RESUMO
The 3 main types of cardiac amyloidosis are linked to two protein precursors: AL amyloidosis secondary to free light chain deposits in the context of monoclonal gammopathy (mainly of undetermined significance or myeloma) and transthyretin amyloidosis (ATTR), comprising wild-type transthyretin amyloidosis (ATTRwt for wild type) and hereditary transthyretin amyloidosis (ATTRv for variant). These diseases are underdiagnosed and highly prevalent in common cardiac phenotypes in recent studies (heart failure with preserved ejection fraction, severe aortic stenosis, hypertrophic cardiomyopathy). Myocardial amyloid infiltration affects all cardiac structures and clinically promotes predominantly heart failure, conductive disorders and cardioembolic events. The search for extracardiac signs makes it possible to arouse diagnostic suspicion. Electrocardiogram, echocardiography and cardiac MRI can suspect cardiac amyloidosis. The diagnostic confirmation follows a simple algorithm including a systematic search for monoclonal gammapathy and a disphosphonate scintigraphy. Histological proof is necessary in case of AL or ATTR amyloidosis with concomitant monoclonal gammopathy in order to initiate specific treatment. Due to the late disease onset in ATTRv, genetic testing must be routine in all cases of ATTR. These diseases are no longer perceived as incurable since recent therapeutic innovations. A better knowledge of the disease is more than ever necessary.
Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Insuficiência Cardíaca , Amiloidose de Cadeia Leve de Imunoglobulina , Gamopatia Monoclonal de Significância Indeterminada , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/terapia , Cardiomiopatias/diagnóstico , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/diagnósticoRESUMO
This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Terapia de Salvação/métodos , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação/mortalidade , Análise de Sobrevida , Transplante AutólogoRESUMO
BACKGROUND: There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. AIM: To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. METHODS: In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). RESULTS: After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P < 0.001). No toxicity-related death was reported. CONCLUSIONS: The use of anti-cancer systemic therapy is safe and efficient in gastric MALT lymphoma. In this retrospective study, the combination of rituximab plus chlorambucil seems more efficient than rituximab or alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Intervalo Livre de Doença , Feminino , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Rituximab , Neoplasias Gástricas/patologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Central nervous system (CNS) relapse is an uncommon but dramatic complication of diffuse large B-cell lymphoma (DLBCL). Several studies have demonstrated the superiority of cerebrospinal fluid (CSF) flow cytometry (FCM), as compared with conventional cytology (CC), in detecting occult leptomeningeal disease. The clinical relevance of a positive FCM still has to be clarified. PATIENTS AND METHODS: We analyzed CSF from 114 DLBCL patients at diagnosis (n = 95) or at relapse (n = 19) by FCM and CC. Most patients received meningeal prophylaxis. FCM results did not influence treatment strategies. RESULTS: Fourteen samples were FCM+, versus one CC+ (also FCM+). Within all patients without neurological symptoms (n = 101), four (4%) relapsed in the CNS, with a median time to relapse of 5.2 months. Only one-fourth (25%) was FCM+ before relapse. More than one extranodal disease site and elevated lactate dehydrogenase levels were associated with an increased risk of CNS relapse. CONCLUSIONS: FCM gives far more positive results than CC. However, a positive FCM result did not translate into a significant increase in CNS relapse rate in this histologically uniform population receiving CNS prophylaxis.
Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Citometria de Fluxo/métodos , Imunofenotipagem/métodos , Linfoma Difuso de Grandes Células B/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/secundário , Citodiagnóstico/métodos , Feminino , Humanos , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva , Adulto JovemRESUMO
This retrospective analysis investigated the prognostic value of del(13) and t(4;14) abnormalities and the impact of prior treatment on outcomes in 207 heavily pretreated patients with relapsed or refractory multiple myeloma (MM) treated with lenalidomide plus dexamethasone. Patients with relapsed or refractory MM who had either earlier received thalidomide or bortezomib, or for whom continuation of these agents was contraindicated, and who had fluorescence in situ hybridization data available were included in the analysis. Patients with relapsed or refractory MM who received treatment with lenalidomide plus dexamethasone in the presence of del(13) and t(4;14) chromosomal abnormalities had lower overall response rates (ORRs) and shorter median progression-free survival (PFS) and overall survival (OS) compared with those who did not have these abnormalities. The results also showed that prior treatment with bortezomib was associated with shorter median PFS and OS. Progression during thalidomide therapy was the only significant independent predictor for OS and that the presence of del(13) and hemoglobin levels <10 g per 100 ml were prognostic factors for ORR and PFS, but not OS, in these heavily pretreated relapsed or refractory MM patients treated with lenalidomide plus dexamethasone.
Assuntos
Aberrações Cromossômicas , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Borônicos/uso terapêutico , Bortezomib , Quimioterapia Combinada , Feminino , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Análise Multivariada , Modelos de Riscos Proporcionais , Pirazinas/uso terapêutico , Estudos Retrospectivos , Talidomida/administração & dosagem , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
Internal hernias, including paraduodenal (traditionally the most common), pericecal, foramen of Winslow, and intersigmoid hernias, account for approximately 0.5-5.8% of all cases of intestinal obstruction and are associated with a high mortality rate, exceeding 50% in some series. We report an extremely rare case of an internal abdominal hernia, through the right mesocolon, in a young woman with a right colon with no peritoneal fixation. This hernia was revealing by abdominal pain, nausea, and vomiting. The diagnosis of internal hernia was suggested by computed tomography (CT), but the exact type of internal hernia was confirmed by surgical exploration. The postoperative course was uneventful and the patient fully recovered after 3 days. The patient is free from symptoms and from recurrence, after 12 months of follow-up.
Assuntos
Hérnia Abdominal/complicações , Obstrução Intestinal/etiologia , Adulto , Feminino , Hérnia Abdominal/diagnóstico por imagem , Hérnia Abdominal/cirurgia , Humanos , Obstrução Intestinal/cirurgia , Intestino Delgado , Mesocolo/patologia , Mesocolo/cirurgia , Tomografia Computadorizada por Raios XRESUMO
UNLABELLED: The electrophysiological evaluation of Wolff-Parkinson-White syndrome (WPW) is recommended in children aged more than five years to detect a risk of life-threatening arrhythmia. The purposes of the study were to determine the feasibility of transesophageal EPS in a child between six and 10 years in out-patient clinic. METHODS: Electrophysiological study (EPS) was indicated in 22 children, aged six to 10 years, with a manifest WPW either for no documented tachycardia (n=7), unexplained dizziness (n=2) or for a sportive authorization in 10 asymptomatic children. Two of the last children had a history of permanent tachycardia after the birth but were asymptomatic since the age of one year without drugs. RESULTS: EPS was performed in all children. The main difficulty lied in passing the catheter through the mouth. Programmed stimulation at cycle length of 380 ms was performed in all children to avoid high rates of pacing when the conduction through the accessory pathway (AP) and normal AV system was evaluated. Isoproterenol was not required in five children, because they developed a catecholaminergic sinus tachycardia. The AP refractory period was determined in all children between 200 and 270 ms. Orthodromic reentrant tachycardia (RT) was induced in 11 children, three asymptomatic children (27%), seven complaining of tachycardia and one with syncope. Rapid antidromic tachycardia was induced in this last child with dizziness. Atrial fibrillation was never induced. CONCLUSIONS: Esophageal EPS can be performed without sedation in a young child six to 10-year-old with a shortened protocol of stimulation, which was capable to clearly evaluate the WPW-related risks.
Assuntos
Sedação Consciente , Técnicas Eletrofisiológicas Cardíacas/métodos , Sistema de Condução Cardíaco/fisiopatologia , Síndrome de Wolff-Parkinson-White/diagnóstico , Síndrome de Wolff-Parkinson-White/fisiopatologia , Criança , Pré-Escolar , Estudos de Viabilidade , Humanos , Pacientes AmbulatoriaisRESUMO
Simultaneous cardiac and renal involvement is associated with a particularly poor prognosis in patients with AL amyloidosis (AL-A). We report the first case of a successful long-term outcome of combined heart and kidney transplantation not followed by autologous stem cell transplantation in a patient with systemic AL-A. The recipient was a 46-year-old man with end-stage renal failure associated with serious cardiac involvement in the context of AL-A. Before transplantation, two courses of oral melphalan plus prednisone induced partial hematologic remission, as shown by the decrease in circulating free light chain with no improvement of renal or heart function. The patient underwent combined heart and kidney transplantation as a rescue treatment. During the follow-up period (36 months), plasma cell dyscrasia remains in complete remission, with normal free lambda light chain levels and no recurrence of amyloid deposition on heart and kidney grafts. This case report demonstrates that combined heart and kidney transplantation not systematically associated with stem cell transplantation may be considered an additional therapeutic option in AL-A patients with severe organ dysfunction and partial hematologic remission.
Assuntos
Amiloidose/cirurgia , Transplante de Coração , Transplante de Rim , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
BACKGROUND: Revised response criteria for aggressive lymphomas have been proposed (Cheson, J Clin Oncol, 2007) stressing the role of (18)fluorodeoxyglucose-positron emission tomography (PET) in posttreatment evaluation. The value of PET after four cycles compared with the International Workshop Criteria (IWC) remains to be established. PATIENTS AND METHODS: In all, 103 patients with untreated diffuse large B-cell lymphoma were prospectively enrolled to evaluate the prognostic impact of PET after two and four cycles. RESULTS: Median age was 53 years (19-79), 68% male. The International Prognostic Index was low=22%, low-intermediate=19%, intermediate-high=33% and high risk=26%. Treatment consisted of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) (30%) or dose-intensified CHOP (70%), with rituximab (49%) or without (51%). Ninety-nine patients were evaluated by PET and IWC at four cycles: 77 (78%) had a negative PET, while 22 (22%) remained positive. The 5-year event-free survival (EFS) was 36% for patients with a positive PET versus 80% with a negative examination, whatever the response [complete response (CR) versus partial response (PR)] according to IWC (P<0.0001). Positive PET patients had a 5-year EFS of 58% if in CR/CR unconfirmed by IWC and 0% if not (P<0.0001). The same observations could be made in patients treated with and without rituximab. CONCLUSION: The integration of PET in treatment evaluation offers a powerful tool to predict outcome.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Estudos Prospectivos , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/uso terapêuticoRESUMO
BACKGROUND: High-dose therapy (HDT) with stem-cell support is the reference treatment for relapsed lymphoma, but is not appropriate for all patients. Conventional salvage chemotherapies have been used with limited efficacy and significant toxicity. Rituximab, gemcitabine and oxaliplatin are active as single agents in relapsed or refractory lymphoma, and have demonstrated synergistic effects in vitro and in vivo. PATIENTS AND METHODS: Forty-six patients with relapsed or refractory B-cell lymphoma received up to eight cycles of R-GemOx (rituximab 375 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) and oxaliplatin 100 mg/m(2) on day 2). The majority (72%) had diffuse large B-cell lymphoma. RESULTS: After four cycles of R-GemOx, the overall response rate was 83% [50% complete response (CR)/unconfirmed CR (CRu)]. High CR/CRu rates were observed in all histological subtypes. In patients who had previously received rituximab, the CR/CRu rate after eight cycles was 65%. The 2-year event-free and overall survival rates (median follow-up of 28 months) were 43% and 66%, respectively. Among responders, the probability of being disease free for 2 years was 62%. Treatment was generally well tolerated. CONCLUSION: R-GemOx shows promising activity with acceptable toxicity in patients with relapsed/refractory B-cell lymphoma who are not eligible for HDT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Rituximab , Terapia de Salvação/métodos , Taxa de Sobrevida , GencitabinaRESUMO
BACKGROUND: Rituximab induces clinical response in advanced B-cell lymphoma and is efficient in removing circulating B-cell from peripheral blood. We therefore postulated that rituximab might be a useful in vivo purging agent before high-dose therapy in this setting. PATIENTS AND METHODS: Fourteen patients with relapsed follicular, marginal zone and mantle cell lymphomas (11, two and one cases, respectively) and a PCR-detectable molecular marker were treated first with rituximab, then a mobilization chemotherapeutic regimen, followed by high-dose therapy with peripheral blood stem cell transplantation. PCR analyses were performed in peripheral blood before rituximab and during follow-up, and in harvest. RESULTS: Harvests were free of PCR-detectable molecular marker in nine of the 11 studied cases (82%). After high-dose therapy, clinical complete remission was obtained in 13 (93%) patients and molecular remission in 11 (79%). With a median follow-up of 3 years, the 14 transplanted patients were alive, 11 of them remaining in clinical complete remission and eight in molecular remission at last follow-up. CONCLUSION: Rituximab treatment followed by high dose therapy appears to be effective in achieving complete clinical and molecular response. In vivo harvest purging is predictive of prolonged clinical and molecular remission.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Purging da Medula Óssea/métodos , Linfoma de Células B/terapia , Linfoma Folicular/terapia , Linfoma de Célula do Manto/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Anticorpos Monoclonais Murinos , Antígenos CD34/metabolismo , Terapia Combinada , Feminino , Seguimentos , Mobilização de Células-Tronco Hematopoéticas , Humanos , Linfoma de Células B/patologia , Linfoma Folicular/patologia , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Indução de Remissão , Rituximab , Terapia de Salvação , Células-Tronco/patologia , Transplante Autólogo , Resultado do TratamentoRESUMO
PURPOSE: Because it is unclear whether T-cell/histiocyte-rich large B-cell lymphomas (H/TCRBCL) should be considered as a true clinicopathologic entity, we conducted a matched-control analysis comparing patients with H/TCRBCL and patients with diffuse large-B cell lymphoma (B-DLCL). PATIENTS AND METHODS: More than 4,500 patients were enrolled onto non-Hodgkin's lymphoma trials conducted by the Groupe d'Etude des Lymphomes de l'Adulte. After histologic review, 50 patients were subclassified as H/TCRBCL. They were matched to 150 patients with B-DLCL for each of the factors of the International Prognostic Index (IPI). RESULTS: Clinical characteristics of H/TCRBCL patients showed a male predominance and a median age of 47 years. Performance status was normal in 89% of patients, whereas lactate dehydrogenase level was increased in 60% of patients. The disease was disseminated in 81% of patients, and 48% had two or more involved extranodal sites. The IPI score was >or= 2 in 53% of patients. The complete response rate to chemotherapy was 63%, and 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- SD) were 58% +/- 18% and 53% +/- 16%, respectively. The matched-control analysis showed a trend toward a better response to chemotherapy for patients with B-DLCL (P =.06), whereas no difference was observed in OS (P =.9) and EFS (P =.8). CONCLUSION: H/TCRBCL is an aggressive disease that often presents with adverse prognostic factors. However, when treatment is adapted to the disease risk, outcome is equivalent to that observed in patients with B-DLCL. Thus H/TCRBCL should be considered a pathologic variant that belongs to the B-DLCL category.
Assuntos
Histiócitos/patologia , Linfoma de Células B/classificação , Linfoma Difuso de Grandes Células B/classificação , Linfócitos T/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/mortalidade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Monofosfato de Citidina/análogos & derivados , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Arabinonucleotídeos/administração & dosagem , Monofosfato de Citidina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide de Fase Crônica/mortalidade , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Recombinantes , Fatores de Risco , Taxa de SobrevidaRESUMO
We report a case of autologous hematopoietic recovery with durable leukemic remission after BMT from a phenotypically HLA-identical donor in a 30-year-old male with CML. Graft loss was diagnosed from day 60 post-BMT by VNTR PCR. To assess for the presence of a minor donor-derived T cell population that could exert an anti-leukemic effect, we serially applied a sensitive process of chimerism analysis by fluorescent PCR on sorted T cells. No residual donor T cells could be detected. We also showed retrospectively that a very sensitive method of MRD analysis by real-time quantitative PCR could have permitted prediction of relapse in this case.
Assuntos
Transplante de Medula Óssea , Medula Óssea/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Subpopulações de Linfócitos T/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Medula Óssea/química , Sobrevivência Celular , Terapia Combinada , DNA de Neoplasias/genética , Proteínas de Fusão bcr-abl/análise , Proteínas de Fusão bcr-abl/genética , Sobrevivência de Enxerto , Humanos , Hidroxiureia/administração & dosagem , Interferon-alfa/administração & dosagem , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide de Fase Crônica/patologia , Leucemia Mieloide de Fase Crônica/terapia , Masculino , Repetições Minissatélites , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasia Residual , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , RNA Mensageiro/genética , Indução de Remissão , Terapia de Salvação , Sensibilidade e Especificidade , Condicionamento Pré-TransplanteRESUMO
BACKGROUND: The MINE regimen (mitoguazone, ifosfamide, vinorelbine and etoposide) is a salvage chemotherapy for relapsed and refractory Hodgkin's disease. CASE REPORTS: We report the cases of a 16-year-old girl and a 17-year-old boy who had Hodgkin's disease and developed painful and massive subcutaneous inflammatory edema after MINE chemotherapy. Morphine was unable to control pain leading to major functional disability of joint movement. One patient had an elevated creatine kinase level, hypoalbuminemia, hypodermic and muscular edema at magnetic resonance imaging and diffuse hemorrhagic hypodermic edema at skin biopsy. The other patient was found to have only hypoalbuminemia. The clinical course was favorable in both cases within a few weeks, but with recurrent episodes of pain and localized areas of fat necrosis five months later in one case. DISCUSSION: This side effect of MINE chemotherapy - subcutaneous inflammatory edema, myalgia and skin pain - has not been described previously for the different components of the regimen. Three clinicopathological hypotheses could be put forward: capillary leak syndrome, panniculitis, toxic fasciitis. The causal drug remains undetermined, but the most likely would be vinorelbine because of the chronology of the eruptions during the first and last days of chemotherapy and because of the known vascular toxicity of vinorelbine which could explain a capillary leak syndrome.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Edema/induzido quimicamente , Etoposídeo/efeitos adversos , Doença de Hodgkin/tratamento farmacológico , Ifosfamida/efeitos adversos , Mitoguazona/efeitos adversos , Vimblastina/efeitos adversos , Adolescente , Biópsia , Síndrome de Vazamento Capilar/induzido quimicamente , Creatina Quinase/sangue , Edema/complicações , Edema/metabolismo , Edema/patologia , Necrose Gordurosa/induzido quimicamente , Feminino , Humanos , Inflamação , Imageamento por Ressonância Magnética , Masculino , Dor/induzido quimicamente , Recidiva , Vimblastina/análogos & derivadosRESUMO
PURPOSE: To compare changes in gadolinium enhancement at magnetic resonance (MR) imaging with outcome in mediastinal lymphoma after treatment. MATERIALS AND METHODS: Thirty-one patients with bulky mediastinal lymphoma (17 with Hodgkin disease, 14 with non-Hodgkin lymphoma) underwent serial MR imaging before and up to 50 months after treatment, with routine follow-up (including computed tomography). Signal intensity ratios between masses and muscle were calculated on T1-weighted, T2-weighted, and contrast material-enhanced T1-weighted spin-echo MR images. The percentage enhancement and signal intensity ratios of mediastinal masses on T2-weighted MR images were calculated at diagnosis and during and after treatment. RESULTS: Twenty-one patients with persistent complete remission had a mean percentage enhancement of residual masses (4%; range, -26% to 40%) that was significantly lower than that of initial masses (78%; range, 41%-124%). Although the mean signal intensity ratio of residual masses on T2-weighted images was significantly lower than that of initial masses, an increase in this ratio was observed in four patients after treatment. In seven patients with relapse, the percentage enhancement value of the residual mass was as high as that of the initial mass. CONCLUSION: Gadolinium enhancement of lymphomatous masses of the mediastinum decreased markedly after treatment in patients in continuous complete remission but not in patients with relapse.
Assuntos
Doença de Hodgkin/patologia , Linfoma não Hodgkin/patologia , Imageamento por Ressonância Magnética , Neoplasias do Mediastino/patologia , Adulto , Terapia Combinada , Meios de Contraste , Feminino , Seguimentos , Gadolínio , Doença de Hodgkin/terapia , Humanos , Linfoma não Hodgkin/terapia , Masculino , Neoplasias do Mediastino/terapia , Meglumina , Neoplasia Residual , Compostos Organometálicos , Estudos Prospectivos , Fatores de TempoRESUMO
We have expressed human p53 cDNA in the yeast Saccharomyces cerevisiae and shown that the level of production and the length of the p53 protein depends on the presence of untranslated mRNA regions (UTRs). The expression of the ORF alone leads to a p53 protein of correct size (53 kDa) that accumulates to high levels, concomitantly with the presence of a small amount of a p40 protein (40 kDa). However, when either the entire 5'-UTR and a part of the 3'- or 5'-UTR alone is used, this leads to the production of small amounts of the 40 kDa truncated form only. The p40 protein corresponds to a truncated form of p53 at the C-terminal extremity since it reacts only with a monoclonal antibody recognising the N-terminal epitope. This effect on the amount and length of p53 protein had no correlation at the mRNA level, suggesting that translational control probably occurs through the 5'-UTR. We propose a model of structural interaction between this UTR and a part of the ORF mRNA for the regulation of p53 expression in this heterologous context.
Assuntos
Regiões 5' não Traduzidas/genética , Fases de Leitura Aberta/genética , Saccharomyces cerevisiae/genética , Proteína Supressora de Tumor p53/genética , Regiões 3' não Traduzidas/genética , Northern Blotting , Western Blotting , Divisão Celular/genética , DNA Complementar/genética , Regulação da Expressão Gênica , Humanos , Plasmídeos/genética , Biossíntese de Proteínas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimento , Deleção de Sequência , Transcrição Gênica , Proteína Supressora de Tumor p53/metabolismoRESUMO
PURPOSE: In the previous LNH87-2 study, consolidative high-dose therapy followed by stem cell transplantation (HDT) improved disease-free survival, as well as survival for patients (pts) presenting with two or three factors of the age-adjusted international prognostic index (Aa-IPI) in first complete remission (CR). In order to improve further the outcome of such patients, we conducted a pilot study of consolidative tandem autotranplant. PATIENTS AND METHODS: Thirty-six patients (pts) under 60 years of age with two or three factors of the Aa-IPI were enrolled. Their main characteristics were: diffuse large B-cell lymphoma (83%), Aa-IPI three factors (50%), and marrow involved (36)%. The procedure consisted of 1) induction with four cycles of ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) 2) in responding pts, peripheral blood stem cell (PBSC) collection after the fourth cycle of ACVBP (11 pts) or after an additional mobilization regimen (Cyclophosphamide-VP16) (17 pts) 3) a first HDT (mitoxantrone, cyclophosphamide, VP16 and carmustine) followed by PBSC infusion 4) a second HDT (busulfan, carboplatin and melphalan) followed by PBSC infusion. Among the 29 patients responding to induction, 28 received the first HDTand 24 the second. RESULTS: The rates of three-year-event free survival and survival are 47% (95% confidence interval (95% CI: 31%-63%) and 50% (95% CI: 37%-69%), respectively. Eighteen patients remained free of evolutive disease and 18 patients have died, 15 from disease progression and three from treatment-related toxicity after tandem transplant (two veno-occlusive disease and one cerebral toxoplasmosis). CONCLUSION: We conclude that tandem transplant did not improve the results of the LNH87-2 study in which patients received a single consolidative HDT.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Difuso de Grandes Células B/terapia , Condicionamento Pré-Transplante , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Projetos Piloto , Prednisona/uso terapêutico , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Linfócitos T/metabolismo , Transplante Autólogo , Resultado do Tratamento , Vindesina/uso terapêuticoRESUMO
PURPOSE: To identify the prognostic factors that influence overall survival (OS) in patients with stage III-IV follicular lymphomas and evaluate the clinical usefulness and the prognostic value of the International Prognostic Index (IPI). PATIENTS AND METHODS: Four hundred eighty-four patients with Ann Arbor stage III-IV follicular lymphomas treated in two phase III trials from 1986 to 1995 were screened for this study. All histologic slides were reviewed by two hematopathologists. The influence of the initial parameters on survival was defined by univariate (log-rank test) and multivariate (Cox model) analyses. RESULTS: The poor prognostic factors for OS (age > 60 years, "B" symptom(s), > or = two extranodal sites, stage IV disease, tumor bulk > 7 cm, at least three nodal sites > 3 cm, liver involvement, serous effusion-compression or orbital/epidural involvement, and erythrocyte sedimentation rate > 30 mm/h) that were significant in univariate analysis were subjected to multivariate analysis. Three factors remained significant: B symptom(s) (risk ratio = 1.80), age greater than 60 years (risk ratio = 1.60), and at least three nodal sites greater than 3 cm (risk ratio = 1.71). When the IPI was applied to these patients, the score was 1, 2, 3, and 4-5 in 49%, 39%, 11%, and 2%, respectively, and it was significant for progression-free survival (P =.002) and OS (P =.0001). CONCLUSION: Three prognostic factors for poor OS were identified: B symptoms, age greater than 60 years, and at least three nodal sites greater than 3 cm. The IPI was prognostic for OS, but in this population, a very low number of patients belonged to the high-risk groups.