RESUMEN
Nowadays, the infraorder Delphinida (oceanic dolphins and kin) represents the most diverse extant clade of Cetacea, with delphinids alone accounting for more than 40% of the total number of living cetacean species. As for other cetacean groups, the Early Miocene represents a key interval for the evolutionary history of Delphinida, as it was during this time span that the delphinidans became broadly distributed worldwide, first and foremost with the widespread genus Kentriodon and closely related forms. Here, we report on a new odontocete find from Burdigalian (20.4-19.0 Ma) deposits of the Friulian-Venetian Basin of northeastern Italy, consisting of the partial cranium of a small delphinidan with associated ear bones (right periotic, stapes, malleus and tympanic bulla). Osteoanatomical considerations and comparisons allow us to assign the studied specimen to the genus Kentriodon. This is the first confirmed record of Kentriodon from Europe as well as from the whole proto-Mediterranean region. Stratigraphic and phylogenetic considerations suggest that our new specimen may represent the geologically oldest member of Kentriodon. The evolutionary success of Kentriodon may correlate with the emergence of narrow-band high-frequency echolocation as a possible strategy to escape acoustic detection by large marine predators such as the squalodontids. In addition, the relatively high encephalization quotient of Kentriodon spp. may have provided these early dolphins with some kind of competitive advantage over the coeval non-delphinidan odontocetes.
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BACKGROUND: Calcified juxtafacet cysts in the cervical spine are extremely rate. Such symptomatic cysts commonly cause neck pain, radiculopathy, or even myelopathy. MR and CT studies typically document cord/ root compression. On occasion, some of these cysts will spontaneously regress, while many others may warrant surgical removal. CASE DESCRIPTION: A 70-year-old male presented with a 2-year history of a progressive tetraparesis. The preoperative MR/CT studies showed a C1-C2 left extradural mass occupying more than half of the spinal canal. On MR, it was homogeneously hypointense on both T1- and T2-weighted images, while the CT showed a calcified cyst. Intraoperative and histopathological findings documented a calcified cervical juxtafacet cyst (i.e. ganglion subtype) that was fully excised without sequelae. CONCLUSION: C1-C2 juxtafacet cervical cyst should be considered when a patient presents with myelopathy due to a calcified MR/CT documented paraspinal lesion contributing to significant cervical cord/root compression.
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The objective of this study was to investigate health-related quality of life (HRQOL), symptom burden, and comorbidity profile in long-term acute promyelocytic leukemia (APL) survivors treated with standard chemotherapy. Overall, 307 long-term APL survivors were invited to participate. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and compared with that of age and sex-matched controls from the general population. Symptom burden was assessed with the MD Anderson Symptom Inventory (MDASI) questionnaire and comorbidity profile was also investigated. Median follow-up time since diagnosis was 14.3 years (interquartile range: 11.1-16.9 years). APL survivors had a statistically and clinically meaningful worse score for the role physical scale of the SF-36 (-9.5; 95% CI, -15.7 to -3.2, P = 0.003) than their peers in the general population. Fatigue was reported as moderate to severe by 29% of patients and 84.4% reported at least one comorbidity. Prevalence of comorbidity in APL survivors was higher than that reported by the general population. Also, marked variations were found in the HRQOL profile by number of comorbidities. Even many years after treatment ends, APL survivors treated with standard chemotherapy do not fully recover as they report HRQOL limitations and a substantial burden of symptoms.
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Leucemia Promielocítica Aguda/epidemiología , Leucemia Promielocítica Aguda/terapia , Calidad de Vida , Índice de Severidad de la Enfermedad , Sobrevivientes/psicología , Adulto , Anciano , Estudios de Casos y Controles , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Italia/epidemiología , Leucemia Promielocítica Aguda/psicología , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Prevalencia , Pronóstico , Perfil de Impacto de Enfermedad , Encuestas y Cuestionarios , Tasa de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Choroid plexus tumors (CPTs) are rare neoplasms accounting for only 0.3-0.6% of all brain tumors in adults and 2-5% in children. The World Health Organization (WHO) classification describes three histological grades: grade I is choroid plexus papilloma (CPP), grade II is atypical papilloma, and grade III is the malignant form of carcinoma. In adults, CPTs rarely have a supratentorial localization. CASE DESCRIPTION: Here we report a very rare case of an intraparenchymal parietal CPP with a rapid histological transition from grade I to grade III WHO in a 67-year-old man, in <7 months. CONCLUSION: Because of the rarity of these oncotypes, descriptions of each new case are useful, mostly to consider this diagnostic entity in extraventricular brain tumors of adults, despite an unusual location.
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Orthopedic implants have become essential components of modern medicine. The risk of infection of total hip arthroplasty (THA) is 1.5%-2%. Are the C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) good markers for THA infection screenings? From February 2009 to December 2012 at our Department of Orthopedics and Traumatology, 1248 patients were treated with THA. No prosthesis was cemented. All patients received antibiotic prophylaxis. All patients were discharged approximately 7.4 days after surgery with this clinical and radiographic follow-up program at 15 days and 1, 3, 6, 12, 24, and 36 months after surgery. Blood samples to determine ESR, CRP, and PCT values were taken at 1 hour before surgery and 15 days and 1, 3, 6, 12, 24, and 36 months after surgery. During follow-ups there were 22 cases of THA infections; according the Widmer classification, infections are hematogenous ones in 16 cases, late chronic ones in 5 cases, and early postoperative ones in 1 case. In all cases the three markers were considered positive; in 6 cases there were no radiological signs of septic loosening. ESR, CRP, and PCT proved to have a greater diagnostic accuracy than X-rays in predicting late chronic and early postoperative infections. These markers are valuable support for the surgeon in monitoring the prosthetic implant lifespan.
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BACKGROUND: The sensitivity and the specificity of different methods to detect periprosthetic infection have been questioned. The current study aimed to investigate the kinetics of C-reactive protein (CRP) and procalcitonin (PCT) in patients undergoing uncomplicated elective total hip arthroplasty (THA), to provide a better interpretation of their levels in noninfectious inflammatory reaction. METHODS: A total of 51 patients were included. Serum CRP and PCT concentrations were obtained before surgery, on the 1st, 3rd, and 7th postoperative days and after discharge on the 14th and 30th days and at 2 years. RESULTS: Both markers were confirmed to increase after surgery. The serum CRP showed a marked increase on the 3rd postoperative day while the peak of serum PCT was earlier, even if much lower, on the first day. Then, they declined slowly approaching the baseline values by the second postoperative week. PCT mean values never exceed concentrations typically related to bacterial infections. CONCLUSIONS: CRP is very sensitive to inflammation. It could be the routine screening test in the follow-up of THA orthopaedic patients, but it should be complemented by PCT when there is the clinical suspicion of periprosthetic infection.
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Artroplastia de Reemplazo de Cadera , Proteína C-Reactiva/metabolismo , Calcitonina/sangre , Periodo Preoperatorio , Precursores de Proteínas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Péptido Relacionado con Gen de Calcitonina , Femenino , Humanos , Inflamación/sangre , Cinética , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Estudios Prospectivos , Factores de TiempoRESUMEN
In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; ≥75, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Clorambucilo/administración & dosificación , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Quimioterapia de Inducción , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Rituximab , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
In 45, ≤ 60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab(®)) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Vidarabina/análogos & derivados , Adulto , Alemtuzumab , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Análisis de Supervivencia , Resultado del Tratamiento , Vidarabina/administración & dosificación , Vidarabina/efectos adversosRESUMEN
PURPOSE: Cytarabine plays a pivotal role in the treatment of patients with acute myeloid leukemia (AML). Most centers use 7 to 10 days of cytarabine at a daily dose of 100 to 200 mg/m(2) for remission induction. Consensus has not been reached on the benefit of higher dosages of cytarabine. PATIENTS AND METHODS: The European Organisation for Research and Treatment of Cancer (EORTC) and Gruppo Italiano Malattie Ematologiche dell' Adulto (GIMEMA) Leukemia Groups conducted a randomized trial (AML-12; Combination Chemotherapy, Stem Cell Transplant and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia) in 1,942 newly diagnosed patients with AML, age 15 to 60 years, comparing remission induction treatment containing daunorubicin, etoposide, and either standard-dose (SD) cytarabine (100 mg/m(2) per day by continuous infusion for 10 days) or high-dose (HD) cytarabine (3,000 mg/m(2) every 12 hours by 3-hour infusion on days 1, 3, 5, and 7). Patients in complete remission (CR) received a single consolidation cycle containing daunorubicin and intermediate-dose cytarabine (500 mg/m(2) every 12 hours for 6 days). Subsequently, a stem-cell transplantation was planned. The primary end point was survival. RESULTS: At a median follow-up of 6 years, overall survival was 38.7% for patients randomly assigned to SD cytarabine and 42.5% for those randomly assigned to HD cytarabine (log-rank test P = .06; multivariable analysis P = .009). For patients younger than age 46 years, survival was 43.3% and 51.9%, respectively (P = .009; multivariable analysis P = .003), and for patients age 46 to 60 years, survival was 33.9% and 32.9%, respectively (P = .91). CR rates were 72.0% and 78.7%, respectively (P < .001) and were 75.6% and 82.4% for patients younger than age 46 years (P = .01) and 68.3% and 74.8% for patients age 46 years and older (P = .03). Patients of all ages with very-bad-risk cytogenetic abnormalities and/or FLT3-ITD (internal tandem duplication) mutation, or with secondary AML benefitted from HD cytarabine. CONCLUSION: HD cytarabine produces higher remission and survival rates than SD cytarabine, especially in patients younger than age 46 years.
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Antimetabolitos Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/administración & dosificación , Quimioterapia de Inducción/métodos , Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Quimioterapia de Consolidación , Daunorrubicina/administración & dosificación , Esquema de Medicación , Etopósido/administración & dosificación , Europa (Continente) , Femenino , Humanos , Infusiones Intravenosas , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Mutación , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
Givinostat, a histone-deacetylase inhibitor (HDACi), inhibits proliferation of cells bearing the JAK2 V617F mutation and has shown significant activity with good tolerability in patients with chronic myeloproliferative neoplasms (MPN). In this multicentre, open-label, phase II study, 44 patients with polycythaemia vera (PV), unresponsive to the maximum tolerated doses (MTD) of hydroxycarbamide (HC), were treated with Givinostat (50 or 100 mg/d) in combination with MTD of HC. The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12 weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100 mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100 mg groups, respectively. The combination of Givinostat and HC was well tolerated: eight patients (18%) discontinued, four in each treatment arm; grade 3 adverse events were reported in one patient (4·5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC-unresponsive PV patients.
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Carbamatos/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Hidroxiurea/uso terapéutico , Inhibidores de la Síntesis del Ácido Nucleico/uso terapéutico , Policitemia Vera/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Carbamatos/administración & dosificación , Carbamatos/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Femenino , Inhibidores de Histona Desacetilasas/administración & dosificación , Inhibidores de Histona Desacetilasas/efectos adversos , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Masculino , Persona de Mediana Edad , Inhibidores de la Síntesis del Ácido Nucleico/administración & dosificación , Inhibidores de la Síntesis del Ácido Nucleico/efectos adversos , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
In lower-risk myelodysplastic syndromes (MDS) with del(5q), lenalidomide induces erythroid responses associated with better survival. In a phase II, single-arm trial, 45 patients with anemia and lower-risk del(5q) MDS received lenalidomide 10 mg/day to evaluate quality of life (QoL) changes, measured by QOL-E, safety, responses and survival. Lenalidomide was well tolerated, with 80% completing ≥ 24 weeks of treatment. Earlier study discontinuation was related to disease progression (n = 5), death (n = 1) and withdrawal of consent (n = 3). Within 24 weeks, 82% obtained erythroid responses, durable in 69% at 52 weeks. Cytogenetic responses occurred in 29 patients (64%), with 10 patients achieving a complete cytogenetic response. QoL-E scores correlated with hemoglobin levels and improved in erythroid responders. Erythroid responders had an 86% reduced risk of disease progression and an 80% reduction in mortality risk compared with non-responders. These findings corroborate earlier studies and give further support to the use of lenalidomide in lower-risk MDS and del(5q).
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Inhibidores de la Angiogénesis/uso terapéutico , Deleción Cromosómica , Cromosomas Humanos Par 5 , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Talidomida/análogos & derivados , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Calidad de Vida , Talidomida/efectos adversos , Talidomida/uso terapéutico , Resultado del TratamientoRESUMEN
In vitro studies suggest that haploinsufficiency is involved in the pathogenesis of myelodysplastic syndromes (MDS). In patients with del5q cytogenetic abnormality, RPS-14 and microRNAs (miRNAs) play a major role. In a multicenter phase II single-arm trial with lenalidomide in anemic primary del5q MDS patients with low- or int-1 risk IPSS, biological changes from baseline were investigated. Gene expression profiling of selected genes was performed (TaqMan® Low Density Array Fluidic card, Applied Biosystems PRISM® 7900HT) and normalized against the expression of the 18S housekeeping gene from a pool of healthy subjects. Thirty-two patients were evaluated at baseline and after 3 and 6 months of treatment. RPS-14, miR-145, and miR-146 were downregulated at baseline and significantly increased during treatment. Nuclear factor kappa B, IL-6, interferon regulatory factor-1, IFNγ-R2, IL-2, and many genes in the apoptotic pathways (TNF, IL-1B, and IL-10) were upregulated at baseline and significantly downregulated during lenalidomide treatment, while forkhead box P3, FAS, IFNγ, IL-12A, and IL-12B were downregulated at baseline and progressively upregulated during treatment. The crucial role of aberrant immunological pathways and haploinsufficiency in the pathogenesis of del5q MDS is confirmed in the present patient setting. Our results indicate that lenalidomide may act through defined immunological pathways in this condition.
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Anemia Macrocítica/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Síndromes Mielodisplásicos/genética , Talidomida/análogos & derivados , Anciano , Anemia Macrocítica/tratamiento farmacológico , Anemia Macrocítica/inmunología , Apoptosis/genética , Apoptosis/inmunología , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Deleción Cromosómica , Cromosomas Humanos Par 5/genética , Cromosomas Humanos Par 5/inmunología , Femenino , Factores de Transcripción Forkhead/biosíntesis , Factores de Transcripción Forkhead/genética , Dosificación de Gen , Estudios de Asociación Genética , Humanos , Inmunidad Innata/genética , Lenalidomida , Masculino , MicroARNs/biosíntesis , MicroARNs/genética , Modelos Genéticos , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/inmunología , Proteínas Ribosómicas/deficiencia , Proteínas Ribosómicas/genética , Transducción de Señal/genética , Transducción de Señal/inmunología , Talidomida/farmacología , Talidomida/uso terapéuticoRESUMEN
Dasatinib is a potent BCR-ABL inhibitor effective in chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia (ALL) resistant/intolerant to imatinib. In the GIMEMA LAL1205 protocol, patients with newly diagnosed Ph(+) ALL older than 18 years (with no upper age limit) received dasatinib induction therapy for 84 days combined with steroids for the first 32 days and intrathecal chemotherapy. Postremission therapy was free. Fifty-three patients were evaluable (median age, 53.6 years). All patients achieved a complete hematologic remission (CHR), 49 (92.5%) at day 22. At this time point, 10 patients achieved a BCR-ABL reduction to < 10(-3). At 20 months, the overall survival was 69.2% and disease-free survival was 51.1%. A significant difference in DFS was observed between patients who showed at day 22 a decrease in BCR-ABL levels to < 10(-3) compared with patients who never reached these levels during induction. In multivariate analysis, BCR-ABL levels of < 10(-3) at day 85 correlated with disease-free survival. No deaths or relapses occurred during induction. Twenty-three patients relapsed after completing induction. A T315I mutation was detected in 12 of 17 relapsed cases. Treatment was well tolerated; only 4 patients discontinued therapy during the last phase of the induction when already in CHR. In adult Ph(+) ALL, induction treatment with dasatinib plus steroids is associated with a CHR in virtually all patients, irrespective of age, good compliance, no deaths, and a very rapid debulking of the neoplastic clone.
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Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pirimidinas/uso terapéutico , Tiazoles/uso terapéutico , Adulto , Anciano , Antígenos CD/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dasatinib , Esquema de Medicación , Femenino , Citometría de Flujo , Proteínas de Fusión bcr-abl/genética , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunofenotipificación , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/administración & dosificación , Recurrencia , Inducción de Remisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esteroides/administración & dosificación , Tiazoles/administración & dosificación , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
We retrospectively analyzed the data of 337 patients with cytogenetically normal (CN) acute myeloid leukemia (AML), aged ≤ 65 years (training set). A prognostic index score (PIS) was calculated by totaling the score derived from the regression coefficients of each clinical variable, significantly associated with prognosis by multivariate analysis. The variables that were independent prognostic factors for event-free survival (EFS) and overall survival (OS) in the training set were: age ≥ 50 years, secondary AML and white blood cell count (WBC) ≥ 20 × 10(9)/L. The patients of the training set were stratified into three groups: low-, intermediate- and high-risk. The median EFS was 25, 12 and 7 months in the low-, intermediate- and high-risk groups (p < 0.0001), respectively. The median OS was not reached in the low-risk group and was 19 and 10 months in the intermediate- and high-risk groups (p < 0.0001). This PIS was validated in a series of 193 patients with CN-AML. The median EFS was 66, 16, and 3 months (p < 0.0001) and the median OS was 66, 16, and 5 months in the three risk groups, respectively (p < 0.0001). This PIS may be useful for clinical decision-making in CN-AML and may be prospectively integrated with the newest biological markers which at present are not routinely assessed and need prognostic validation.
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Leucemia Mieloide Aguda/diagnóstico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Cariotipificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
All-trans-retinoic acid (ATRA) has greatly modified the prognosis of acute promyelocytic leukemia; however, the role of maintenance in patients in molecular complete remission after consolidation treatment is still debated. From July 1993 to May 2000, 807 genetically proven newly diagnosed acute promyelocytic leukemia patients received ATRA plus idarubicin as induction, followed by 3 intensive consolidation courses. Thereafter, patients reverse-transcribed polymerase chain reaction-negative for the PML-RARA fusion gene were randomized into 4 arms: oral 6-mercaptopurine and intramuscular methotrexate (arm 1); ATRA alone (arm 2); 3 months of arm1 alternating to 15 days of arm 2 (arm 3); and no further therapy (arm 4). Starting from February 1997, randomization was limited to ATRA-containing arms only (arms 2 and 3). Complete remission was achieved in 761 of 807 (94.3%) patients, and 681 completed the consolidation program. Of these, 664 (97.5%) were evaluated for the PML-RARA fusion gene, and 586 of 646 (90.7%) who tested reverse-transcribed polymerase chain reaction-negative were randomized to maintenance. The event-free survival estimate at 12 years was 68.9% (95% confidence interval, 66.4%-71.4%), and no differences in disease-free survival at 12 years were observed among the maintenance arms.
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Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Promielocítica Aguda/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Preescolar , Protocolos Clínicos , Supervivencia sin Enfermedad , Femenino , Humanos , Idarrubicina/administración & dosificación , Lactante , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/genética , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Inducción de Remisión , Tretinoina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to evaluate changes in quality of life scores and their association with therapy and survival in unselected elderly patients with acute myeloid leukemia. DESIGN AND METHODS: From February 2003 to February 2007, 113 patients aged more than 60 years with de novo acute myeloid leukemia were enrolled in a prospective observational study. Two different quality of life instruments were employed: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) and a health-related quality of life questionnaire for patients with hematologic diseases (QOL-E). RESULTS: Forty-eight patients (42.4%) received intensive chemotherapy and 65 (57.6%) were given palliative treatments. Age greater than 70 years (P=0.007) and concomitant diseases (P=0.019) had a significant impact on treatment allocation. At diagnosis, general quality of life was affected [median QOL-E standardized score 54, interquartile range 46-70; median EORTC global score 50, interquartile range 41-66]. Most patients were given a good ECOG Performance Status (< 2), which did not correlate with the patients' perception of quality of life. At multivariate analysis, palliative approaches (P=0.016), age more than 70 years (P=0.013) and concomitant diseases (P=0.035) each had an independent negative impact on survival. In a multivariate model corrected for age, concomitant diseases and treatment option, survival was independently predicted by QOL-E functional (P=0.002) and EORTC QLQ-C30 physical function (P=0.030) scores. CONCLUSIONS: Quality of life could have an important role in elderly acute myeloid leukemia patients at diagnosis as a prognostic factor for survival and a potential factor for treatment decisions.
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Leucemia Mieloide/psicología , Leucemia Mieloide/terapia , Calidad de Vida , Encuestas y Cuestionarios , Enfermedad Aguda , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Cuidados Paliativos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios ProspectivosRESUMEN
BACKGROUND: Haploinsufficiency of the ribosomal protein S14 RPS14 gene, located in the common deleted region of chromosome 5q, is a potential causal factor of 5q- syndrome. Lenalidomide elicits high response rates and morphological improvements in myelodysplastic syndrome (MDS) patients with chromosome 5q deletion [del(5q)]. METHODS: To further evaluate the role of RPS14, its transcription was tested in bone marrow cells from 17 patients with International Prognostic Scoring System defined Low- or Intermediate-1-risk MDS with del(5q) as a single or additional cytogenetic abnormality receiving treatment with lenalidomide. RESULTS: After 12 wk of lenalidomide treatment, erythroid responses were observed in all cases with an increase in hemoglobin levels of 2.7 +/- 2.5 g/dL (up to a mean 11.8 +/- 1.9 g/dL; P = 0.001). Before treatment, RPS14 expression levels were under-expressed in 15 patients with respect to normal controls. After 12 wk of lenalidomide treatment, all patients had an erythroid response. There was a significant increase in median RPS14 expression from baseline 0.01 (IQR 0.05-0.31) to 12 wk 204.71-fold (2.86-446.32; P < 0.0001). CONCLUSIONS: These observations in the patient setting support the importance of RPS14 in the pathogenesis of MDS with del(5q).
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Deleción Cromosómica , Cromosomas Humanos Par 5/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Proteínas Ribosómicas/genética , Talidomida/análogos & derivados , Anciano , Análisis Citogenético , Femenino , Humanos , Lenalidomida , Masculino , Factores de Riesgo , Talidomida/uso terapéutico , Transcripción Genética/efectos de los fármacos , Transcripción Genética/genéticaRESUMEN
To evaluate efficacy, safety, changes in biological features, and quality of life (QoL) in low-risk anemic patients with MDS treated with darbepoetin alfa (DPO), 41 patients received DPO 150 microg weekly for 24 weeks. The dose was increased to 300 microg weekly in non-responsive patients. During treatment, 10/17 (59%) transfusion-dependent (TD) and 13/23 (56%) transfusion-free (TF) patients responded. In TF patients, Hb increased from 9.2 +/- 0.9 g/dL to 10.3 +/- 1.4 g/dL by 24 weeks (p = 0.004). The mean response duration was 22 weeks (95% CI: 19.7-24.0) in TF patients compared with 15.1 weeks (95% CI: 13.3-17.5) in TD patients. Response to treatment was associated with increases in QoL. Decreases in the percentage of apoptotic progenitor cells (p = 0.007) and CD34+ cells (p = 0.005) were observed. These results confirm previous studies demonstrating the safety and efficacy of DPO in anemic patients with MDS. Biological changes and improvement in QoL were associated with response. Adequate dosing is to be determined.
Asunto(s)
Anemia/tratamiento farmacológico , Eritropoyetina/análogos & derivados , Síndromes Mielodisplásicos/complicaciones , Anciano , Anciano de 80 o más Años , Anemia/complicaciones , Anemia/terapia , Transfusión Sanguínea , Terapia Combinada/estadística & datos numéricos , Darbepoetina alfa , Relación Dosis-Respuesta a Droga , Eritropoyetina/uso terapéutico , Femenino , Hematínicos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Calidad de Vida , Análisis de Regresión , Resultado del TratamientoRESUMEN
BACKGROUND: It is well known that iron overload may cause multiple organ failure. In chronically transfused patients, optimal iron chelation therapy is associated with reduced morbidity and mortality. Furthermore, chelation therapy has been associated with erythroid responses. STUDY DESIGN AND METHODS: Among chronically transfused adults affected by myeloproliferative neoplasms and treated with iron chelators, two case reports are described. CASE REPORT: A male adult patient with myelodysplastic syndrome (MDS) and a female adult with aplastic anemia (AA), both transfusion-dependent, were treated with deferasirox, an oral iron chelator. RESULTS: A significant reduction in transfusion requirement was observed and was dependent on chelation therapy. The patient affected by AA also experienced a significant increase in hemoglobin levels. Minimal doses of deferasirox maintained the erythroid responses. Many mechanisms of action of the drug on erythropoiesis have been postulated. The early erythroid response seems to be independent of the removal of iron from deposits, per se, since the reduction of ferritin levels (a surrogate marker of iron deposits) below threshold levels occurs as a later event. CONCLUSION: Although there are few reports on erythroid responses in patients undergoing iron chelation therapy, they may give new insights in the pathogenesis of MDS and other myeloproliferative neoplasms. AA may benefit in terms of erythroid response. The findings in these cases underline the clinical importance of treating patients with iron overload. A survival benefit of chelation in patients with myeloproliferative neoplasms is still to be confirmed.
Asunto(s)
Benzoatos/uso terapéutico , Transfusión Sanguínea , Hematopoyesis/efectos de los fármacos , Quelantes del Hierro/uso terapéutico , Triazoles/uso terapéutico , Anemia Aplásica/sangre , Anemia Aplásica/terapia , Deferasirox , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/terapiaRESUMEN
A recurrent specific JAK2 V617F mutation has been reported in bcr/abl-negative chronic myeloproliferative diseases (cMPD), including polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). The mutation is detectable in a variable proportion of neoplastic clones, depending on the molecular methods employed. In this study, we attempted to establish the JAK2 V617F mutation frequency in two partially overlapping cMPD patient series by two different PCR-based techniques. Using an allele-specific polymerase chain reaction assay (AS-PCR), the JAK2 V617F mutation was detected in 124/158 (78.5%) cMPD patients; in particular, 90.2, 72.1, 63.2 and 50% of PV, ET, IMF and unclassified (U)-MPD cases, respectively, showed the mutation. Employing a semiquantitative 5' fluorogenic TaqMan assay, the JAK2 V617F mutation was identified in a much larger percentage of cMPDs patients (118/127: 92.9%). Rates of mutation in PV, ET, IMF and U-MPD cases were 95.9, 85.7, 91.7 and 92.9%, respectively. Furthermore, a statistically higher percentage of JAK2 mutated alleles was detected by TaqMan assay in PV (68+/-3.5, mean value+/-SEM) and IMF (64+/-9.3) cases as compared with ET (35+/-5.4). Finally, a significant correlation between JAK2 V617F mutational status and hematocrit (Ht), white blood cell and platelet counts in PV patients, and Ht values in ET cases, was observed by AS-PCR. Overall, these data indicate that TaqMan technology significantly improved sensitivity in detecting the JAK2 mutation in cMPD patients and may be worth of further evaluations as a clinically useful tool for detection of small amounts of mutated clones.