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1.
Ann Oncol ; 22(4): 939-946, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20935058

RESUMO

BACKGROUND: Explore safety and efficacy of three palonosetron-containing regimens for emesis prevention over 7 days in multiple myeloma (MM) patients receiving melphalan (100 mg/m(2)) and hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: Randomized, double-blind pilot study in MM patients (n=73) receiving 1, 2, or 3 days of 0.25 mg palonosetron (30-s i.v. bolus) 30 min before melphalan (days -2 and -1) and HSCT (day 0). Patients received dexamethasone (20 mg i.v., days -2 and -1) immediately before or after study drug/placebo. Daily diaries recorded emesis, rescue medication, nausea duration, and adverse events (AEs). RESULTS: Seven-day complete protection (no emesis) occurred in 41.7% [95% confidence interval (CI) 22.1% to 63.4%], 41.7% (95% CI 22.1% to 63.4%), and 44.0% (95% CI 24.2% to 65.1%) of patients receiving 1, 2, or 3 days of palonosetron, respectively (P=0.43). Complete response (emesis free without rescue medication) occurred in 8.3%, 20.8%, and 20.0% (P=0.14). Common AEs (≥10%) were mild-to-moderate diarrhea, constipation, headache, insomnia, and flatulence. No serious AEs occurred. CONCLUSIONS: Palonosetron with dexamethasone was safe and effective in preventing emesis in MM patients receiving melphalan and HSCT. This pilot study with a limited number of patients suggests that multiple doses of palonosetron could be more effective than a single dose in making patients emesis free without need for rescue medication. However, even multiple doses of palonosetron resulted in only 20% of patients being emesis free without rescue medication, suggesting that further improvement will require development of more effective combination antiemetic therapy.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Isoquinolinas/uso terapêutico , Melfalan/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Náusea/prevenção & controle , Quinuclidinas/uso terapêutico , Vômito/prevenção & controle , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Isoquinolinas/administração & dosagem , Isoquinolinas/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/cirurgia , Náusea/induzido quimicamente , Palonossetrom , Quinuclidinas/administração & dosagem , Quinuclidinas/efeitos adversos , Vômito/induzido quimicamente
2.
Bone Marrow Transplant ; 38(9): 585-92, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16953209

RESUMO

Multiple myeloma is a disease of the elderly. Survival outcomes remain unacceptably low in older adults with multiple myeloma. To date, no obvious difference in tumor biology has been elucidated to explain the survival disparity between older and younger patients. Multiple factors including comorbidity, performance status, decreased physiologic reserve and potentially undertreatment contribute to poor outcomes in elderly patients with multiple myeloma. High-dose chemotherapy with autologous stem cell transplantation (ASCT) is increasingly being used to treat elderly patients with multiple myeloma in an effort to improve survival outcomes. Recent case comparison studies, and preliminary transplant registry data suggest that selected older patients can be treated with high-dose chemotherapy effectively with similar toxicity and survival benefits compared to younger patients. Traditional upper age limits for autologous transplantation are being challenged along with the definition of 'elderly' itself. Ultimately, the role of high-dose chemotherapy with stem cell rescue in the upfront treatment of older adults with multiple myeloma can only be established by prospective randomized trials. In the process of designing studies to investigate the use of ASCT in older patients, multiple issues unique to the elderly population will need to be considered. First, it will be critical to develop and validate patient selection algorithms that incorporate measures of comorbidity, cognitive function, physiologic reserve and psychosocial function to identify patients most likely to tolerate and benefit from ASCT. Second, preparative and conditioning regimens will need to be further tailored to maximize the benefit to risk ratio. Finally, outcome measures in clinical trials should include disability and quality of life measures, which may be equally important in making treatment decisions for older patients. The future application and study of autologous transplantation in older patients with multiple myeloma provides a unique opportunity to challenge ageism and serve as a model for development of tailored assessments and interventions in this population.


Assuntos
Envelhecimento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/terapia , Transplante de Células-Tronco , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Células-Tronco/mortalidade , Transplante Autólogo
3.
Cancer Res ; 46(12 Pt 1): 6481-8, 1986 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3096564

RESUMO

We have correlated immunological characteristics and karyotypic abnormalities from lymphomas in 118 patients. T-lymphomas differed significantly from B- and non-B-, non-T-lymphomas in having more normal metaphases, trisomy 19, and breaks at 1q21, 2q21, 3q27, 4q21, and 17q21 (P less than or equal to 0.03). Non-T-lymphomas had breaks in 18q in one-half the cases, but only one of 11 T-lymphomas had such breaks (P = 0.02). Among B-lymphomas, specific chromosome abnormalities were associated with the type of immunoglobulin heavy but not light chain expressed. A break at 14q22 or q24 was associated with surface delta mu-immunoglobulin (P = 0.02); trisomy 22 or a break in 22q and a break at 2q32 was associated with surface gamma-immunoglobulin (P less than 0.001); and trisomy 12 and a break at 2p13 was associated with cytoplasmic gamma-immunoglobulin (P less than 0.01). Among B-lymphomas, several cytogenetic abnormalities were associated (P less than or equal to 0.02) with expression of CD24 or CD9 surface antigens. Lack of CD24 was associated with breaks in 2p25, 5q, and 6q21; CD9 was associated with a break at 6q15. Associations with a specific immunological phenotype were not identified for cytogenetic abnormalities involving a band to which genes encoding immunoglobulin or the T-cell receptor have been localized. Breaks were common at 14q32, the genomic site of the immunoglobulin heavy chain loci, in B-, non-B-, non-T-, and T-lymphomas. In T-lymphomas this may be because this is the site of the AKT1 oncogene. Breaks were uncommonly found at the light chain loci or the genomic sites encoding the T-cell receptor. However, the recurring breakpoints associated with T-lymphomas were commonly found on chromosomes to which genes coding for various T-cell antigens have recently been provisionally assigned.


Assuntos
Aberrações Cromossômicas , Linfoma/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Diferenciação de Linfócitos T , Antígenos de Superfície/análise , Criança , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 2 , Feminino , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Imunoglobulinas/genética , Cariotipagem , Linfoma/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores de Antígenos de Linfócitos B/análise , Receptores de Antígenos de Linfócitos T/genética , Trissomia
4.
J Clin Oncol ; 5(9): 1348-55, 1987 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3305794

RESUMO

Forty remission patients with high-risk acute lymphoblastic leukemia (ALL) underwent matched allogenic bone marrow transplantation (BMT) following preparation with cyclophosphamide and fractionated total body irradiation (TBI). As of March 1987, the median follow-up is more than 3 1/2 years. Thirteen patients are alive (11 relapse free) between 2 and 4 1/2 years post-BMT. Neither age, sex, remission number, prior extramedullary leukemia, nor WBC at diagnosis of ALL was statistically significant as a predictor of relapse-free survival. The development of acute graft-v-host disease (GVHD) in 17 patients was found, with time-dependent Cox regression analysis, to be associated with a significant reduction in post-BMT relapse risk (P = .04) and improved disease-free survival (P = .11). A prospective, randomized trial of maintenance chemotherapy with oral methotrexate and mercaptopurine did not demonstrate improvement in relapse risk or survival for those assigned maintenance chemotherapy (P = .7). These results suggest that allogeneic BMT can result in extended relapse-free survival for some patients with high-risk ALL. More effective preparative chemoradiotherapy and exploitation of the apparent graft-v-leukemia effect may be useful in future trials.


Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro , Leucemia Linfoide/terapia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Leucemia Linfoide/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão
5.
J Clin Oncol ; 14(2): 572-8, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8636773

RESUMO

PURPOSE: To determine the outcome of HLA-identical sibling bone marrow transplants in advanced Hodgkin's disease. PATIENTS AND METHODS: We reviewed the data on 100 consecutive patients with Hodgkin's disease who received HLA-identical sibling bone marrow transplants between April 1, 1982 and August 12, 1992, reported to the International Bone Marrow Transplant Registry (IBMTR). The median interval from diagnosis to transplant was 2.5 years (range, < 1 to 14). All had advanced disease. Eighty-nine of 100 patients were not in remission at the time of transplant. Fifty had pretransplant Karnofsky scores less than 90% and 27 had active infection in the week before transplant. Patients received a variety of conditioning regimens; 45 received total-body radiation. RESULTS: The 100-day probability of acute graft-versus-host disease (GVHD) was 35% (95% confidence interval [CI], 26% to 46%); the 3-year probability of chronic GVHD was 45% (95% CI, 31% to 59%). The 3-year probability of relapse was 65% (95% CI, 50% to 78%). The 3-year probability of survival was 21% (95% CI, 14% to 30%). The 3-year disease-free survival rate was 15% (95% CI, 9% to 24%). CONCLUSION: HLA-identical sibling bone marrow transplants have a limited role in advanced Hodgkin's disease.


Assuntos
Transplante de Medula Óssea , Antígenos HLA/análise , Doença de Hodgkin/terapia , Adolescente , Adulto , Criança , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Histocompatibilidade , Doença de Hodgkin/mortalidade , Humanos , Masculino , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento
6.
Genetics ; 144(3): 1075-85, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8913751

RESUMO

Previous work has shown that mutation of the gene that encodes the microtubule motor subunit kinesin heavy chain (Khc) in Drosophila inhibits neuronal sodium channel activity, action potentials and neurotransmitter secretion. These physiological defects cause progressive distal paralysis in larvae. To identify the cellular defects that cause these phenotypes, larval nerves were studied by light and electron microscopy. The axons of Khc mutants develop dramatic focal swellings along their lengths. The swellings are packed with fast axonal transport cargoes including vesicles, synaptic membrane proteins, mitochondria and prelysosomal organelles, but not with slow axonal transport cargoes such as cytoskeletal elements. Khc mutations also impair the development of larval motor axon terminals, causing dystrophic morphology and marked reductions in synaptic bouton numbers. These observations suggest that as the concentration of maternally provided wild-type KHC decreases, axonal organelles transported by kinesin periodically stall. This causes organelle jams that disrupt retrograde as well as anterograde fast axonal transport, leading to defective action potentials, dystrophic terminals, reduced transmitter secretion and progressive distal paralysis. These phenotypes parallel the pathologies of some vertebrate motor neuron diseases, including some forms of amyotrophic lateral sclerosis (ALS), and suggest that impaired fast axonal transport is a key element in these diseases.


Assuntos
Axônios/metabolismo , Proteínas de Ligação ao Cálcio , Drosophila/genética , Cinesinas/genética , Paralisia/etiologia , Animais , Animais Geneticamente Modificados , Axônios/patologia , Axônios/ultraestrutura , Transporte Biológico , Moléculas de Adesão Celular Neuronais/metabolismo , Drosophila/metabolismo , Feminino , Proteínas de Choque Térmico HSP40 , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Doença dos Neurônios Motores/metabolismo , Doença dos Neurônios Motores/patologia , Mutagênese , Proteínas do Tecido Nervoso/metabolismo , Organelas , Paralisia/genética , Fenótipo , Terminações Pré-Sinápticas , Proteínas Qa-SNARE , Coelhos , Sinaptotagminas
7.
Genetics ; 142(1): 195-204, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8770597

RESUMO

To investigate the possibility that kinesin transports vesicles bearing proteins essential for ion channel activity, the effects of kinesin (Khc) and ion channel mutations were compared in Drosophila using established tests. Our results show that Khc mutations produce defects and genetic interactions characteristic of paralytic (para) and maleless (mle) mutations that cause reduced expression or function of the alpha-subunit of voltage-gated sodium channels. Like para and mle mutations, Khc mutations cause temperature-sensitive (TS) paralysis. When combined with para or mle mutations, Khe mutations cause synthetic lethality and a synergistic enhancement of TS-paralysis. Furthermore, Khc: mutations suppress Shaker and ether-a-go-go mutations that disrupt potassium channel activity. In light of previous physiological tests that show that Khc mutations inhibit compound action potential propagation in segmental nerves, these data indicate that kinesin activity is required for normal inward sodium currents during neuronal action potentials. Tests for phenotypic similarities and genetic interactions between kinesin and sodium/potassium ATPse mutations suggest that impaired kinesin function does not affect the driving force on sodium ions. We hypothesize that a loss of kinesin function inhibits the anterograde axonal transport of vesicles bearing sodium channels.


Assuntos
Transporte Axonal/genética , Drosophila/genética , Cinesinas/genética , Mutação , Animais , Cruzamentos Genéticos , Drosophila/metabolismo , Feminino , Genes de Insetos , Masculino , Paralisia/genética , Canais de Potássio/genética , Canais de Potássio/metabolismo , Canais de Sódio/genética , Canais de Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , Temperatura
8.
Leukemia ; 9(5): 770-3, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7769838

RESUMO

6-Thioguanine (6-TG) was administered as a continuous i.v. infusion for 7 days to 24 patients with relapsed or refractory acute leukemia or in the blast phase of chronic granulocytic leukemia. The daily dose of 6-TG was escalated from 37.5 mg/m2 to 160 mg/m2. Stomatitis was dose-related and dose-limiting with a maximum tolerated dose of 120 mg/m2 daily. Cutaneous reactions were dose-related but not dose-limiting. The recommended dose for phase II trials in acute leukemia is 120 mg/m2 per day as a continuous infusion for 7 days. There were two complete and four partial remissions among all patients. At the suggested phase II dose of 120 mg/m2 there were two complete remissions and one partial remission in five evaluable patients.


Assuntos
Crise Blástica/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Tioguanina/administração & dosagem , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Tioguanina/efeitos adversos
9.
J Natl Cancer Inst Monogr ; (19): 41-4, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7577204

RESUMO

The prognosis for patients with primary breast cancer involving multiple axillary lymph nodes is poor. Only about 30% of patients remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy, and radiation therapy. In nonrandomized studies, the use of high-dose chemotherapy as consolidation therapy after standard-dose induction chemotherapy has resulted in an apparent improvement in disease-free survival rates to over 70%. These results have prompted the National Cancer Institute to sponsor large-scale, multicenter, randomized comparative trials of this strategy. This Intergroup Study (Cancer and Leukemia Group B 9082, Southwest Oncology Group 9114, and National Cancer Institute of Canada MA13) compares two treatment strategies in women with primary breast cancer involving 10 or more axillary lymph nodes. Arms A and B are identical in the use of four cycles of conventional therapy with cyclophosphamide and doxorubicin and fluorouracil, radiation therapy, and tamoxifen. The only difference between the two arms is the dose intensity of the cyclophosphamide, cisplatin, and carmustine given following conventional adjuvant treatment. Arm A dictates bone marrow, peripheral blood stem cell, and hematopoietic growth factor support and frequently requires a prolonged hospital stay with high resource utilization. Arm B, with its less dose-intensive therapy, requires considerably less support to apply the treatment. Because of the high cost of this therapy and the requirement for technology-intensive support, there has been considerable interest in economic outcome assessments.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Neoplasias da Mama/terapia , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Metástase Linfática , Estadiamento de Neoplasias
10.
Semin Oncol ; 14(4): 407-15, 1987 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3321445

RESUMO

Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients.


Assuntos
Transplante de Medula Óssea , Leucemia/terapia , Doença Aguda , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Transplante Autólogo/efeitos adversos , Transplante Homólogo/efeitos adversos
11.
Am J Med ; 83(6): 1163-6, 1987 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3332572

RESUMO

Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.


Assuntos
Transplante de Medula Óssea , Tolerância Imunológica , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia/complicações , Micoses/complicações , Infecções Oportunistas/complicações , Doença Aguda , Adolescente , Adulto , Anfotericina B/uso terapêutico , Humanos , Leucemia/terapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Fungos Mitospóricos , Micoses/prevenção & controle , Infecções Oportunistas/prevenção & controle , Indução de Remissão
12.
Am J Med ; 77(4): 645-51, 1984 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6385692

RESUMO

From November 1982 to September 1983, three cases of invasive infection due to Fusarium species were documented in bone marrow transplant recipients. Fusarium was cultured from discrete skin nodules (one patient), maxillary sinus (one patient), or from the blood and surgically excised nasal septum (one patient). All three isolates were resistant to 5-fluorocytosine, whereas only one isolate was resistant to amphotericin B. Although all three patients died, two of the patients had clearing of their Fusarium infection. From this experience and from a review of the literature, it is concluded that despite the dismal prognosis for immunocompromised patients with Fusarium, beneficial therapies would include systemic amphotericin B, local surgical resection, and possibly leukocyte transfusions.


Assuntos
Transplante de Medula Óssea , Fusarium/isolamento & purificação , Micoses/microbiologia , Adolescente , Adulto , Antibacterianos/efeitos adversos , Antifúngicos/uso terapêutico , Antineoplásicos/efeitos adversos , Resistência Microbiana a Medicamentos , Exsudatos e Transudatos/microbiologia , Feminino , Fusarium/efeitos dos fármacos , Fusarium/imunologia , Humanos , Tolerância Imunológica , Imunossupressores/efeitos adversos , Leucemia/complicações , Leucemia/terapia , Contagem de Leucócitos , Masculino , Micoses/prevenção & controle , Micoses/terapia , Complicações Pós-Operatórias/microbiologia , Prognóstico
13.
Am J Med ; 83(3): 464-70, 1987 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3661583

RESUMO

To identify adults with acute nonlymphocytic leukemia at risk for the development of central nervous system involvement, we performed periodic cerebrospinal fluid examinations on patients in remission. Among 58 consecutive patients monitored during first remission, central nervous system leukemia developed in nine (16 percent). Four patients, including one who was symptomatic, had central nervous system leukemia detected simultaneously with marrow relapse. Five additional patients were asymptomatic and continue to have bone marrow remission. Following central nervous system and systemic treatment, two of these five patients have never had relapse, and three had relapse in the bone marrow five, 10, and 21 months later. Factors at diagnosis associated with the subsequent development of central nervous system leukemia were elevated leukocyte count, serum lysozyme and lactate dehydrogenase, extramedullary infiltration including splenomegaly, and monocytic (FAB M4 or M5a) morphology. In six of 17 patients (35 percent) with monocytic morphology, central nervous system leukemia developed compared with only three of 41 patients (7 percent) with other subtypes (p = 0.02). Discriminant analysis identified leukocyte count, splenomegaly, and M4 or M5a morphology as the most important risk factors and led to a mathematical formula that correctly identified 90 percent of the patients. Although the risk of central nervous system leukemia in adults with acute nonlymphocytic leukemia is too low to justify routine prophylaxis, those patients recognized to be at a greater risk should receive prophylaxis or be monitored closely with periodic lumbar punctures.


Assuntos
Leucemia/líquido cefalorraquidiano , Neoplasias Meníngeas/líquido cefalorraquidiano , Doença Aguda , Adulto , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Leucemia/diagnóstico , Contagem de Leucócitos , Masculino , Neoplasias Meníngeas/diagnóstico , Muramidase/sangue , Estudos Prospectivos , Fatores de Risco , Esplenomegalia/etiologia
14.
Am J Med ; 85(6): 829-34, 1988 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3057901

RESUMO

PURPOSE: Patients with non-Hodgkin's lymphoma who fail to achieve a complete remission or who relapse are rarely cured with conventional therapies. For this group of patients, intensive therapy and bone marrow rescue may be curative. Our goal was to assess the effects of autologous transplantation in patients with B-cell lymphomas and a poor prognosis. To avoid occult or overt contamination with lymphoma, monoclonal antibodies BA-1, BA-2, and BA-3 were used for ex vivo marrow treatment. PATIENTS AND METHODS: Seventeen patients underwent intensive therapy and autologous bone marrow transplant using the aforementioned marrow. Ten of the 17 patients (Group I) had disease that was in complete or partial remission. The other seven patients either had disease that was not responsive to treatment or had bone marrow transplant as their initial therapy at relapse. RESULTS: The ex vivo treatment did not adversely affect engraftment. For those patients who could be evaluated, the median time to white cell engraftment was 24 days; the median durations of red cell and platelet support were 24 and 29 days, respectively. Eleven of the 17 patients had complete remissions at the evaluation 28 days after transplant. Three patients subsequently experienced a relapse, three died while their disease was in complete remission, and five are alive and disease-free 405 to 1,674 days after transplant. Group I patients had an estimated 40 percent disease-free survival rate at three years compared with 0 percent for Group II patients (p less than 0.01). CONCLUSION: Our data support autologous bone marrow transplantation as an important treatment modality for the non-Hodgkin's lymphomas. With the current preparative regimens available, however, its use should be limited to patients with disease that is still responding to conventional therapies.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Transplante de Medula Óssea , Proteínas do Sistema Complemento/administração & dosagem , Linfoma não Hodgkin/cirurgia , Transplante Autólogo/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Indução de Remissão
15.
Leuk Res ; 9(8): 993-9, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-4046634

RESUMO

Glucocorticoid receptor (GR) levels have not been extensively studied in untreated patients with chronic lymphocytic leukemia (CLL). We have measured tumor GR levels using a whole cell assay in 18 untreated patients with CLL and correlated these levels with various in-vitro and in-vivo data. In 12 of these patients, tumor cells from more than one tissue were simultaneously studied. Measurable GR levels were found in all 36 specimens studied with median total GR levels in blood, bone marrow, and lymph nodes being 3018 (n = 17), 3524 (n = 12) and 3102 (n = 7) sites/cell respectively. GR levels did not correlate with in-vitro sensitivity, as measured by inhibition by dexamethasone of radiolabelled leucine, uridine, and thymidine uptake, nor with the clinical or laboratory features examined. Nine patients were treated with dexamethasone as a single agent; blood GR levels were not predictive of antitumor response. We conclude that in patients with CLL, malignant cells from all involved tissues have measurable numbers of GRs, but these are not correlated with in-vitro sensitivity to glucocorticoid. Blood GR levels do not correlate with antitumor response; further studies are required to see if bone marrow or lymph node receptor levels correlate with antitumor response to steroids.


Assuntos
Leucemia Linfoide/metabolismo , Receptores de Glucocorticoides/análise , Dexametasona/uso terapêutico , Feminino , Humanos , Leucemia Linfoide/tratamento farmacológico , Linfonodos/análise , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico
16.
Chest ; 111(1): 135-41, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8996007

RESUMO

STUDY OBJECTIVE: To determine the impact of fiberoptic bronchoscopy (FOB), including quantitative bacterial cultures obtained by BAL and protected specimen brushing on therapeutic decisions and outcome in bone marrow transplant (BMT) patients. DESIGN: Retrospective review of all BMT patients undergoing FOB during a 4-year period. SETTING: A tertiary care university hospital. RESULTS: Three hundred five patients underwent BMT; 71 (23%) had FOB to assess pulmonary infiltrates. Allogeneic BMT recipients underwent FOB 3.37 times more often than autologous recipients (p < 0.001). Pathogens were identified in 31 (46%) patients undergoing FOB; bacteria were most commonly isolated although 86% of patients had received broad-spectrum empiric antibiotics. Therapy was changed in 20 (65%) patients when a microorganism was identified and in 9 (22%) with nondiagnostic results (p = 0.0026), but isolation of a presumed pathogen had no apparent effect on survival. There were 19 (27%) FOB complications, including bleeding in 8 (11%) patients and death in 2 (3%). Major complications were associated with prolonged prothrombin time (p = 0.006) and were more common (36% vs 14%; p < 0.05) in patients who had protected specimen brushing vs BAL alone. Mortality at 40 months in BMT patients not requiring FOB was 33% compared with 61% mortality in those undergoing FOB (p < 0.001); mortality was 96% in patients with respiratory failure requiring mechanical ventilation. CONCLUSION: FOB is diagnostically useful in the evaluation of some BMT patients with pulmonary complications and often influences therapy, although no impact on survival was clearly demonstrated. FOB should be performed only after benefits of the procedure are weighed carefully against its increased risk in this select population.


Assuntos
Transplante de Medula Óssea , Broncoscopia , Pneumopatias/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Adulto , Feminino , Tecnologia de Fibra Óptica , Humanos , Leucemia/mortalidade , Leucemia/cirurgia , Linfoma/mortalidade , Linfoma/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
17.
Bone Marrow Transplant ; 7(6): 435-7, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1873590

RESUMO

The incidence of varicella-zoster-virus infection/reactivation in adult patients with Hodgkin's disease undergoing autologous bone marrow transplantation (BMT) at the University of Minnesota Hospital and Clinic was determined. Seven of 28 evaluable patients (25%) developed varicella-zoster infections in the first 150 days post-transplant. Two additional patients developed zoster after day 150 for a total incidence of 32%. We evaluated analysed risk factors to determine if there were any characteristics that could identify patients at risk for zoster early (less than 150 days) in their post-transplant course. Sex, age, prior radiation, and lack of immunity as determined by viral antibody titers were not associated with an increased incidence. Ten of the 28 patients had a history of zoster at some time after the diagnosis of Hodgkin's disease. Six of these 10 patients (60%) again developed zoster post-transplant. This compared to only one episode of varicella-zoster post-transplant among the 18 patients without a history of zoster following the diagnosis of Hodgkin's disease (p less than 0.01, Fisher's exact). We conclude that a prior history of zoster any time after diagnosis of Hodgkin's disease is strongly associated with developing zoster in the first 150 days after autologous BMT.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Herpes Zoster/etiologia , Doença de Hodgkin/cirurgia , Adolescente , Adulto , Fatores Etários , Anticorpos Antivirais/análise , Testes de Fixação de Complemento , Ensaio de Imunoadsorção Enzimática , Feminino , Herpes Zoster/epidemiologia , Herpes Zoster/patologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais
18.
Bone Marrow Transplant ; 15(6): 983-7, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7581102

RESUMO

The objective of this study was to report the occurrence of reactivation ocular toxoplasmosis in bone marrow transplant (BMT) recipients and to propose guidelines for identification and chemoprophylaxis of high-risk patients. The study design was a series of cases from the tertiary care university hospital which has an active BMT program. The patients were two recipients of autologous BMTs with past histories of toxoplasma retinochoroiditis who developed symptomatic reactivation of ocular toxoplasmosis as documented by formal opthalmologic examination in the early post-transplant period. Opthalmoscopic examinations in the two patients with non-Hodgkin's lymphoma who received autologous transplants and then developed decreased visual acuity in the first week after transplant revealed recurrent retinochoroiditis adjacent to old toxoplasma lesions. Pre-transplant eye examinations in both patients had demonstrated only inactive chorioretinal scars. Therapy with sulfadiazine, pyrimethamine and prednisone ultimately led to resolution of retinitis in both patients. BMT recipients who are seropositive for antibody to T. gondii and have findings consistent with previous toxoplasma retinochoroiditis on pre-transplant ophthalmologic examination appear to be at risk for reactivation of ocular toxoplasmosis in the early post-transplant period and may warrant preventive chemoprophylaxis for toxoplasmosis.


Assuntos
Antiprotozoários/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Coriorretinite/parasitologia , Hospedeiro Imunocomprometido , Linfoma Difuso de Grandes Células B/terapia , Linfoma não Hodgkin/terapia , Infecções Oportunistas/etiologia , Toxoplasma/fisiologia , Toxoplasmose Ocular/etiologia , Animais , Anticorpos Antiprotozoários/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Coriorretinite/tratamento farmacológico , Coriorretinite/etiologia , Coriorretinite/prevenção & controle , Terapia Combinada , Evolução Fatal , Humanos , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/prevenção & controle , Prednisona/uso terapêutico , Pirimetamina/uso terapêutico , Sulfadiazina/uso terapêutico , Toxoplasma/imunologia , Toxoplasmose Ocular/tratamento farmacológico , Toxoplasmose Ocular/prevenção & controle
19.
Bone Marrow Transplant ; 31(3): 219-22, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12621485

RESUMO

A 39-year-old male underwent a nonmyeloablative stem cell transplant (NMAPBPCT) from his HLA-matched sister for recurrent anaplastic large cell lymphoma in CR-2, receiving fludarabine, cyclophosphamide, and rabbit antithymocyte globulin for the preparative therapy. The patient was readmitted on day+33 for persistent culture-negative fevers. He rapidly developed marked elevations of alkaline phosphatase and bilirubin. Liver biopsy showed a periportal infiltrate of large immunoblastic appearing cells. The tumor cells did not stain for CD3/CD20/CD30 and alk protein, but did stain for CD79a/LCA and CD43. In situ hybridization for Epstein-Barr virus (EBV) RNA (EBER 1) was strongly positive in the periportal infiltrating lymphocytes. Fluorescence in situ hybridization (FISH) studies revealed female (XX) cells in the tumor cells and male (XY) in the surrounding hepatic parenchymal cells. The patient developed severe lactic acidosis, oliguric renal failure and expired on day+44. Both donor and patient had positive IgG serologies for EBV VCA and EBNA pretransplant. The donor also had a positive IgM titer for EBV VCA in the pretransplant specimen. The LPD may have been related to the intense immunosuppression of the preparative therapy and the presence of recent EBV infection in the donor.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Linfoma de Células T/terapia , Transtornos Linfoproliferativos/virologia , Transplante de Células-Tronco/efeitos adversos , Adulto , Antígenos CD/análise , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Evolução Fatal , Humanos , Fígado/patologia , Linfonodos/imunologia , Linfonodos/patologia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/imunologia , Linfoma de Células T/patologia , Masculino , Prednisona/administração & dosagem , Vincristina/administração & dosagem
20.
Bone Marrow Transplant ; 18(3): 579-84, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8879621

RESUMO

The purpose of this study was to compare pre- and posttreatment quality of life (QOL) in breast cancer patients undergoing high-dose chemotherapy with autologous bone marrow transplantation (ABMT). Fifty-two female breast cancer patients were assessed on overall QOL, mood status, and social support before transplantation. After ABMT, 24 patients were assessed on the same measures as well as a measure of depressive symptoms and specific concerns identified in a structured interview. Mean pre- and post-transplant scores on the quality of life measure, mood scores and social support were not significantly different. Eight patients (33%) reported depressive symptoms post-transplantation. In the structured interview, a percentage of patients reported concerns in the following areas: job or work situation (25%); finances (42%); general physical health (50%); general frame of mind (25%); appearance (33%); health or life insurance (37%); personal or intimate physical relations (33%); planning for the future (38%). QOL and mood following ABMT improved slightly and compares favorably with breast cancer patients treated with conventional treatment. However, approximately 30% of patients had problems with sexuality, fatigue and depressive symptoms and may need follow-up psychosocial care in these areas. ABMT may pose no more threat to quality of life than conventional chemotherapy.


Assuntos
Transplante de Medula Óssea , Neoplasias da Mama/psicologia , Qualidade de Vida , Adulto , Neoplasias da Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Apoio Social , Transplante Autólogo
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