RESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option in advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS). This study presents an updated analysis of the initial experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT) describing the outcomes after allo-HSCT for MF and SS, with special emphasis on the impact of the use of unrelated donors (URD). METHODS AND PATIENTS: Eligible for this study were patients with advanced-stage MF or SS who underwent a first allo-HSCT from matched HLA-identical related or URD between January/1997 and December/2011. Sixty patients have been previously reported. RESULTS: 113 patients were included [77 MF (68%)]; 61 (54%) were in complete or partial remission, 86 (76%) received reduced-intensity protocols and 44 (39%) an URD allo-HSCT. With a median follow up for surviving patients of 73 months, allo-HSCT resulted in an estimated overall survival (OS) of 38% at 5 years, and a progression-free survival (PFS) of 26% at 5 years. Multivariate analysis demonstrated that advanced-phase disease (complete remission/partial remission >3, primary refractory or relapse/progression in patients that had received 3 or more lines of systemic treatment prior to transplant or the number of treatment lines was not known), a short interval between diagnosis and transplant (<18 months) were independent adverse prognostic factors for PFS; advanced-phase disease and the use of URDs were independent adverse prognostic factors for OS. CONCLUSIONS: This extended series supports that allo-HSCT is able to effectively rescue over one third of the population of patients with advanced-stage MF/SS. High relapse rate is still the major cause of failure and needs to be improved with better strategies before and after transplant. The negative impact of URD is a matter of concern and needs to be further elucidated in future studies.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Medula Óssea , Humanos , Micose Fungoide/terapia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Síndrome de Sézary/terapia , Transplante HomólogoRESUMO
BACKGROUND: Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish whether the incidence of irAEs after the use of anti-PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti-PD-1 treatment efficacy. PATIENTS AND METHODS: We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer. irAEs (immune-related adverse events) were identified clinically and graded as per the Common Terminology Criteria for Adverse Events version 4.0. Efficacy was evaluated with objective response rate (ORR, immune-Response Evaluation Criteria in Solid Tumours [RECIST] criteria) progression-free survival (PFS) and overall survival (OS). Tests were performed to determine the association between irAEs and ORR, PFS or OS. RESULTS: We identified 106 patients. Primary diagnoses were lung cancer (n = 77), melanoma (n = 8), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma (n = 1 each). IrAEs were observed in 40 patients (37.7%). The most frequent irAEs were hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 44 patients (41.5%), and median PFS was 5.5 months (0.5-31 months). Thirty-three of the 40 patients with irAEs had objective response (82.5%) in contrast with 11 of the 66 cases without irAEs (16.6%) (OR 23.5, P < 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without irAEs (HR 2.2, P = 0.016). OS in patients with irAEs was 32 months and 22 in those without irAEs, without statistically significant differences. CONCLUSION: In advanced cancer treated with single-agent anti-PD-1 antibodies, patients with irAEs showed a markedly improved efficacy over patients without irAEs (ORR of 82.5% and PFS of 10 months vs ORR of 16.6% and PFS of 3 months). Future studies of anti-PD-1 immune-therapy should address this association to explore the underlying biological mechanisms of efficacy.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Prognóstico , Taxa de SobrevidaRESUMO
Guidelines recommend autologous stem cell transplantation (ASCT) consolidation in first complete or partial response after regimens including rituximab (R) and high-dose AraC (HDAC), but its use beyond that response is questioned. We present a retrospective analysis of 268 patients with MCL who received ASCT. With a median follow-up for survival patients of 54 months, progression-free survival and overall survival for the whole series were 38 and 74 months, respectively, and for patients transplanted in first CR 49 and 97 months, respectively. Patients without CR before transplant were analyzed separately, those who achieved CR after transplantation had better PFS (48 vs 0.03 months, p < 0.001) and OS (92 vs 16 months, p < 0.001) than the remaining. In univariate analysis, first CR at transplant (p = 0.01) and prior rituximab (p = 0.02) were the variables associated with PFS. For OS, the same variables resulted significant (p = 0.03 and p < 0.001, respectively). In multivariate analysis, only the status at transplant (first CR) remained significant. This retrospective study concludes that ASCT consolidation in first CR induces high survival rates. In other stages of disease, the need of ASCT as consolidation may be questioned.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Célula do Manto/terapia , Adulto , Idoso , Citarabina/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Rituximab/administração & dosagem , Condicionamento Pré-Transplante , Transplante Autólogo , Adulto JovemRESUMO
Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Compostos de Mostarda Nitrogenada/uso terapêutico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Cloridrato de Bendamustina , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Linfoma de Célula do Manto/epidemiologia , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Espanha/epidemiologia , Falha de TratamentoRESUMO
BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.
Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/cirurgia , Recidiva Local de Neoplasia/mortalidade , Transplante de Células-Tronco , Adolescente , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Sobrevida , Transplante Autólogo , Falha de Tratamento , Adulto JovemRESUMO
The coexistence of non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD) in the same patient, although previously reported, is very unusual. This situation is extremely rare when the first diagnosis is a cutaneous B NHL, and exceptional if there is no personal background of cytostatic treatment. We report a 44-year-old man who developed cutaneous nodules over a period of two years. A marginal zone cutaneous B-cell lymphoma was diagnosed. On staging investigation a mass in the lingual tonsil was found and excision biopsy showed a classical Hodgkin lymphoma.
Assuntos
Doença de Hodgkin/patologia , Linfoma de Zona Marginal Tipo Células B/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Cutâneas/patologia , Neoplasias Tonsilares/patologia , Adulto , Humanos , MasculinoRESUMO
Central nervous system (CNS) involvement by Hodgkin Lymphoma (HL) is rarely reported. Retrospective and prospective cohort studies suggest an incidence of 0.2-0.5%, mostly in relapsed disease. In spite of a 3 to 18-fold increased risk of HL in patients with human immunodeficiency virus (HIV), only two cases have been reported so far. In this paper, we now report a third case of HIV patient with HL who progressed with isolated CNS infiltration after a standard chemotherapy induced clinical remission. In 1991, when the first case of intracerebral involvement in HIV+ HL was reported an increase of this type of cases would have been expected, but only one more case has been reported since then.
Assuntos
Neoplasias Encefálicas/patologia , Infecções por HIV/patologia , HIV , Doença de Hodgkin/patologia , Adulto , Neoplasias Encefálicas/complicações , Infecções por HIV/complicações , Doença de Hodgkin/complicações , Humanos , MasculinoRESUMO
BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas associated with poor prognosis with standard chemotherapy. Consolidation with autologous stem-cell transplantation (ASCT) may improve survival. We present 74 patients transplanted in first complete response (CR) from the Spanish Lymphoma and Autologous Transplantation Group cooperative group. PATIENTS AND METHODS: Median age was 46 years. Eighty-eight percent presented advanced (III-IV) Ann Arbor stage; 53% had B symptoms; 52% had high lactate dehydrogenase; 65% had two or three risk factors of the adjusted-International Prognostic Index; 58% presented a high Tumor score and in 14% more than two adverse factors of the Prognostic Index for peripheral T-cell lymphoma (PIT) were observed. RESULTS: With a median follow-up of 67 months from diagnosis, the 5-year overall survival (OS) was 68% and progression-free survival (PFS) reached 63%. The multivariate analysis showed that the only factor associated with a shorter OS and PFS was the presence of more than two risk factors from the PIT risk system. CONCLUSIONS: In a retrospective study with a prolonged follow-up, consolidation with ASCT in CR patients who had presented unfavorable prognostic factors at diagnosis substantially increased the OS and PFS when compared with conventional chemotherapy. The PIT risk system identified 14% of patients without benefit from ASCT consolidation. Thus, other innovative therapies are still necessary in certain cases.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Linfoma de Células T Periférico/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante AutólogoRESUMO
OBJECTIVE: to perform a retrospective review of the clinical characteristics and prevalence of H. pylori infection in patients with gastric MALT lymphoma diagnosed in our hospital during the last 15 years. METHODS: patients with gastric MALT lymphoma diagnosed in our hospital during the last 15 years were retrospectively included. Demographic, clinic, analytic, endoscopic, and histological variables were reviewed. The extension study, the staging classification, and the presence of H. pylori infection were assessed. RESULTS: thirty-seven patients with gastric MALT lymphoma were identified. Mean age was 61 years, with 62% of males. The most common presentation symptom was dyspepsia (76%), followed by digestive bleeding (11%) and constitutional syndrome (8%). At endoscopy, erosive lesions were identified in 41%, and proliferative or exophytic lesions in 43%. Most lymphomas were classified as low-grade (68%). The stage distribution was EI for 56%, EII for 13%, EIII for 3%, and EIV for 28%. The prevalence of H. pylori infection (histology in all cases, rapid urease test in 19%, and 13C-urea breath test in 24%) was 46%. When only low-grade lymphomas in stage EI were considered, H. pylori prevalence increased to 55%. When H. pylori infection was evaluated by 13C-urea breath testing (in addition to histology), the prevalence of H. pylori infection increased to 78%. CONCLUSIONS: it is probable that the reduced H. pylori prevalence found in some studies, as in ours, could be explained by false-negative results obtained when only one diagnostic method was used. Therefore, at least two (invasive) diagnostic methods should be performed. Furthermore, the performance of a non-invasive diagnostic method (such as a 13C-urea breath test) before the exclusion of H. pylori infection should be considered.
Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Idoso , Feminino , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos RetrospectivosRESUMO
Previous studies of the structure of core nanocrystals of ferritin (Ft) in the brains of patients with Alzheimer's disease (AD) have shown differences in the mineral compound in comparison with physiological Ft. Both Ft cores have a polyphasic composition but whereas the major phase in physiological Ft is hexagonal ferric iron oxide (ferrihydrite), the major phases in brain AD Ft are two cubic mixed ferric-ferrous iron oxides (magnetite and wüstite). One of these (wüstite) is similar to what is detected in hemosiderin (Hm) cores in primary hemochromatosis (Quintana, C., Cowley, J.M, Marhic, C., 2004. Electron nanodiffraction and high resolution electron microscopy studies of the structure and composition of physiological and pathological ferritin. J. Struct. Biol. 147, 166-178). We have studied, herein, the distribution of iron, Ft, and Hm in sections of AD hippocampus using analytical microscopy. Iron present in Ft cores was directly mapped in a nanoSIMS microscope and the iron distribution has been correlated with the constituent elements N, P, and S. Ft and Hm cores were visualized at an ultrastructural level in an analytical transmission electron microscope. In senile plaques, Ft was observed in the coronal region associated with a non-beta-amyloid component and in the periphery of plaques, together with Hm, in sulfur-rich dense bodies of dystrophic neurites. Hm was also found in lysosomes and siderosomes of glial cells. Ft was observed in the cytoplasm and nucleus of oligodendrocytes. Ft was particularly abundant in myelinated axons in association with oligodendrocyte processes. These findings provide new arguments to support the hypothesis of a dysfunction of Ft (with eventual degradation to Hm) in AD resulting in an increase of toxic brain ferrous ions that may contribute to the production of free radicals that induce both cellular oxidative stress and aged-related myelin breakdown associated with cognitive decline and AD (Bartzokis, G., 2004. Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. Neurobiol. Aging 25, 5-18).
Assuntos
Doença de Alzheimer/patologia , Ferritinas/análise , Hemossiderina/análise , Hipocampo/química , Ferro/análise , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Axônios/química , Axônios/ultraestrutura , Feminino , Hipocampo/ultraestrutura , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Bainha de Mielina/química , Bainha de Mielina/ultraestrutura , Espectrometria de Massa de Íon Secundário/métodosAssuntos
Doenças do Sistema Imunitário/etiologia , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/terapia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Antígenos CD34 , Humanos , Doenças do Sistema Imunitário/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante AutólogoRESUMO
PURPOSE: To analyse outcome and prognostic factors for overall survival (OS) and time to treatment failure (TTF) in 357 patients with Hodgkin's lymphoma (HL) undergoing an autologous stem cell transplantation (ASCT) after a first relapse and reported to the The Grupo Espanol de Linfomas/Trasplante Autologo de Medula Osea (GEL/TAMO) Cooperative Group. METHODS: Two hundred and twenty males and 137 females with a median age of 29 years were autografted in second remission (n=181), first sensitive relapse (n=148) and first resistant relapse (n=28). RESULTS: Five-year actuarial TTF and OS were of 49% +/- 3% and 57% +/- 3%. Advanced stage at diagnosis, complementary radiotherapy before ASCT, a short first complete response (CR) and detectable disease at ASCT adversely influenced TTF. Year of transplant < or =1995, bulky disease at diagnosis, a short first CR, detectable disease at ASCT and > or =1 extranodal areas involved at ASCT were adverse factors for OS. CONCLUSIONS: ASCT constitutes a therapeutic option for HL patients after a first relapse. Promising results are observed in patients with low tumour burden at diagnosis, autografted after a long CR and without detectable disease at ASCT. Innovative approaches should be pursued for patients with risk factors at relapse.
Assuntos
Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Doença de Hodgkin/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Transplante de Células-Tronco/estatística & dados numéricos , Tempo , Transplante Autólogo , Resultado do TratamentoRESUMO
PURPOSE: To determine whether interferon (IFN) -alpha2, when given with or following chemotherapy, influences response rate, remission duration, and survival in newly diagnosed patients with follicular lymphoma. PATIENTS AND METHODS: Ten phase III studies evaluating the role of IFN-alpha2 in 1,922 newly diagnosed patients with follicular lymphoma were analyzed. Updated individual patient data were used to perform meta-analyses for response, survival, and remission duration. RESULTS: The addition of IFN-alpha2 to initial chemotherapy did not significantly influence response rate. An overall meta-analysis for survival showed a significant difference in favor of IFN-alpha2, but also showed significant heterogeneity between studies. Further analyses were carried out in order to explain this heterogeneity, and to define the circumstances in which IFN-alpha2 prolonged survival. The survival advantage was seen when IFN-alpha2 was given: (1) in conjunction with relatively intensive initial chemotherapy (2P = .00005), (2) at a dose >/= 5 million units (2P = .000002), (3) at a cumulative dose >/= 36 million units per month (2P = .000008), and (4) with chemotherapy rather than as maintenance therapy (P = .004). With regard to remission duration, there was also a significant difference in favor of IFN-alpha2, irrespective of the intensity of chemotherapy used, IFN dose, or whether IFN was given as a maintenance strategy or with chemotherapy. CONCLUSION: When given in the context of relatively intensive initial chemotherapy, and at a dose >/= 5 million units (>/= 36 x 10(6) units per month), IFN-alpha2 prolongs survival and remission duration in patients with follicular lymphoma.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interferon-alfa/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase II como Assunto , Esquema de Medicação , Feminino , Humanos , Interferon alfa-2 , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Here we evaluate the results of high-dose chemotherapy and autologous stem-cell transplantation (HDC/ASCT) in 114 patients included in the GEL/TAMO registry between January 1990 and December 1999 with diffuse large B-cell lymphoma who failed to achieve complete remission (CR) with front-line conventional chemotherapy. PATIENTS AND METHODS: Sixty-eight per cent had a partial response (PR) and 32% failed to respond to front-line therapy. At transplant, 35% were chemoresistant and 29% had two to three adjusted International Prognostic Index (a-IPI) risk factors. RESULTS: After HDC/ASCT, 57 (54%) of 105 patients evaluable for response achieved a CR, 16 (15%) a PR and 32 (30%) failed. Nine patients were not assessed for response because of early death due to toxicity. With a median follow-up of 29 months for alive patients, the survival at 5 years is 43%, with a disease-free survival for complete responders of 63%. The lethal toxicity was 8%. Multivariate analysis revealed a-IPI and chemoresistance to be predicting factors. CONCLUSIONS: Our results show that one-third of patients who do not obtain a CR to front-line chemotherapy may be cured of their disease with HDC/ASCT. However, most chemoresistant patients pretransplant failed this therapy. For this population, as well as for those who presented with adverse factors of the a-IPI, pretransplant novel therapeutic modalities need to be tested.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Linfoma de Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Autólogo , Resultado do TratamentoRESUMO
Caspofungin, an echinocandin antifungal agent, is active against invasive Aspergillus and Candida infections. In a phase I study in healthy volunteers, mild transient increases in serum aminotransferases were observed with the concomitant administration of caspofungin and cyclosporin A (CsA). As a result, it is recommended that the concomitant use of the two drugs be limited to those settings with appropriate risk-benefit balance. We retrospectively assessed safety data in 14 patients with refractory invasive mycoses who were treated concomitantly with CsA and caspofungin before the drug was licensed in Spain. In all, 13 patients were adults (median age, 31.5 years; range, 14-67 years). The average duration of concomitant therapy was 15 days (range, 2-43 days). No clinically significant elevations of serum aminotransferases were observed, and no patient had concomitant therapy discontinued or interrupted due to a drug-related adverse event. In this study of a limited number of patients, the coadministration of caspofungin and CsA was generally well tolerated.
Assuntos
Ciclosporina/uso terapêutico , Micoses/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Adolescente , Adulto , Idoso , Antifúngicos/uso terapêutico , Antifúngicos/toxicidade , Caspofungina , Ensaios Enzimáticos Clínicos , Ciclosporina/toxicidade , Avaliação de Medicamentos , Quimioterapia Combinada , Equinocandinas , Feminino , Humanos , Lipopeptídeos , Masculino , Pessoa de Meia-Idade , Micoses/complicações , Peptídeos Cíclicos/toxicidade , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: T-cell immunophenotype constitutes an unfavorable prognostic factor in aggressive non-Hodgkin's lymphomas. High-dose chemotherapy with autologous stem-cell rescue (HDC/ASCT) is the best salvage therapy for patients with aggressive B-cell lymphomas. However, results with this therapy in peripheral T-cell lymphoma (PTCL) are not well defined. PATIENTS AND METHODS: From January 1990 to December 1999, 115 patients with PTCL underwent HDC/ASCT inside the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) registry. At diagnosis the median age was 41 years and 60% of patients presented with two or three risk factors from the adjusted International Prognostic Index (a-IPI). Thirty-two per cent of patients were transplanted in first complete response (CR), 62% in chemosensitive disease and 5% in refractory disease. RESULTS: Eighty-six per cent of the patients attained a CR and 5% a partial response (PR). With a median follow-up of 37 months (range 1-133), overall survival (OS), time-to-treatment failure (TTF) and disease-free survival (DFS) at 5 years was 56%, 51% and 60%, respectively; for the 37 patients transplanted in first CR, OS and DFS at 5 years were 80% and 79%, respectively. Lactase dehydrogenase (LDH), a-IPI and disease status pre-transplant were associated with outcome. CONCLUSIONS: More than half of patients with chemosensitive disease who were transplanted are expected to be alive at 5 years. We confirm the utility of the pre-transplant IPI system in predicting outcome. Salvage treatment results with HDC/ASCT in PTCL are similar to those found in corresponding aggressive B-cell lymphomas.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carmustina/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Transplante Autólogo , Resultado do Tratamento , Irradiação Corporal TotalRESUMO
BACKGROUND: Patients with primary refractory Hodgkin's disease (PR-HD) have a dismal prognosis when treated with conventional salvage chemotherapy. We analyzed time to treatment failure (TTF), overall survival (OS) and clinical variables influencing the outcome in patients undergoing autologous stem cell transplantation (ASCT) for PR-HD and reported to the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO). PATIENTS AND METHODS: Sixty-two patients, 41 males and 21 females with a median age of 27 years (range 13-55) were analyzed. Forty-two patients (68%) had advanced stage at diagnosis, 47 (76%) presented with B symptoms and 29 (47%) with a bulky mediastinal mass. Seventy-five percent of the patients had received more than one line of therapy before ASCT. Thirty-three patients received bone marrow as a source of hematopoietic progenitors, and 29 peripheral blood. Six patients were conditioned with high-dose chemotherapy plus total-body irradiation and 56 received chemotherapy-based protocols. RESULTS: One-year transplantation-related mortality was 14% [95% confidence interval (CI) 6% to 23%]. Response rate at 3 months after ASCT was 52% [complete remission in 21 patients (34%), partial remission in 11 patients (18%)]. Actuarial 5-year TTF and OS were 15% (95% CI 5% to 24%) and 26% (95% CI 13% to 39%), respectively. The presence of B symptoms at ASCT was the only adverse prognostic factor significantly influencing TTF [relative risk (RR) 1.75, 95% CI 0.92-3.35, P = 0.08]. The presence of B symptoms at diagnosis (RR 2.08, 95% CI 0.90-4.79, P = 0.08), MOPP-like regimens as first-line therapy (RR 3.84, 95% CI 1.69-9.09, P = 0.001), bulky disease at ASCT (RR 2.79, 95% CI 0.29-6.03, P = 0.009) and two or more lines of therapy before ASCT (RR 2.24, 95% CI 0.95-5.27, P = 0.06) adversely influenced OS. CONCLUSIONS: In our experience, although overall results of ASCT in PR-HD patients are poor, one-quarter of the patients remain alive at 5 years. Despite this, other therapeutic strategies should be investigated in this group of patients to improve the outcome.
Assuntos
Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Transplante de Células-Tronco/estatística & dados numéricos , Adolescente , Adulto , Intervalos de Confiança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Fatores de Tempo , Transplante Autólogo , Resultado do TratamentoAssuntos
Doenças Autoimunes/terapia , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/métodos , Adulto , Artrite Reumatoide/terapia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/terapia , Proteínas Recombinantes , Espanha , Transplante de Células-Tronco/mortalidade , Condicionamento Pré-Transplante/métodosRESUMO
Nowadays, the chemoradiotherapeutic protocols for Hodgkin's disease (HD) achieve high curability rates. Hemato-oncologists focus on both avoiding medical and psychological sequelae of the treatment and returning patients to a normal life. The quality of life and psychological well-being of Spanish patients who are long-term survivors of HD were studied and compared to the results obtained from healthy controls. Questionnaires on quality of life [European Organization for Research and Treatment of Cancer (EORTC) QLQ30] and psychological status [hospital anxiety and depression (HAD) scale] were mailed to HD patients without active disease and free of second malignancies and were also given to healthy controls. Of 67 selected patients (68.6%), 46 were included in this study. The median follow-up for these 46 patients was of 7.6 years (0.8-22.1) after being diagnosed. Although there were no differences between patients and controls with regard to their global state of health and quality of life (72.9+/-22.7 vs 79.3+/-18.7; p=0.22), patients presented a lower physical function (88.2+/-18.1 vs 96.5+/-9.7; p=0.05) and a worse social operation scale (81.5+/-25.4 vs 96.3+/-13.1; p= 0.0015) together with higher symptoms of dyspnea (8.6+/-14.7 vs 0+/-0; p=0.03) and higher economic difficulties (23.1+/-38.3 vs 0.7+/-4.9; p=0.017) when compared with healthy controls. However, we did not find differences in the scores and the proportion of cases of anxiety and depression between the two groups. The quality of life questionnaire disclosed differences between patients and controls in some functional and symptomatic scales. These differences can be read as a consequence of either the disease itself or the treatment received. However, the results of this controlled pilot study should be confirmed in a larger series of Spanish HD survivors. In the future, these results could be a reference when new therapeutic protocols are designed to reduce the impact on the quality of life of the patients. Socioeconomic support to the patients should also be provided in order to improve their medical care.
Assuntos
Doença de Hodgkin/psicologia , Saúde Mental , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade , Estudos de Casos e Controles , Depressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Espanha , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The purpose of this study was to analyse the results and prognostic factors influencing overall survival (OS) and disease-free survival (DFS) in 452 patients diagnosed with diffuse large cell lymphomas (DLCL) treated with high-dose therapy (HDT) included in the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) Spanish registry. PATIENTS AND METHODS: At transplantation, median age was 42 years (range 15-73), 146 patients (32%) were transplanted in first complete remission (1st CR), 19% in second CR (2nd CR) and 47% had active disease: sensitive disease in 157 (35%) patients [95 were in first partial remission (1st PR) and 62 in second PR (2nd PR)] and refractory disease in 55 (12%) patients. Age-adjusted International Prognostic Index (IPI) was 2 or 3 in 51 patients (12%). Conditioning regimen consisted of BEAM (carmustine, etoposide, cytarabine and melphalan) in 39% of patients, BEAC (carmustine, etoposide, cytarabine and cyclophosphamide) in 33%, CBV (carmustine, etoposide and cyclophosphamide) in 10% and cyclophosphamide plus total body irradiation (TBI) in 12%. RESULTS: Estimated overall survival (OS) and disease-free survival (DFS) at 5 years were 53% and 43%, respectively. The transplant-related mortality was 11% (53 cases). By multivariate analysis three variables significantly influenced OS and DFS: number of protocols to reach 1st CR, disease status at transplant and TBI in the conditioning regimen. Age-adjusted IPI at transplantation also influenced OS. CONCLUSIONS: Prolonged OS and DFS can be achieved in patients with DLCL after HDT and our results suggest that the best line of chemotherapy should be used up-front in patients considered as candidates for HDT in order to obtain an early CR. Resistant patients are not good candidates for HDT and they should be offered newer strategies. Finally, polichemotherapy conditioning regimens offer better results compared with TBI.