RESUMO
In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.
Assuntos
Biomarcadores Tumorais/análise , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/diagnóstico , Segunda Neoplasia Primária/classificação , Segunda Neoplasia Primária/diagnóstico , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Segunda Neoplasia Primária/terapia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The benefit of azacitidine treatment in survival of high-risk myelodysplastic syndromes (MDS) patients compared with conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival (OS) between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and acute myeloblastic leukemia (AML) progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8-16) months for azacitidine-treated patients and 12.2 (11-14.1) for patients under CCT (P=0.41). In a multivariate model, age, International prognostic scoring system and lactate dehydrogenase were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86-1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend toward a better survival was observed in azacitidine-treated patients (median survival 13.3 (11-18) months) compared with CCT (median survival 8.6 (5-10.4) months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etiologia , Masculino , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Prognóstico , Sistema de Registros , Espanha/epidemiologia , Resultado do TratamentoRESUMO
The aim of this study was to analyse the effect of glucocorticoid therapy (GCCT) on Wnt signalling antagonists (sclerostin and Dkk-1) and their relationship with bone turnover. 25 patients (8 M/17 F, aged 48±19yrs) recently initiating GCCT (≥7.5mg/day, ≤6months) were prospectively included. Bone turnover markers (bone formation: P1NP, osteocalcin [OC], bone ALP; bone resorption: sCTx) and Wnt antagonists (serum sclerostin and Dkk-1) were assessed in all patients (short-term and 12months after initiating GCCT). Bone mineral density (BMD) was performed to assess osteoporosis. The results were compared with 60 healthy controls. At short-term patients on GCCT showed a significant decrease in bone formation markers versus controls (P1NP: 19±9 vs. 43±16ng/mL, p<0.001; OC: 7.4±2.4 vs. 18.4±5.2ng/mL, p=0.001) and in Dkk-1 levels (24.5±20.1 vs. 36.8±13.7pmol/L, p=0.008) with similar sclerostin values (41.8±21.8 vs. 42.1±13.9pmol/L, p=0.950). Sclerostin correlated positively with GCCT doses (r=0.449, p=0.024) and lumbar BMD (r=0.424, p=0.035), and negatively with bone ALP (r=-0.398, p=0.049). A progressive decrease in Dkk-1 levels was observed at 12months, (19.1±14.9, p=0.001), whereas sclerostin increased compared to controls (48.9±11.6, p=0.045). In conclusion, the effect of GCCT on the serum levels of the Wnt signalling parameters differs depending on the antagonist evaluated. Whereas sclerostin values increased and showed a relationship with the dose and bone AP, Dkk-1 levels decreased throughout the study suggesting a counter-regulatory mechanism of this factor thereby reducing the deleterious effect of GCCT in the bone.
Assuntos
Densidade Óssea/efeitos dos fármacos , Proteínas Morfogenéticas Ósseas/metabolismo , Glucocorticoides/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Osteogênese/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The severity of neutropenia in myelodysplastic syndrome (MDS) has not been completely studied. We analyzed the prognostic significance of severe neutropenia (neutrophils count <0.5×10(9)/L) at diagnosis in 1109 patients with de novo MDS and low/intermediate-1 IPSS included in the Spanish MDS Registry. Severe neutropenia was present at diagnosis in 48 of 1109 (4%). Patients with severe neutropenia were most strongly represented within the groups of refractory cytopenia with multilineage dysplasia (40%) and refractory anemia with excess of blast type 1 (29%). Severe neutropenia had negative effects on the low/intermediate-1 risk group. A significant difference in overall survival was observed between patients with severe neutropenia (28 months) and patients with a neutrophil count higher than 0.5×10(9)/L (66 months) (p<0.0001). Also, severe neutropenia predicted a significantly reduced on leukemia-free survival (p<0.0001). In the multivariate analysis, severe neutropenia retained its independent prognostic influence on overall survival [HR: 2.19, 95% CI (1.41-3.10), p<0.0001] and leukemia free survival [HR: 3.51, 95% CI (1.97-6.26), p<0.0001]. The degree of neutropenia should be considered as additional prognostic factor in low/intermediate-1 IPSS MDS.
Assuntos
Anemia Refratária/complicações , Síndromes Mielodisplásicas/complicações , Neutropenia/diagnóstico , Neutropenia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Estadiamento de Neoplasias , Neutropenia/mortalidade , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: High-dose chemotherapy (HDT) followed by autologous stem-cell transplantation (ASCT) is considered the gold standard in the treatment of patients with relapsed or refractory Hodgkin's lymphoma (HL). However, the optimal salvage regimen has not yet been established. PATIENTS AND METHODS: We retrospectively analyzed the efficacy and toxicity of MINE (mesna, ifosfamide, mitoxantrone, and etoposide) alternated with ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in the treatment of 61 relapsed or refractory HL patients after ABVD-based chemotherapy. RESULTS: Overall, 25 patients (41%) achieved a complete response (CR), 23 (38%) a partial response (PR), 4 (7%) a stable disease, and 8 (13%) progressed for an overall response rate of 79%. Response to first-line chemotherapy was the most important prognostic factor for response to MINE-ESHAP (P = 0.041). No grade 4 extrahematologic toxic effects or toxic deaths were observed. Adequate peripheral blood stem-cell collection was achieved in 56 of 59 (95%) mobilized patients. Overall survival and event-free survival after HDT and ASCT were significantly higher for patients achieving CR/PR in comparison with those refractory to MINE-ESHAP (46% and 35% versus 74% and 69%, respectively). CONCLUSION: MINE-ESHAP results in a high response rate with acceptable toxicity in patients with HL having failed ABVD-based treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/terapia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Cisplatino/administração & dosagem , Terapia Combinada , Citarabina/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mitoguazona/administração & dosagem , Periodicidade , Prednisona/administração & dosagem , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Transplante Autólogo , Falha de Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Adulto JovemRESUMO
BACKGROUND: Different prognostic scores have been proposed to predict the outcome of follicular lymphoma (FL) patients at diagnosis. A new prognostic index specifically addressing FL patients, the Follicular Lymphoma International Prognostic Index (FLIPI), has recently been developed, which might also be useful in patients with progression. PATIENTS AND METHODS: One hundred and three patients (55 male, 48 female; median age 59 years) with FL in first relapse/progression after an initial response to therapy (50 complete responders/ 53 partial responders) were included in the study. RESULTS: Five-year survival from progression (SFP) was 55% (95% confidence interval 44%-66%). The distribution according to the FLIPI at relapse was 39% good prognosis, 24% intermediate prognosis and 37% poor prognosis. Five-year SFP for these groups were 85%, 79% and 28%, respectively (P < 0.0001). Other variables at relapse with prognostic significance for SFP were age, presence of B symptoms, performance status, bulky disease, number of involved nodal sites, lactate dehydrogenase level, hemoglobin level, histological transformation, the Italian Lymphoma Intergroup prognostic index for FL and the International Prognostic Index for aggressive lymphomas. In the multivariate analysis bulky disease (P=0.01), presence of B symptoms (P=0.03) and FLIPI at relapse (P=0.0003) were the most important variables for predicting SFP. CONCLUSIONS: In patients with FL at first relapse/progression, the FLIPI, along with the presence of bulky disease and B symptoms, are features that predict SFP and thus could be useful to select candidates for experimental treatments.
Assuntos
Linfoma Folicular/classificação , Linfoma Folicular/patologia , Estadiamento de Neoplasias/métodos , Fatores Etários , Idoso , Progressão da Doença , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Recidiva , Análise de SobrevidaRESUMO
We report the identification of a new DRB1* allele in a Spanish Caucasoid family during a search for a histocompatible bone marrow donor. This novel allele, designated as DRB1*1145, differs from DRB1*1123 in one nucleotide at position 199 in exon 2 (A replacing T), leading to one amino acid change from phenylalanine (Phe) to isoleucine (Ile) at codon 67. The propositus's father had identical class II alleles but showed a minor mismatch at locus B (B*4403 by B*4402) and a C-locus mismatch (Cw*1502 by Cw*0501). We discuss the criteria of selecting a non-related bone marrow donor with a minor mismatch on the DRB1* allele or the related father having a minor mismatch at B locus and a C-locus mismatch.
Assuntos
Transplante de Medula Óssea , Antígenos HLA-DR/genética , Polimorfismo Genético , Alelos , Sequência de Aminoácidos , Família , Feminino , Cadeias HLA-DRB1 , Humanos , Masculino , Dados de Sequência Molecular , População Branca/genéticaRESUMO
PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS: Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS: Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P =.01). The 5-year overall survival (OS) was 36%. Age (< 60 v > or = 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P =.04). CONCLUSION: Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/radioterapia , Irradiação Craniana/métodos , Linfoma/radioterapia , Análise Atuarial , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carmustina/administração & dosagem , Doenças do Sistema Nervoso Central/etiologia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Terapia Combinada , Irradiação Craniana/efeitos adversos , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma/tratamento farmacológico , Linfoma/mortalidade , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Espanha/epidemiologia , Taxa de Sobrevida , Reino Unido/epidemiologia , Vincristina/administração & dosagemRESUMO
T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-resistant malignancy with a median survival of 7.5 months. Preliminary results indicated a high remission induction rate with the human CD52 antibody, CAMPATH-1H. This study reports results in 39 patients with T-PLL treated with CAMPATH-1H between March 1993 and May 2000. All but 2 patients had received prior therapy with a variety of agents, including 30 with pentostatin; none achieved complete remission (CR). CAMPATH-1H (30 mg) was administered intravenously 3 times weekly until maximal response. The overall response rate was 76% with 60% CR and 16% partial remission (PR). These responses were durable with a median disease-free interval of 7 months (range, 4-45 months). Survival was significantly prolonged in patients achieving CR compared to PR or no response (NR), including one patient who survived 54 months. Nine patients remain alive up to 29 months after completing therapy. Seven patients received high-dose therapy with autologous stem cell support, 3 of whom remain alive in CR 5, 7, and 15 months after autograft. Stem cell harvests in these patients were uncontaminated with T-PLL cells as demonstrated by dual-color flow cytometry and polymerase chain reaction. Four patients had allogeneic stem cell transplants, 3 from siblings and 1 from a matched unrelated donor. Two had nonmyeloablative conditioning. Three are alive in CR up to 24 months after allograft. The conclusion is that CAMPATH-1H is an effective therapy in T-PLL, producing remissions in more than two thirds of patients. The use of stem cell transplantation to consolidate responses merits further study.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia Prolinfocítica de Células T/tratamento farmacológico , Leucemia Prolinfocítica/tratamento farmacológico , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/efeitos adversos , Antineoplásicos/efeitos adversos , Terapia Combinada , Análise Citogenética , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunofenotipagem , Leucemia Prolinfocítica/mortalidade , Leucemia Prolinfocítica/terapia , Leucemia Prolinfocítica de Células T/mortalidade , Leucemia Prolinfocítica de Células T/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Taxa de Sobrevida , Transplante HomólogoRESUMO
Thalidomide is active in patients with refractory myeloma. Seventeen patients (nine men/eight women, median age 73 years) with multiple myeloma (MM) were treated with thalidomide. Fifteen patients had refractory disease and two untested relapse. The median dose of thalidomide was 500 mg (range, 200-800 mg). Nine of the 17 patients (53%) responded. The response rate was significantly higher in patients with no extramedullary disease than in those with soft tissue masses (75% CI: 43-95% versus 0%; P = 0.01)). Of note, no decrease in the size of soft tissue plasmacytomas was observed in all the five patients who had extramedullary involvement. This data suggests that the mechanism of action and effectiveness of thalidomide might depend on the site of the tumour cells.
Assuntos
Imunossupressores/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Proteínas Musculares , Plasmocitoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Talidomida/uso terapêutico , Idoso , Células da Medula Óssea/patologia , Conectina , Esquema de Medicação , Feminino , Humanos , Masculino , Mieloma Múltiplo/patologia , Mieloma Múltiplo/urina , Proteínas do Mieloma/urina , Plasmócitos/patologia , Plasmocitoma/patologia , Plasmocitoma/urina , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/urina , Falha de TratamentoRESUMO
BACKGROUND: Combination chemotherapy, including hybrid regimens, is the standard treatment for patients with advanced Hodgkin disease (HD). Although a prolonged complete response (CR) is achieved in up to 70-80% of patients, long term complications, such as secondary leukemia, are of concern. Cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (C-MOPP/ABV) is a hybrid chemotherapy in which cyclophosphamide is substituted for mechlorethamine, an agent that has been implicated as the cause of secondary malignancies. METHODS: Seventy-three patients (37 males and 36 females; median age, 35 years) diagnosed with Stage III or IV HD or Stage II with bulky disease, B-symptoms, elevated erythrocyte sedimentation rate, or hilar adenopathy were treated with 8 courses of C-MOPP/ABV at a single institution during a 6-year period. Radiotherapy (RT) was administered when bulky disease or residual masses were present. Endpoints of the study were response to therapy, failure free survival (FFS), overall survival (OS), and toxicity. RESULTS: Sixty-five patients (90%) received the 8 planned courses, with 49 of them (70%) receiving the full prescribed doses. After chemotherapy, 57 patients (78%) reached CR. Seven additional patients who achieved partial response (PR) reached CR after complementary radiotherapy, with an overall CR rate of 88%. The median follow-up was 31 months. Twelve patients relapsed; the 4-year FFS was 66% (95% CI, 54-78%). Two patients died during treatment because of sepsis and four due to disease progression. The 4-year OS was 92% (95% CI, 86-98%). Age > 60 years and bone marrow involvement were related to severe infectious complications. No late toxicity was reported. CONCLUSIONS: C-MOPP/ABV induces CR with acceptable toxicity in a high proportion of advanced HD patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Intervalos de Confiança , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Radioterapia Adjuvante , Indução de Remissão , Taxa de Sobrevida , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
BACKGROUND: Identification of RBC pyruvate-kinase (PK) gene mutations by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) followed by PK gene sequencing in positive cases has been assessed and the results obtained with a preliminary study of 15 unrelated patients of Spanish origin are presented. PATIENTS AND METHODS: Patients have been classified into two different groups: group 1, propositus (15 cases), and group 2, relatives of the patients included in group 1 (10 males and 5 females). In group 1, a PCR was followed by SSCP and sequencing, and in group 2, the PCR was followed by digestion with specific restriction endonucleases (PCR-ER). RESULTS: Group 1: from 15 patients included in the study 2 were identified as homozygous, 4 as heterozygous and 9 as compound heterozygous. In this group, were identify 26 affected alleles with 11 different mutations: T1456 10 alleles (38.6%), T721 3 alleles (11.6%), A1010, C514, C1015 and T1223 2 alleles (7.7%), and C1070, A1291, T1508, A1595 y T1675 one allele. Relatives from 8 out of 15 patients from group 1 showed the following pattern: homozygous (one case), heterozygous (10 cases), compound heterozygous (2 cases) and normal (2 cases). CONCLUSIONS: SSCP procedure followed by direct gene sequencing in positive cases is fast and simple enough to allow the identification of PK deficient variants, avoiding the need of biochemical characterisation of semipurified deficient enzyme, which is more cumbersome and time consuming. In addition, the PCR-ER method is a very useful tool for screening of the most frequent molecular variants, as well as, for the detection of the carrier condition of this enzymopathy (family studies).
Assuntos
Anemia Hemolítica/genética , Eritropoese/genética , Piruvato Quinase/deficiência , Piruvato Quinase/metabolismo , Aminoácidos/genética , Anemia Hemolítica/enzimologia , Doença Crônica , Feminino , Genótipo , Hematologia , Humanos , Masculino , Nucleotídeos/genética , Mutação Puntual/genética , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Análise de Sequência de DNA , Sociedades Médicas , EspanhaRESUMO
BACKGROUND: Several studies have shown the potential advantages laparoscopic splenectomy (LS) over open surgery. The aim of this study has been to evaluate the advantages of LS over open surgery in the treatment of autoimmune thrombocytopenia. PATIENTS AND METHODS: 54 consecutive patients splenectomized for the treatment of idiopathic thrombocytopenic purpura (ITP) or HIV-related thrombocytopenia were analyzed. Operative features (operative time, conversion to open surgery, accessory spleens), immediate (stay, analgesia and blood transfusion requirements) and late postoperative features (platelet count), as well as splenectomy-related complications in both surgical procedures were compared. RESULTS: Between February 1990 and February 1997, 54 splenctomies were performed for the treatment of autoimmune thrombocytopenia (ITP, n = 47, and HIV-related thrombocytopenia, n = 7). Eighteen were performed through an open approach, and 36 by laparoscopy. Both groups were comparable with regard to age, sex, platelet count, disease duration and body mass index. LS was completed in 34 cases (conversion to open surgery: 5.5%). The incidence of accessory spleens was 11% in the LS group and 5.5% in the open surgery group. Postoperative morbidity (16% vs 28%) and blood requirements (25% vs 33%) were lower after LS, but the differences did not reach statistical significance. Analgesia requirements (7 [SD 3] vs 11 [6]; p < 0.01) and postoperative stay (3.8 [2.6] vs 7.4 [3] days; p < 0.01) were significantly shorter after LS. Following splenectomy, the platelet counts became normal in 72% of patients submitted to LS and 78% of patients in the open surgery group. After 20 and 63 months mean follow-up, one patient in each group developed late complications. CONCLUSION: As compared to open surgery, LS offers a better immediate clinical outcome, with similar long-term results.
Assuntos
Laparoscopia , Púrpura Trombocitopênica Idiopática/cirurgia , Esplenectomia/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The PK-LR gene has been studied in 12 unrelated patients with red cell pyruvate kinase deficiency and hereditary nonspherocytic haemolytic anaemia (CNSHA). The entire codifying region of the R-type PK gene and the flanking intronic regions were analysed by single-stranded conformation polymorphism (SSCP) followed by direct sequencing of abnormal DNA. 10 different mutations were identified in 22/24 alleles at risk. Eight of these were missense mutations that caused the following single amino acid changes: G514C (172Glu-Gln), G1010A (337Arg-Gln), G1015C (339Asp-Gln), T1070C (357Ile-Thr), C1223T (408Thr-Ile), G1291A (431Ala-Thr), C1456T (486Arg-Trp) and G1595A (532Arg-Gln). Two were nonsense mutations: G721T (241Glu-Stop) and C1675T (559Arg-Stop). 7/22 alleles demonstrated the same C1456 --> T mutation. The study of the polymorphic site at nucleotide (nt) 1705 performed in all cases disclosed a 1705 C/C mutation in 10 and a 1705 A/C mutation in three. This is the first report on the presence of several different L-type PK gene mutations within Spanish population. Furthermore, from the PK gene mutations found, six were unique and not previously described (1015C, 1070C, 1223T, 1291A, 1595A and 1675T) and one (C1456T) seems to be predominant in Spain. Interestingly, no case with the 1529A mutation commonly found in Northern European populations was present here.
Assuntos
Anemia Hemolítica Congênita não Esferocítica/genética , Piruvato Quinase/genética , Adolescente , Adulto , Anemia Hemolítica Congênita não Esferocítica/sangue , Anemia Hemolítica Congênita não Esferocítica/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Piruvato Quinase/deficiência , Análise de Sequência de DNA , EspanhaRESUMO
Patients with diffuse large-cell lymphoma (DLCL) achieve a complete response (CR) in most cases, but at least one-third of them eventually relapse. Such an event occurs most frequently within 2 yr from CR achievement. The aim of the present study was to analyse the risk and pattern of relapse of patients with DLCL in CR. One hundred and three patients with DLCL (53 male/50 female; median age: 55 yr) in CR after doxorubicin-containing first-line treatments were included in the study. Main clinicobiological characteristics at diagnosis and at relapse were analysed. Uni- and multivariate studies were performed. Forty-one patients (40%) eventually relapsed, in 27 cases within 2 yr from CR and 14 thereafter. Histological subtype was the same at diagnosis and at relapse in all the early relapsing patients and in 8 of 10 late relapsing patients with available biopsy. The most important variables at diagnosis for predicting relapse were advanced stage (p<0.01) and bone marrow infiltration (p=0.05), with stage (I-II vs. III-IV) (p=0.009; relative risk=2.28) being the only predictive variable in the multivariate analysis. No differences were found according to the treatment given. The second CR rate obtained in the late relapsing patients after salvage therapies was higher that in early relapsing (50% vs. 37%). Median survival from relapse was 1.4 yr for patients early relapsing and it was not achieved for those with late relapses (p=0.09). Late relapse is a quite common event in DLCL lymphomas, with those patients achieving more frequently a second CR and having better survival than early relapsed patients.
Assuntos
Linfoma Difuso de Grandes Células B/prevenção & controle , Linfoma Difuso de Grandes Células B/terapia , Idoso , Doxorrubicina/uso terapêutico , Feminino , Técnicas Histológicas , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Fatores de TempoRESUMO
Pyoderma gangrenosum is a neutrophilic dermatosis that is frequently associated with malignancies such as myeloproliferative disorders. The development of this dermatologic disorder is thought to be mediated by immunological mechanisms. A case of pyoderma gangrenosum associated with the administration of alpha2b-interferon (alpha2b-IFN) in a patient with chronic granulocytic leukemia is described. Discontinuation of alpha2b-IFN and the administration of cyclosporin A and prednisone resulted in cure of the pyoderma gangrenosum. Serum levels of tumor necrosis factor, interleukin-6 and soluble interleukin-2 receptor increased when the cutaneous lesions appeared and returned to normal levels when the lesion healed. We believe that this is the first reported case of pyoderma gangrenosum associated with alpha2b-IFN therapy.