. However, these results are preliminary and need to be validated in order to exclude a possible population effect.
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Antígenos HLA/genética , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Casos y Controles , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Frecuencia de los Genes , Cadenas HLA-DRB1/genética , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo Genético , Prednisolona/uso terapéutico , Pronóstico , Factores de Riesgo , Rituximab , Vincristina/uso terapéutico , Adulto JovenRESUMEN
We conducted a multicentre, phase II study of interim positron emission tomography (PET) as a guide to risk-adapted therapy in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients achieving negative fluorodeoxyglucose (FDG)-PET after three courses of R-MegaCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) received three additional courses, whereas PET-positive patients received two courses of R-IFE (rituximab, ifosfamide, etoposide) followed by BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem-cell transplantation. The primary endpoint was progression-free survival (PFS). 71 patients (median age 55 years, range 25-69) were enrolled. With a median follow-up of 42·8 months (range 7·2-58·4), the estimated 4-year PFS and overall survival (OS) were 67% and 78%, respectively, for the global series. Patients in complete remission after interim PET (N = 36) had significantly better 3-year PFS than those with partial response (N = 30) [81% vs. 57%, Hazard ratio (HR) = 2·6, 95% confidence interval (CI) = 1·02-6·65] but not a statistically significant longer OS. A retrospective PET central review was done for 51 patients. According to semiquantitative analysis, 3-year PFS (81% vs. 33%; HR = 6·9, 95% CI = 2·35-20·6) and OS (95% vs. 33%, HR = 19·4, 95% CI = 3·89-97·0) were significantly better for negative than for positive interim PET patients. Early PET assessment is valuable for risk stratification in DLBCL; for this purpose semiquantitative evaluation is a better predictor than visual criteria.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Radioisótopos de Flúor , Fluorodesoxiglucosa F18 , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Tomografía de Emisión de Positrones , Radiofármacos , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carmustina/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/terapia , Masculino , Melfalán/administración & dosificación , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica , Prednisona/administración & dosificación , Pronóstico , Estudios Prospectivos , Inducción de Remisión , Rituximab , Trasplante Autólogo , Resultado del Tratamiento , Vincristina/administración & dosificaciónAsunto(s)
Clorhidrato de Bendamustina/uso terapéutico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Rituximab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Linfoma de Células B de la Zona Marginal/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
Maintenance therapy has become a hot field in myeloma, and it may be particularly relevant in elderly patients because the major benefit results from the initial therapy. We report the results of a randomized comparison of maintenance with bortezomib plus thalidomide (VT) or prednisone (VP) in 178 elderly untreated myeloma patients who had received 6 induction cycles with bortezomib plus either melphalan and prednisone or thalidomide and prednisone. The complete response (CR) rate increased from 24% after induction up to 42%, higher for VT versus VP (46% vs 39%). Median progression-free survival (PFS) was superior for VT (39 months) compared with VP (32 months) and overall survival (OS) was also longer in VT patients compared with VP (5-year OS of 69% and 50%, respectively) but the differences did not reach statistical significance. CR achievement was associated with a significantly longer PFS (P < .001) and 5-year OS (P < .001). The incidence of G3-4 peripheral neuropathy was 9% for VT and 3% for VP. Unfortunately, this approach was not able to overcome the adverse prognosis of cytogenetic abnormalities. In summary, these maintenance regimens result in a significant increase in CR rate, remarkably long PFS, and acceptable toxicity profile. The trial is registered at www.clinicaltrials.gov as NCT00443235.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Mantención , Mieloma Múltiple/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Ácidos Borónicos/administración & dosificación , Bortezomib , Aberraciones Cromosómicas , Femenino , Estudios de Seguimiento , Humanos , Hibridación Fluorescente in Situ , Masculino , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Prednisona/administración & dosificación , Pronóstico , Pirazinas/administración & dosificación , Inducción de Remisión , Tasa de Supervivencia , Talidomida/administración & dosificaciónRESUMEN
BACKGROUND: Bortezomib plus melphalan and prednisone (VMP) is significantly better than melphalan plus prednisone alone for elderly patients with untreated multiple myeloma; however, toxic effects are high. We investigated a novel and less intensive bortezomib-based regimen to maintain efficacy and to reduce toxic effects. METHODS: Between March, 2006, and October, 2008, 260 patients with untreated multiple myeloma, 65 years and older, from 63 Spanish centres, were randomly assigned to receive six cycles of VMP (n=130) or bortezomib plus thalidomide and prednisone (VTP; n=130) as induction therapy, consisting of one cycle of bortezomib twice per week for 6 weeks (1·3 mg/m² on days 1, 4, 8, 11, 22, 25, 29, and 32), plus either melphalan (9 mg/m² on days 1-4) or daily thalidomide (100 mg), and prednisone (60 mg/m² on days 1-4). The first cycle was followed by five cycles of bortezomib once per week for 5 weeks (1·3 mg/m² on days 1, 8, 15, and 22) plus the same doses of melphalan plus prednisone and thalidomide plus prednisone. 178 patients completed the six induction cycles and were randomly assigned to maintenance therapy with bortezomib plus prednisone (n=87) or bortezomib plus thalidomide (n=91), consisting of one conventional cycle of bortezomib for 3 weeks (1·3 mg/m² on days 1, 4, 8, and 11) every 3 months, plus either prednisone (50 mg every other day) or thalidomide (50 mg per day), for up to 3 years. Treatment codes were generated with a computerised random number generator, and neither participants nor study personnel were masked to treatment. The primary endpoint was response rate in induction and maintenance phases. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00443235. FINDINGS: In the induction phase, 105 (81%) patients in the VTP group and 104 (80%) in the VMP group achieved partial responses or better (p=0·9), including 36 (28%) and 26 (20%) complete remissions, respectively (p=0·2). Treatment with VTP resulted in more serious adverse events (40 [31%] vs 20 [15%], p=0·01) and discontinuations (22 [17%] vs 15 [12%], p=0·03) than did treatment with VMP. The most common toxicities (grade 3 or worse) were infections (one [1%] in the VTP group vs nine [7%] in the VMP group), cardiac events (11 [8%] vs 0), and peripheral neuropathy (nine [7%] vs 12 [9%]). After maintenance therapy, the complete remission rate was 42% (40 [44%] patients in complete remission in the bortezomib plus thalidomide group, 34 [39%] in the bortezomib plus prednisone group). No grade 3 or worse haematological toxicities were recorded during maintenance therapy; two (2%) patients in the bortezomib plus prednisone group and six (7%) in the bortezomib plus thalidomide group developed peripheral neuropathy. INTERPRETATION: Reduced-intensity induction with a bortezomib-based regimen, followed by maintenance, is a safe and effective treatment for elderly patients with multiple myeloma. FUNDING: Pethema (Spanish Program for the Treatment of Hematologic Diseases).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Factores de Edad , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/administración & dosificación , Bortezomib , Esquema de Medicación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Melfalán/administración & dosificación , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Prednisona/administración & dosificación , Modelos de Riesgos Proporcionales , Inhibidores de Proteasas/administración & dosificación , Pirazinas/administración & dosificación , Medición de Riesgo , Factores de Riesgo , España , Talidomida/administración & dosificación , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Ibrutinib demonstrated remarkable efficacy and favorable tolerability in patients with untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including those with high-risk genetic alterations. The IBRORS-CLL study assessed the characteristics, clinical management and outcome of CLL patients receiving ibrutinib in routine clinical practice in Spain. PATIENTS: Observational, retrospective, multicenter study in CLL patients who started single-agent ibrutinib as first-line treatment or at first or second relapse between January 2016 and January 2019. RESULTS: A total of 269 patients were included (median age: 70.9 years; cardiovascular comorbidity: 55.4%, including hypertension [47.6%] and atrial fibrillation [AF] [7.1%]). Overall, 96.7% and 69% of patients underwent molecular testing for del(17p)/TP53 mutation and IGHV mutation status. High-risk genetic features included unmutated IGHV (79%) and del(17p)/TP53 mutation (first-line: 66.3%; second-line: 23.1%). Overall, 84 (31.2%) patients received ibrutinib as first-line treatment, and it was used as second- and third-line therapy in 121 (45.0%) and 64 (23.8%) patients. The median progression-free survival and overall survival were not reached irrespective of del(17p)/TP53, or unmutated IGHV. Common grade ≥3 adverse events were infections (12.2%) and bleeding (3%). Grade ≥3 AF occurred in 1.5% of patients. CONCLUSION: This real-world study shows that single-agent ibrutinib is an effective therapy for CLL, regardless of age and high-risk molecular features, consistent with clinical trials. Additionally, single-agent ibrutinib was well tolerated, with a low rate of cardiovascular events. This study also emphasized a high molecular testing rate of del(17p)/TP53 mutation and IGHV mutation status in clinical practice according to guideline recommendations.
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Leucemia Linfocítica Crónica de Células B , Adenina/análogos & derivados , Anciano , Humanos , Piperidinas , Pirazoles/efectos adversos , Pirimidinas/efectos adversos , Estudios Retrospectivos , España/epidemiologíaRESUMEN
We report the characteristics of relapse, treatment response, and outcomes of 145 elderly patients with multiple myeloma in first relapse after front-line treatment with VMP or VTP. Reappearance of CRAB symptoms (113 patients) and more aggressive forms of disease (32 patients) were the most common patterns of relapse. After second-line therapy, 75 (51.7%) patients achieved at partial response and 16 (11%) complete response (CR). Overall survival was longer among patients receiving VMP as front-line induction (21.4 vs. 14.4 months, P=0.037), in patients achieving CR (28.3 vs. 14.8 months; P=0.04), and in patients without aggressive relapse (28.6 vs. 7.6 months; P=0.0007).
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BACKGROUND: No standard first-line systemic treatment for mucosa-associated lymphoid tissue (MALT) lymphoma is available. In a phase 2 study we aimed to assess the safety and activity of a response-adapted combination of bendamustine plus rituximab as upfront treatment for this type of lymphoma. METHODS: In a multicentre, single-arm, non-randomised, phase 2 trial, we enrolled patients with MALT lymphoma at any site and stage and treated them with bendamustine (90 mg/m(2) on days 1 and 2) plus rituximab (375 mg/m(2) on day 1), every 4 weeks. Inclusion criteria were measurable or evaluable disease, age 18-85 years, and unequivocal active lymphoma; we also enrolled patients with MALT lymphoma arising in the stomach after failure of Helicobacter pylori eradication and primary cutaneous cases after failure of local therapies. Exclusion criteria included evidence of histological transformation, CNS involvement, and active hepatitis B or C virus or HIV infection. After three cycles, patients achieving complete response received one additional cycle (total four cycles) and those achieving partial response received three additional cycles (total six cycles). The primary endpoint was 2-year event-free survival. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01015248. FINDINGS: 60 patients from 19 centres in Spain were enrolled between May 27, 2009, and May 23, 2011, and received treatment; 57 patients were evaluable for the primary endpoint. Only 14 (25%) patients needed more than four cycles of treatment. After a median follow-up of 43 months (IQR 37-51), median event-free survival was not reached. Event-free survival at 2 years was 93% (95% CI 84-97) and at 4 years was 88% (95% CI 74-95). The most frequently observed grade 3-4 adverse events were haematological: lymphopenia in 20 (33%) patients, neutropenia in 12 (20%) patients, and leucopenia in three (5%) patients. Grade 3-4 febrile neutropenia or infections were reported in three (5%) and four (7%) patients, respectively. INTERPRETATION: This response-adapted schedule of bendamustine plus rituximab appears to be an active and well tolerated first-line treatment for patients with MALT lymphoma. FUNDING: Grupo Español de Linfomas/Trasplante de Médula Ósea (GELTAMO), Mundipharma Spain, and Roche Pharma Spain.
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Veno-occlusive disease of the liver (VOD) is a potentially severe complication of high-dose cytoreductive therapy (HDT) used for stem cell transplantation (SCT). This complication is uncommon after HDT for autologous SCT (ASCT) in patients with multiple myeloma (MM). The Spanish Myeloma Group/PETHEMA conducted a study (MM2000) for patients with newly diagnosed MM consisting of induction with alternating VBMCP/VBAD chemotherapy followed by intensification with busulfan/melphalan (Bu/MEL) with a second high-dose therapy procedure in patients not achieving at least near-complete remission with the first procedure. After 2 years of the trial, a number of episodes resembling classical VOD but with a late onset were recognized. Consequently, the protocol was modified, and Bu/MEL was replaced by melphalan 200 mg/m(2) (MEL-200). Three years later, after a total of 734 patients had undergone first autologous SCT, the incidence and characteristics of VOD episodes were analyzed in the whole series. Nineteen cases of VOD (8%) were observed among the first 240 patients receiving Bu/MEL, whereas only 2 (0.4%) were observed among the 494 patients treated with MEL-200 (P < .0001). VOD manifestations in the Bu/MEL group appeared at a median of 29 days (range, 3-57 days) after ASCT. Mortality directly attributable to VOD was 2% in the Bu/MEL group and 0.2% in the MEL-200 group (P = .026). This high incidence of severe VOD probably had a multifactorial origin (busulfan followed by melphalan and previous use of BCNU). This observation should be kept in mind when designing future trials for the treatment of MM.
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Busulfano/efectos adversos , Enfermedad Veno-Oclusiva Hepática/inducido químicamente , Melfalán/administración & dosificación , Mieloma Múltiple/terapia , Agonistas Mieloablativos/administración & dosificación , Acondicionamiento Pretrasplante/efectos adversos , Adulto , Anciano , Busulfano/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Veno-Oclusiva Hepática/prevención & control , Humanos , Masculino , Melfalán/efectos adversos , Persona de Mediana Edad , Agonistas Mieloablativos/efectos adversos , Trasplante de Células Madre de Sangre Periférica/efectos adversos , España , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/efectos adversosRESUMEN
Recurrence of acute lymphoblastic leukemia (ALL) in the central nervous system (CNS) confers a poor prognosis, although to the authors' knowledge, only a few studies have analyzed this issue in adults. For the current study, the authors analyzed the frequency, predictive factors, and prognosis of CNS involvement and recurrence in adult patients with ALL who did not receive cranial irradiation for CNS prophylaxis. Four hundred sixty-seven adult patients (age > or = 15 years) with ALL were treated on 4 protocols: ALL-89 (standard-risk and high-risk ALL; n = 108 patients), ALL-93 (high-risk ALL; n = 222 patients), ALL-96 (standard-risk ALL; n = 84 patients), and ALL3-97 (Burkitt leukemia; n = 53 patients). CNS prophylaxis consisted of intrathecal methotrexate, cytarabine, and hydrocortisone together with high-dose systemic methotrexate and cytarabine. The mean age (+/- standard deviation) was 33 years (+/- 16 years), and 272 patients were males. ALL subtypes included an early pre-B phenotype (15%), a common phenotype (45%), a pre-B phenotype (5%), a mature B phenotype (11%), and a T phenotype (24%). CNS involvement at diagnosis was observed in 18 patients (3.9%). Of 159 recurrences, 22 occurred (5.8%) in the CNS (14 isolated and 8 combined). A lactate dehydrogenase level > 1000 U/L was the only factor associated with the risk of CNS recurrence. A complete remission was attained in 7 of 22 patients (32%). The median overall survival after recurrence was 0.7 years for patients with isolated CNS recurrence, 0.13 years for patients with combined recurrence, and 0.41 years for patients with bone marrow recurrence (P = .11). The only 2 survivors underwent stem cell transplantation. The frequency of CNS recurrence in adult patients with ALL who do not receive radiotherapy for CNS prophylaxis was similar to the frequency observed in protocols that included cranial irradiation. A lactate dehydrogenase value >1000 U/L was the only factor found to be associated with CNS recurrence. The prognosis for patients who develop CNS recurrence is poor, identical to that for patients who develop bone marrow recurrence.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/patología , Recurrencia Local de Neoplasia/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Adolescente , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias del Sistema Nervioso Central/prevención & control , Terapia Combinada , Irradiación Craneana , Citarabina/administración & dosificación , Femenino , Humanos , Hidrocortisona/administración & dosificación , Incidencia , Lactato Deshidrogenasas/análisis , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/prevención & control , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
La sepsis es una enfermedad severa que puede afectar a cualquier miembro de la población, causando graves consecuencias e incluso la muerte si no es tratada a tiempo. Está presente en un alto porcentaje en la población mundial y es la causa de muerte #23 en nuestro país, por ésta razón es de gran relevancia hacer un diagnóstico rápido y seguro de la enfermedad y así proporcionar tratamiento a la población afectada. El objetivo de este estudio fue determinar la sensibilidad, especificidad y exactitud de BRAHMS PCT®-Q, siendo éste una prueba para determinación de niveles de procalcitonina en sangre de manera semicuantitativa, para el diagnóstico precoz de sepsis y comparándolo con los resultados obtenidos por el hemocultivo y la impresión diagnóstica médica, siendo ésta última la prueba de referencia para el diagnóstico de sepsis bacterial. A partir de esto establecer la utilidad, así como los beneficios de una marcador de sepsis como la BRAHMS PCT®-Q en nuestro país. Para lograr esto se utilizó muestras de 102 pacientes que asistieron al Hospital de Clínicas Caracas, cuya sintomatología indicó que era recomendable realizar hemocultivo y determinación de procalcitonina. A estos pacientes se les hizo una toma de muestra para hemocultivo y en la misma punción se tomó una muestra de sangre sin anticoagulante. El hemocultivo fue procesado por el servicio de Bacteriología del Laboratorio del Hospital de Clínicas Caracas y el suero se utilizó para la determinación de procalcitonina. Una vez obtenidos ambos resultados se cotejaron y compararon. A partir de los datos obtenidos se pudo concluir que la sensibilidad de BRAHMS PCT®-Q es mayor al 80%, la especificidad es de 90% y presenta una exactitud de 90%. Por lo tanto es una prueba que puede ser utilizada para el diagnóstico precoz de sepsis...
Sepsis is a serious disease that may affect any member of the population and can have important consequences, including death, if not treated in time. It is present in a high percentage of the World population and is the 23rd cause of death in our country; it is therefore extremely relevant to diagnose the disease quickly and reliably and thus provide treatment to the affected population. The objective of this study consisted in determining the sensitivity, specificity and accurateness of the BRAHMS PCT®-Q, as a test to determine the levels of blood procalcitonin in a semi-quantitative manner for the early diagnosis of sepsis and comparing it with the results of the blood culture and medical impression, which is the benchmark test for the diagnosis of bacterial sepsis. And based on this, to establish the usefulness, as well as the benefits, of a sepsis marker, such as the BRAHMS PCT®-Q, in our country. To do so, samples of 102 patients, who visited the Hospital de Clínicas Caracas, were used; their symptomatology indicated that it was advisable to conduct a blood culture and determine procalcitonin. Of these patients a sample was taken for the blood culture, and with the same puncture a blood sample was taken without anticoagulant. The blood culture was processed using the services of the Bacteriological Department of the Hospital de Clínicas Caracas, and the serum was used to determine procalcitonin. Once both results were in, they were cross-tabulated and compared. Based on the data that was obtained, it could be concluded that the sensitivity of BRAHMS PCT®-Q is greater than 80%, its specificity is 90% which represents an accurateness of 90%. It is therefore a test that can be used for the early diagnosis of sepsis, but it is even more recommended to rule out the same...
Asunto(s)
Humanos , Masculino , Femenino , Bacteriemia/patología , Infecciones Bacterianas/patología , Infecciones Bacterianas/sangre , Sepsis/diagnóstico , Análisis Químico de la Sangre/métodos , Biología , HematologíaRESUMEN
En los estudios toxicológicos preclínicos del coralán, un proteoglucano obtenido en el INOR con perspectivas en el tratamiento antineoplásico, se observó la aparición de alteraciones inflamatorias locales en los animales de experimentación. Se preparó una formulación terapéutica con calidad inyectable y se comprobó que en tratamiento por la vía intramuscular en animales no se producían éstas alteraciones, lo que permite emplearlo en los estudios clínicos fase I
Asunto(s)
Ratas , Animales , Antineoplásicos/efectos adversos , Glicoproteínas/toxicidadRESUMEN
La experimentación farmacológica preclínica del coralán, un nuevo proteoglicano natural obtenido de un coral de los mares cubanos aportó evidencias sobre su efecto antitumoral indirecto en sistemas experimentales, por lo que se pasó al estudio y caracterización toxicológica del mismo. Se presentan resultados toxicológicos de interés, como es su carácter medianamente tóxico, el efecto local y general sobre el organismo, los principales blancos de su toxicidad, y se proponen las dosis iniciales para el ensayo clínico fase 1
Asunto(s)
Ratones , Ratas , Animales , Química Farmacéutica , Glicoproteínas/toxicidadRESUMEN
El (1-[2-cloroetil] 1-nitroso, 3 ciclohexil urea) (CCNU) es una droga antitumoral que forma parte actualmente de múltiples esquemas de poliquimioterapia en el tratamienmto de diferentes localizaciones y su obtención en el país aumentará la disponibilidad de este producto. El presente trabajo evalúa la actividad, en comparación con el producto comercial usado actualmente en la clínica oncológica y por los resultados obtenidos en los tumores experimentales utilizados, ambos productos manifiestan semejante actividad antitumoral
Asunto(s)
Ratones , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Leucemia L1210/tratamiento farmacológico , Leucemia P388/tratamiento farmacológicoRESUMEN
La búsqueda de nuevos inmunomoduladores con actividad antitumoral es tarea priorizada de muchos laboratorios en el mundo. En el Instituto Nacional de Oncología y Radiobiología (INOR) se obtuvo un polisacárido de un coral blanco del Caribe, que produjo rechazo al transplante de hasta 100 por ciento del tumor ascítico de Ehrlich en ratones. Este producto evidenci ó actividad de los linfocitos T a diferentes niveles en donantes sanos, lo que podría permitir en el futuro separar los mismos por el grado de incremento de respuesta a la PHA