RESUMO
We have studied a patient with a congenital bleeding disorder and phenotypic manifestations typical of Bernard-Soulier syndrome, including giant platelets with absent ristocetin-induced von Willebrand factor binding. Two monoclonal antibodies reacting with distinct epitopes in the amino-terminal domain of the alpha-chain of glycoprotein (GP) Ib were used to estimate the number of GP Ib molecules on the platelet membrane. In the patient, binding of one antibody (LJ-Ib10) was approximately 50% of normal, while binding of the other (LJ-Ib1) was absent. Binding of both antibodies was reduced to approximately 50% of normal in the mother and one sister of the propositus, and their platelets exhibited approximately 70% of normal von Willebrand factor binding. Immunoblotting studies confirmed the presence of GP Ib alpha, as well as GP IX, in patient platelets. Antibody LJ-Ib10, but not LJ-Ib1, could immunoprecipitate the patient's GP Ib alpha from surface-labeled proteins. Thus, platelets from the propositus contained a structurally and functionally altered GP Ib-IX complex lacking a specific antibody epitope and the ability to bind von Willebrand factor. In contrast, the binding of human alpha-thrombin to the patient's platelets was normal, and three classes of binding sites with high, intermediate, and low affinity could be detected. These studies define a distinct variant form of Bernard-Soulier syndrome and provide evidence, based on a naturally occurring mutant molecule, that the amino-terminal region of GP Ib alpha contains a von Willebrand factor-binding domain distinct from the high affinity thrombin-binding site. Use of different monoclonal antibodies with distinct epitope specificities appears to be essential for a correct identification of variant Bernard-Soulier syndrome.
Assuntos
Síndrome de Bernard-Soulier/fisiopatologia , Transtornos Plaquetários/fisiopatologia , Glicoproteínas da Membrana de Plaquetas/fisiologia , Anticorpos Monoclonais , Western Blotting , Epitopos , Humanos , Peso Molecular , Glicoproteínas da Membrana de Plaquetas/genética , Glicoproteínas da Membrana de Plaquetas/imunologia , Testes de Precipitina , Conformação Proteica , Trombina/metabolismo , Fator de von Willebrand/metabolismoRESUMO
This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiation-free, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninety-two untreated FL patients aged Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
, Transplante de Células-Tronco Hematopoéticas
, Linfoma Folicular/tratamento farmacológico
, Linfoma Folicular/mortalidade
, Adolescente
, Adulto
, Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
, Cisplatino/administração & dosagem
, Cisplatino/efeitos adversos
, Terapia Combinada
, Citarabina/administração & dosagem
, Citarabina/efeitos adversos
, Dexametasona/administração & dosagem
, Dexametasona/efeitos adversos
, Intervalo Livre de Doença
, Doxorrubicina/administração & dosagem
, Doxorrubicina/efeitos adversos
, Seguimentos
, Transplante de Células-Tronco Hematopoéticas/efeitos adversos
, Humanos
, Incidência
, Pessoa de Meia-Idade
, Recidiva Local de Neoplasia/mortalidade
, Prednisona/administração & dosagem
, Prednisona/efeitos adversos
, Fatores de Risco
, Análise de Sobrevida
, Resultado do Tratamento
, Vincristina/administração & dosagem
, Vincristina/efeitos adversos
, Irradiação Corporal Total
RESUMO
Fifty patients with recurrent Hodgkin's disease have been treated with high-dose therapy followed by autologous bone marrow transplantation. Forty-one patients had extranodal sites of relapse and 31 patients had constitutional symptoms. Two patients had been treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), lomustine, vinblastine, procarbazine, and prednisone (CcVPP), and radiation; 16 patients with MOPP, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), radiation, and lomustine, etoposide, and prednisone (CEP); 20 patients with alternating MOPP/ABVD, and 12 patients with alternating MOPP/ABVD followed by CEP and radiation. Eighteen patients had progressive disease during alternating MOPP/ABVD protocol alone or during conventional salvage therapy; 32 patients had had a complete remission with first-line therapy but later relapsed, 25 of them having received conventional salvage therapy; 12 achieved no response or progression ("resistant-relapse" patients); and 13 responded partially or completely ("sensitive-relapse" patients). Complete remission occurred in 24 patients (48%) with a median duration of 24 months and 16 patients (32%) achieved partial response with a median duration of 9 months, for an overall response rate of 80%. Ten patients failed to respond and died in progressive disease 1 to 10 months (median, 6 months) after transplantation. Toxicity was significant including infections (20%), liver enzymes and alkaline phosphatase elevations (100%), and carmustine lung toxicity (7%). There were two treatment-related deaths; one patient died of Pseudomonas aeruginosa septicemia and another patient died of cerebral hemorrhage. These results validate the procedure of high-dose therapy followed by autologous bone marrow transplantation in inducing remission in these advanced, highly-treated patients. Clearly, the question of whether high-dose therapy and transplantation will eventually supersede new conventional salvage therapies will be addressed after controlled clinical studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Doença de Hodgkin/tratamento farmacológico , Adulto , Bleomicina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Itália , Lomustina/administração & dosagem , Masculino , Mecloretamina/administração & dosagem , Prednimustina/administração & dosagem , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Transplante Autólogo , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
PURPOSE: The aim of our study was to compare in a multicentric randomized trial two regimens widely used in the treatment of advanced-stage intermediate- to high-grade non-Hodgkin's lymphoma and to assess whether a third-generation regimen (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) was superior to a second-generation regimen (procarbazine, methotrexate with leucovorin, doxorubicin, cyclophosphamide, and etoposide [ProMACE-MOPP]). PATIENTS AND METHODS: Between January 1987 and August 1991, 221 patients with diffuse intermediate- to high-grade non-Hodgkin's lymphoma (Working Formulation groups F, G, H, and K), stage II bulky (> 10 cm), III, or IV, were randomized by the Non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG) to receive ProMACE-MOPP for six cycles or MACOP-B for 12 weeks. Survival, progression-free survival, and disease-free survival were determined, and multivariate analysis of prognostic factors was performed. RESULTS: In the two groups of patients, there was no significant difference in terms of complete remission (CR) rate (49.1% with ProMACE-MOPP and 52.3% with MACOP-B), 3-year overall survival rate (45.2% with PROMACE-MOPP and 52.3% with MACOP-B), and 3-year progression-free survival rate (36.4% with ProMACE-MOPP and 36.1% with MACOP-B). In terms of toxicity, no significantly greater toxicity occurred in either arm. Overall toxicity was acceptable. The most frequent side effects were grade II through IV leukopenia, infection, mucositis, and anemia. Treatment-related deaths were equally distributed. CONCLUSION: No significant differences in terms of efficacy and/or toxicity between ProMACE-MOPP and MACOP-B are evident. These results are consistent with recent randomized trials showing that the new-generation aggressive regimens are no better than previous ones.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Leucovorina/administração & dosagem , Masculino , Mecloretamina/administração & dosagem , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
From January '85 to April '87, 81 patients (pts) with diffuse intermediate and high-grade non-Hodgkin's lymphomas were treated with the ProMace/MOPP protocol in a large Italian Cooperative Study Group (NHLCSG). Criteria for entry into the study included: no prior therapy, stage III-IV or stage II with bulky disease and/or B-symptoms, age below 65. 79 pts were evaluable for response. Almost all pts received six courses of chemotherapy, plus radiotherapy on bulky disease. 53 pts (67%) achieved complete remission (CR), 7 (9%) partial remission (PR), 4 (5%) were considered stable disease (SD) and 15 (19%) progression disease (PD) with 5 of them died early during treatment. The actuarial overall survival (OS) and disease free survival (DFS) are respectively 54% at 61 mos and 62% at 41 mos. The median follow-up from the end of therapy is 56 mos (range 40-68). Until now 20 pts (38%) relapsed on a median time of 8 mos (range 2-21) from CR. These data allowed to us to consider this regimen as effective as the third generation protocols also taking into account the multicenter basis of this study. With the aim to evaluate the impact of the third generation regimen on the outcome of these pts, a randomized study has been performed comparing ProMACE-MOPP with the third generation regimens MACOP-B. Therefore, from 1988 up to now, 206 pts with similar clinical and histological characteristics, have been enrolled in the two arms. No differences in terms of CR and DFS have been registered between the two treatments, with roughly the same toxicity. An analysis of prognostic factors in the larger series of pts treated with ProMACE-MOPP in the first and in the second study (167 pts) was performed. On these basis it seems reasonable that our next step would be to candidate these poor prognosis pts to a new therapeutic strategy which included the use of ABMT and/or PBSC transplantation as first line.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Mecloretamina/administração & dosagem , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Vincristina/administração & dosagemRESUMO
Fourty successive adult patients with lymphoblastic lymphoma entered a study of sequential chemotherapy consisting of an intensive LSA-L2-type protocol to induce first complete remission. Twenty-one patients in first CR (median age 24 years, range 15-43), after receiving a conditioning regimen consisting of cyclophosphamide and total body irradiation, underwent autologous bone marrow transplantation. At this time fourteen patients are alive and well 5-72 months post-transplant (median follow-up 58 months) with an actuarial disease free survival of 66%. These early results suggest that high-dose chemoradiotherapy followed by autologous bone marrow transplantation may improve long-term disease free survival in advanced stage adult lymphoblastic lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Transplante de Medula Óssea , Feminino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Estudos Prospectivos , Análise de SobrevidaRESUMO
OBJECTIVE: Purging procedures are increasingly used to provide stem cell collections devoid of contaminating tumor cells. In follicle center lymphoma (FCL), most approaches eradicate polymerase chain reaction (PCR);-detectable disease in only a fraction of harvests undergoing ex vivo manipulation. In this study we evaluated whether there is a relationship between tumor burden of stem cell harvests and successful clearance of PCR-detectable disease following ex vivo manipulation. MATERIALS AND METHODS: To address this issue, we developed a real-time PCR approach for quantitative measurement of tumor contamination using the bcl-2 rearrangement. Real-time PCR was used to evaluate the relationship between tumor burden of stem-cell harvests and purging effectiveness in PCR(+) samples derived from 10 FCL patients. Ex vivo purging was performed using the MaxSep cell separator (Baxter Immunotherapy, Deerfield, IL, USA). RESULTS: Our real-time PCR method proved effective, sensitive, accurate, and reproducible. Four collections were successfully cleared of minimal residual disease (MRD) whereas six remained PCR(+). Real-time PCR showed that the four collections successfully cleared of MRD had a prepurging tumor burden significantly lower than those remaining PCR(+) (p = 0.04). CONCLUSION: This study provides the first evidence that evaluation of tumor burden in stem-cell harvests by real-time PCR can predict the effectiveness of therapeutic intervention in non-Hodgkin's lymphoma. Based on these findings, we foresee a more widespread use of this technique to evaluate the impact of different therapeutic approaches in FCL.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Células-Tronco Hematopoéticas/citologia , Linfoma Folicular/sangue , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Sequência de Bases , Rearranjo Gênico , Gliceraldeído-3-Fosfato Desidrogenases/genética , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma Folicular/terapia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Neoplasia Residual/sangue , Proteínas Proto-Oncogênicas c-bcl-2/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Translocação Genética , Transplante AutólogoRESUMO
Alpha interferon has shown initial promise in the treatment of low-grade non-Hodgkin's lymphoma (NHL), especially with the nodular form of the disease. The present study enrolled 70 NHL patients who received either chlorambucil (CB; 10 mg/day) or CB plus interferon alfa-2b (5 million units (MU)/m2 subcutaneously three times a week). Among 63 evaluable patients, similar response rates (62.1% and 64.7% respectively) were recorded for the treatment arms. In patients receiving no maintenance therapy, those who received interferon alfa-2b during the induction phase showed a favourable trend in terms of incidence of relapse compared to those who had received chlorambucil alone. During maintenance therapy with interferon alfa-2b, no significant differences in the occurrence of relapse have yet been seen compared to patients on no maintenance therapy. A longer observation period is needed to make a definitive conclusion about the usefulness of interferon maintenance therapy and to evaluate further the effects of the combined schedule of chlorambucil and interferon induction on the duration of remission.
Assuntos
Clorambucila/uso terapêutico , Interferon-alfa/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Interferon alfa-2 , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Proteínas RecombinantesRESUMO
Twenty-eight patients with different hematological diseases (17 non-Hodgkin's lymphoma, one Hodgkin's disease and 10 multiple myeloma) underwent peripheral blood progenitor cell (PBPC) collection after cyclophosphamide 7 g/m2 and rh-G-CSF. Fifty-eight leukaphereses were carried out with a fully automated PBPC collection procedure. Progenitor cell release was monitored by standardized determination of CD34+ cells in the peripheral blood. After a profound aplasia, a continuous increase in CD34+ cells in the peripheral blood was seen for at least 3-4 days. In 82% of our patients more than 2.5 x 10(6) CD34/kg could be collected using a standard apheresis of 10 l. There was a high correlation between the CD34+ cells in the peripheral blood and CD34+ cells/kg harvested. (r2 = 0.91). A relatively constant ratio (median 14.3, range 3.2-22.6) was found between CD34+ cells/kg and CFU-GM/kg. Based on the CD34 values of the pre-apheresis blood and the body weight of an individual patient and using the mathematical model of regression analysis (y = mx + b) for the correlation between the CD34+ cells/microliter in the pre-apheresis blood and the CD34+ cells/kg, it was possible to create a formula allowing for target value tailored apheresis. Using this formula, the blood volume which needs to be processed in order to harvest a desired number of CD34+ cells/kg can be calculated. This strategy can be applied to reduce the time for and the number of aphereses. Nineteen leukaphereses were carried out applying the formula. In 18 of 19 leukaphereses the expected CD34+/kg values were correctly achieved or exceeded. The formula was most reliable when the CD34 value was higher than 15/microliter and when the WBC count was below 20 x 10(9)/l in the pre-apheresis blood. For mobilizations using hematopoietic growth factors alone our formula is not applicable, because in most cases the pre-apheresis white blood cell count is higher than 20 x 10(9)/l and the collection efficacy of lymphomonocytoid cells decreases with a high pre-apheresis white blood cell count. The formula also works with other mobilization regimens that induce a pronounced aplasia.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Leucaférese/métodos , Antígenos CD34/análise , Ciclofosfamida/uso terapêutico , Humanos , Proteínas RecombinantesRESUMO
Twenty successive adult patients with lymphoblastic lymphoma entered a study of sequential chemotherapy consisting of an intensive LSA2-L2-type protocol to induce first complete remission. Twelve patients in first CR (median age 22 years, range 15-43), after receiving a conditioning regimen consisting of cyclophosphamide and total body irradiation, underwent autologous bone marrow transplantation. Of these 12 patients at diagnosis, one was in stage III and 11 in stage IV; 11 showed mediastinal and seven showed bone marrow involvement. The transplant procedure was well tolerated and no treatment-induced deaths occurred. At this time nine patients are alive and well 25-44 months post-transplant (median follow-up 36 months) with an actuarial disease-free survival of 75%. These early results suggest that high-dose chemoradiotherapy followed by autologous bone marrow transplantation may improve long-term disease-free survival in advanced stage adult lymphoblastic lymphoma. In order to draw definite conclusions, however, a larger and randomized study is needed.
Assuntos
Transplante de Medula Óssea , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/radioterapia , Masculino , Estadiamento de Neoplasias , Projetos Piloto , Indução de Remissão , Transplante Autólogo , Irradiação Corporal TotalRESUMO
INTRODUCTION: Although definite risk classes are well known, risk-adapted modulation of first-line therapy is seldom attempted in adult ALL. So, a prospective validation of the therapeutic efficacy of a protocol (or a component thereof) in specific risk groups is uncommon. MATERIALS AND METHODS: From 1996-1999 a risk-oriented program (08/96) was evaluated in 102/121 unselected patients (median age 35 years, blast count 0-450 x 10(9)/l, 100 B(lin) (lineage), 21 T(lin)) responsive to induction therapy. The standard risk (SR) class was B(lin) CD10+ Ph- with blasts < 10 x 10(9)/l (prior studies: disease-free survival (DFS) rate 52% at five years with dose-intensive anthracycline-containing programs). The SR protocol was therefore anthracycline-rich (early consolidation cycles with total idarubicin 96 mg/m2), and comprised long-term maintenance. High-risk (HR) patients were eligible to the following three options: allogeneic hematopoietic stem cell transplantation (HSCT) from related family donor; short sequence with high-dose cyclophosphamide-cytarabine-methotrexate followed by melphalan/total body irradiation with autologous HSCT; or T(lin) ALL chemotherapy regimen inclusive of high-dose cytarabine and methotrexate. RESULTS: Treatment realization and three-year DFS rates according to risk class, HR subset and postremission treatment intensity were the following. SR group (n = 28): realization rate 93%, DFS 68.5%. HR group (n = 74): realization rate 80%, DFS 39% (P = 0.052 vs SR category). In HR group, three-year DFS rates by disease subtype were the following. B(lin) Ph- (n = 35) 43%; Ph+ (n = 19) 13% at 2.7 years (P = 0.006 vs other HR subtypes); T(lin) (n = 18) 59.5%. And DFS rates by treatment intensity were: allograft (n = 21) 40%; autograft (n = 28) 27%; shift to SR protocol (n = 13) 52% (P = ns vs allograft/autograft); T(lin) program (n = 10) 57%. Matched analyses of treatment protocols and disease subtypes suggested a possible therapeutic role of the autograft regimen in B(lin) Ph- ALL with a blast count < 25 x 10(9)/l, and of T(lin) protocol for T(lin) ALL. Comparisons with retrospective control cohorts were confirmatory of anthracycline activity in SR subclass. CONCLUSION: The intended strategy was applicable to the majority of study patients, confirming the value of anthracyclines in SR class and, preliminarily, the usefulness a T(lin)-specific treatment. Apart from the case of Ph+ ALL, the indications for high-dose procedures with HSCT remains largely undetermined in this study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Idoso , Antineoplásicos/administração & dosagem , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Idarubicina/administração & dosagem , Masculino , Melfalan/administração & dosagem , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Fatores de Risco , Transplante Homólogo , Irradiação Corporal TotalRESUMO
Reinfusion of myeloma progenitor cells may contribute to relapse of multiple myeloma after autologous stem cell transplantation. The aim of our study was to investigate whether monoclonal B-cells are present in the apheresis product and to evaluate the clinical relevance of these cells. Leukapheresis products of 55 patients were purged with anti-B-cell-Monoclonal antibodies (MoAbs) and immunobeads. Monoclonal B-cells were found in 85% of patients within the B-cell population. In one third of all myeloma patients, the majority of B-cells was represented by monoclonal myeloma progenitor B-cells, whereas in two thirds of patients monoclonal cells only represented a small part of the entire B-cell population. As shown by sequence analysis, monoclonal precursor B-cells and malignant plasma cells had the identical genetic CDR III sequence. The purging efficacy, using a negative selection system, was a median of 3 logs (range 1,5-3,5). No statistical difference in the purging efficacy was found when 3, 4 or 5 MoAbs against B-cells antigens were used. However, a tumor specific signal could be detected in the purged harvest of all patients, when the highly sensitive ASO-PCR approach was used. Furthermore, we found a direct correlation between the amount of remaining monoclonal cells after negative selection and the event free survival of myeloma patients. 10/15 patients with a median of 20 x 10(3) monoclonal cells in the purged product relapsed at a median of 1,4 years, whereas only 6/24 patients with an oligoclonal pattern including a low number of remaining monoclonal cells relapsed at a median of 2,2 years. The event free survival (EFS) was statistically different between the two groups (p = 0,014).
Assuntos
Anticorpos Monoclonais/sangue , Linfócitos B/imunologia , Imunoglobulinas/análise , Mieloma Múltiplo/terapia , Proteínas do Mieloma/análise , Adulto , Anticorpos Monoclonais/uso terapêutico , Linfócitos B/patologia , Purging da Medula Óssea/métodos , Regiões Determinantes de Complementaridade/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/imunologia , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Prognóstico , Resultado do TratamentoRESUMO
Here we report the results of a randomised multicenter phase III clinical trial which assesses the therapeutic efficacy and tolerability of a chemotherapy protocol CEMP (cyclophosphamide, etoposide, mitoxantrone and prednisone) in adult and elderly patients with advanced intermediate and high-grade NHL. Between October 1991 and October 1995, 139 patients, aged 55 to 79 years, with diffuse intermediate and high-grade lymphoma, were enrolled. A considerable percentage of patients had clinically aggressive disease: 32.4% had systemic symptoms, 79% had stage III or IV disease, 33.8% had bone marrow involvement, 46% had splenic involvement and 42.5% had increased values of serum lactate dehydrogenate. Complete remission was achieved in 70 of the 139 patients (51.9%) and PR in 12 (16.6%) with an overall response of 68.5%. The overall response survival rate at 6 years was 39%, whereas DFS rate was 48.7% and PFS rate was 28.5%. At four years 49% of the patients were still in CR. Dividing the patients in two groups, under and over 65 years of age, we obtained the same results as far as overall response is concerned. No toxic deaths occurred, neither cardiac, renal nor liver complications happened. CEMP regimen is an effective and safe protocol with good results in elderly people, well comparable to those achieved in younger ones.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Análise Atuarial , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Ciclofosfamida/administração & dosagem , Ciclofosfamida/normas , Ciclofosfamida/toxicidade , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/normas , Etoposídeo/toxicidade , Feminino , Humanos , Linfoma não Hodgkin/complicações , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/normas , Mitoxantrona/toxicidade , Prednisona/administração & dosagem , Prednisona/normas , Prednisona/toxicidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Three cases of an unusual form of suppurative chronic otitis media in children 2 and 3 years old are presented. The clinical feature common to all cases was otorrhea, beginning at the first months of life, with a silent evolution to a complete peripheral facial paralysis. In one case the facial paralysis was bilateral. The treatment applied was surgical: subtotal petrosectomy. The surgical findings were bloody granulation tissue, sequestering completely the otic capsule. The facial nerve was destroyed almost the total length of the Fallopian canal in all cases. The histopathologic examination revealed a destructive and nonspecific chronic inflammatory process. The culture showed Gram-negative organisms, such as Pseudomonas aeruginosa and Proteus mirabilis. Etiologic aspects involved in the process are discussed and the name non-specific necrotizing petrositis is suggested to individualize this rare form of otitis which, with morbidity, leads to severe complications such as facial paralysis and deafness.
Assuntos
Osteíte/etiologia , Otite Média Supurativa/complicações , Otite Média/complicações , Osso Petroso , Pré-Escolar , Surdez/etiologia , Nervo Facial/patologia , Paralisia Facial/etiologia , Feminino , Tecido de Granulação/patologia , Humanos , Masculino , Osteíte/patologia , Osteíte/cirurgia , Osteotomia , Otite Média Supurativa/patologia , Otite Média Supurativa/cirurgia , Osso Petroso/patologia , Osso Petroso/cirurgia , Proteus mirabilis/isolamento & purificação , Pseudomonas aeruginosa/isolamento & purificação , Terminologia como AssuntoRESUMO
The authors report two cases of malignant external otitis in infant boys, 5 and 6 months old respectively, caused by different etiologic agents (Pseudomonas aeruginosa and Proteus mirabilis). Both of them were in very poor general health, but neither developed complications such as facial paralysis because of the intensive treatment that was employed from the beginning.
Assuntos
Otite Externa/diagnóstico , Infecções por Proteus/diagnóstico , Infecções por Pseudomonas/diagnóstico , Humanos , Lactente , Masculino , Otite Externa/tratamento farmacológico , Otite Externa/etiologia , Proteus mirabilis , Infecções por Pseudomonas/tratamento farmacológicoRESUMO
Invasive fungal infections (IFIs) still pose major challenges in allogeneic hematopoietic SCT (HSCT), and effective antifungal prophylaxis remains a matter of debate. The aim of this retrospective study was to evaluate the toxicity and the impact of aerosolized deoxycholate amphotericin B (aero-d-AmB) on respiratory tract IFIs (airways IFIs) in a homogeneous cohort of allogeneic HSCT patients, transplanted at one institution. Since 1999, 102 consecutive patients were transplanted from matched related (N = 71) or unrelated donor (MUD). Aero-d-AmB was administered for a median time of 16 days (range 2-45), in addition to systemic antifungal prophylaxis. Prolonged administration was neither associated with increased severe bacterial infections, nor with severe adverse events. In 16 patients in whom aero-d-AmB was delivered for less than 8 days, due to worsened clinical conditions or poor compliance, proven or probable airways IFIs were diagnosed in three cases (one mucormycosis and one fusariosis and one probable aspergillosis), whereas in 84 patients receiving aero-d-AmB for ≥ 8 days, one possible and one probable aspergillosis were diagnosed. A shortened administration (< 8 days) of aero-d-AmB was therefore associated with an increased risk of both total airways IFIs (P = 0.027) and proven/probable IFIs (P = 0.012). At multivariate analysis prolonged aero-d-AmB administration retained an independent protective effect on airways IFIs (P = 0.026) whereas a MUD transplant was associated with a borderline increase of IFIs risk (P=0.052). Overall, 95.1% of patients did not experience airways IFIs and no patient died due to IFIs. In this cohort of patients, prolonged aero-d-AmB seems to have a role in preventing respiratory tract IFIs, but a randomized controlled trial is recommended to verify the impact of this prophylaxis in the setting of allogeneic HSCT.