RESUMO
The immunologic consequences of prolonged infusions of rIL-2 in doses that produce physiologic serum concentrations of this cytokine were investigated. rIL-2 in doses of 0.5-6.0 x 10(6) U/m2 per d (3.3-40 micrograms/m2 per d) was administered by continuous intravenous infusion for 90 consecutive days to patients with advanced cancer. IL-2 concentrations (25 +/- 25 and 77 +/- 64 pM, respectively) that selectively saturate high-affinity IL-2 receptors (IL-2R) were achieved in the serum of patients receiving rIL-2 infusions of 10 micrograms/m2 per d and 30 micrograms/m2 per d. A gradual, progressive expansion of natural killer (NK) cells was seen in the peripheral blood of these patients with no evidence of a plateau effect during the 3 mo of therapy. A preferential expansion of CD56bright NK cells was consistently evident. NK cytotoxicity against tumor targets was only slightly enhanced at these dose levels. However, brief incubation of these expanded NK cells with IL-2 in vitro induced potent lysis of NK-sensitive, NK-resistant, and antibody-coated targets. Infusions of rIL-2 at 40 micrograms/m2 per d produced serum IL-2 levels (345 +/- 381 pM) sufficient to engage intermediate affinity IL-2R p75, which is constitutively expressed by human NK cells. This did not result in greater NK cell expansion compared to the lower dose levels, but did produce in vivo activation of NK cytotoxicity, as evidenced by lysis of NK-resistant targets. There was no consistent change in the numbers of CD56- CD3+ T cells, CD56+ CD3+ MHC-unrestricted T cells, or B cells during infusions of rIL-2 at any of the dosages used. This study demonstrates that prolonged infusions of rIL-2 in doses that saturate only high affinity IL-2R can selectively expand human NK cells for an extended period of time with only minimal toxicity. Further activation of NK cytolytic activity can also be achieved in vivo, but it requires concentrations of IL-2 that bind intermediate affinity IL-2R p75. Clinical trials are underway attempting to exploit the differing effects of various concentrations of IL-2 on human NK cells in vivo.
Assuntos
Interleucina-2/uso terapêutico , Células Matadoras Naturais/efeitos dos fármacos , Neoplasias/imunologia , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Antígeno CD56 , Humanos , Infusões Intravenosas , Interleucina-2/administração & dosagem , Células Matadoras Naturais/imunologia , Neoplasias/sangue , Neoplasias/terapia , Receptores de Interleucina-2/análise , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Fatores de TempoRESUMO
Several recently published studies have suggested that patients who undergo ABO mismatched hematopoietic stem cell transplantation may be at increased risk for relapse, graft-versus-host disease, transplant-related mortality, and/or all-cause mortality. To investigate this issue further, we analyzed potential associations between the donor-recipient ABO mismatch pattern and the above outcome measures among 240 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation at our institution. Our analyses uncovered no significant associations between donor-recipient ABO mismatch pattern and overall survival, event-free survival, transplant-related mortality, incidence of acute graft-versus-host disease (GVHD), or incidence of chronic GVHD. Our data do not support recent assertions that donor-recipient ABO mismatching is a major risk factor for patients undergoing allogeneic transplant, nor do they support recent assertions that ABO matching should be an important consideration in selecting allogeneic hematopoietic stem cell donors.
Assuntos
Sistema ABO de Grupos Sanguíneos , Seleção do Doador , Transplante de Células-Tronco Hematopoéticas/mortalidade , Neoplasias/mortalidade , Doadores de Tecidos , Tipagem e Reações Cruzadas Sanguíneas/métodos , Intervalo Livre de Doença , Seleção do Doador/métodos , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Neoplasias/terapia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Transplante HomólogoRESUMO
An alpha 2-macroglobulin with trypsin-like activity has been purified from pleural fluids of patients suffering from chronic pancreatitis. The isolation procedure includes ammonium sulphate precipitation, gel-filtration on Sephadex G-200 and DEAE-cellulose chromatography. It gives 46-fold purification of alpha 2-macroglobulin with a 13% recovery. Based on titration experiments with pancreatic inhibitor, the protein from three different patients contained 0.28, 0.46 and 0.80 mol of trypsin-like protease per mol of alpha 2-macroglobulin.
Assuntos
Complexos Multienzimáticos/isolamento & purificação , Derrame Pleural/enzimologia , Tripsina/metabolismo , alfa-Macroglobulinas/isolamento & purificação , Cromatografia em Gel , Doença Crônica , Humanos , Pancreatite/enzimologia , alfa-Macroglobulinas/metabolismoRESUMO
PURPOSE: To determine the value of pretransplant studies in predicting day 100 nonrelapse toxic mortality following high-dose therapy. PATIENTS AND METHODS: A retrospective review of 383 consecutive hematopoietic stem-cell transplants was performed with attention to toxic mortality and pretransplant factors. Univariate log-rank analysis was used to yield the most significant cut-off values for individual factors. Multivariate analysis using Cox proportional hazards regression determined factors independently predictive of early toxic death. RESULTS: Nonrelapse toxic mortality before day 100 occurred in 23 of 383 (6.0%) transplant recipients. Factors associated with an increased risk of toxic death by univariate analysis included forced expiratory volume in 1 second (FEV1) less than 78% of predicted (P = .0002), allogeneic versus autologous transplant (P = .0003), diffusion capacity of carbon monoxide less than 52% of predicted (P = .002), serum creatinine concentration greater than 1.1 mg/dL (P = .003), Eastern Cooperative Oncology Group performance status greater than 0 (P = .006), preparative regimen containing total-body irradiation versus chemotherapy alone (P = .006), marrow versus blood stem cell (P = .01), serum ALT greater than 50 IU/L (P = .02), diagnosis of hematologic disorder versus solid tumor (P = .06), serum bilirubin level greater than 1.1 mg/dL (P = .08), left ventricular ejection fraction (P = .09), and growth factor use (P = .09). In the multivariate model, transplant type (relative risk, 4.2), FEV1 (relative risk, 4.5), performance status (relative risk, 3.7), serum creatinine (relative risk, 3.8), and serum bilirubin (relative risk, 3.7) were found to be independent predictors of early toxic mortality. CONCLUSION: The pretransplant evaluation is a useful tool to identify patients at risk for early toxic mortality following high-dose therapy.
Assuntos
Transplante de Medula Óssea/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Exame Físico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Fatores de Risco , Análise de Sobrevida , Fatores de TempoRESUMO
PURPOSE: It is well-established that the infusion of hematopoietic growth factors (HGF) accelerates neutrophil recovery in patients undergoing high-dose therapy followed by autologous bone marrow infusion. In addition, there is evidence that the infusion of autologous peripheral-blood stem cells (PBSC) accelerates engraftment in comparison to patients who receive bone marrow alone. However, few data are available regarding the ability of HGF to accelerate engraftment further in patients who receive PBSC following high-dose therapy. PATIENTS AND METHODS: Forty-one patients undergoing high-dose therapy followed by infusion of autologous PBSC with or without bone marrow were randomized to receive granulocyte colony-stimulating factor (G-CSF) 5 micrograms/kg/d beginning on day + 1 following transplant or standard posttransplant supportive care without HGF. RESULTS: The median time to a neutrophil count > or = 500/microL was 10.5 days in the G-CSF group versus 16 days in the control group (P = .0001). G-CSF was associated with statistically significant reductions in the time to neutrophil engraftment among patients who received PBSC alone (11 v 17 days, P = .0003) and in patients who received PBSC in conjunction with bone marrow (10 v 14 days, P = .02). The median duration of posttransplant hospitalization (18 v 24 days, P = .002) and the median number of days on nonprophylactic antibiotics (11 v 15, P = .03) were also significantly reduced. CONCLUSION: Administration of G-CSF in the posttransplant period accelerates the rate of neutrophil engraftment, shortens the duration of hospitalization, and reduces the number of days on nonprophylactic antibiotics in patients who receive autologous PBSC with or without autologous bone marrow following high-dose therapy.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Neutropenia/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
In previous clinical trials, recombinant interleukin-2 (rIL-2) has been infused at high doses over short periods of time to generate lymphokine-activated killer (LAK) cells in vivo. These trials have been limited by severe toxicities, and the immunologic effects of rIL-2 have been transient. The present study was designed to assess the toxicity and immunologic effects of prolonged administration of low doses of rIL-2. In this phase I study, patients with advanced cancer were scheduled to receive intravenous (IV) infusion of rIL-2 without interruption for 3 months in an outpatient setting. Twenty-one patients received rIL-2 at doses ranging from 0.5 x 10(5) to 6.0 x 10(5) U/m2/d. Treatment was extremely well tolerated, and no patient experienced grade 3 or grade 4 toxicity. The lowest dose level (0.5 x 10(5) U/m2/d) did not have demonstrable immunologic activity. At doses of 1.5 x 10(5) and 4.5 x 10(5) U/m2/d, rIL-2 infusion resulted in the specific expansion of natural-killer (NK) cells (sixfold and ninefold increases, respectively, at these two dose levels) without any changes in B cells, T cells, neutrophils, or monocytes. Grade 2 toxicity was observed at the dose of 6.0 x 10(5) U/m2/d, as three patients required interruption of therapy and two patients who completed therapy developed transient hypothyroidism. In patients with increased NK cells, enhancement of non-major histocompatibility complex (MHC)-restricted cytotoxicity and increased generation of LAK cells in vitro were also demonstrated. Therapy with low-dose rIL-2 can be given safely in an uninterrupted fashion for prolonged periods of time in an outpatient setting. This results in selective expansion of NK cells in vivo with minimal toxicity. Further investigation of this schedule for immunomodulation in vivo should be pursued in phase II studies of both malignant and immunodeficient disease states.
Assuntos
Interleucina-2/administração & dosagem , Interleucina-2/efeitos adversos , Neoplasias/tratamento farmacológico , Adulto , Idoso , Assistência Ambulatorial , Cateterismo Venoso Central , Cateteres de Demora , Feminino , Humanos , Bombas de Infusão , Linfocitose/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Fatores de TempoRESUMO
We describe 3 cases of immune-mediated cytopenia occurring after bone marrow transplantation (BMT). In 1 case, only the platelet line was affected, whereas in the other 2 cases more than 1 cell lineage was involved simultaneously. Two of the cases presented with falling peripheral blood counts following apparently normal early engraftment, while in 1 of the cases the affected lineage failed to appear in the peripheral blood despite normal engraftment of the other lineages. In all 3 cases the cytopenia improved following the initiation of treatment with systemic corticosteroids. Immune-mediated cytopenia following bone marrow transplantation may occur via alloimmune or autoimmune mechanisms. Alloimmune cytopenias have arisen in the context of major or minor mismatches in the ABO system, but cases related to mismatches in the Rh system and other erythroid and non-erythroid alloantigen systems may also occur. Alloimmune cytopenias have been reported primarily in the setting of allogeneic BMT, whereas autoimmune cytopenias have been reported following both allogeneic and autologous BMT. Immune-mediated cytopenia may present as early as the day of transplant, or as late as many months afterward. The possibility of immune-mediated cytopenia should always be considered when unexpected peripheral blood cytopenia is present, or when unexpected hemolysis develops, following bone marrow transplantation. The diagnosis is supported by a normal appearance of the affected lineage or lineages in the bone marrow, the absence of other apparent causes for the cytopenia, and the presence of the relevant auto- or allo-antibodies in the serum. However, any of these features may be absent in individual cases. The importance of these syndromes lies in the fact that they may be life-threatening, yet they often respond well to steroids or other standard immunosuppressive measures. It is important to be aware that effective prophylactic measures are available for patients receiving ABO- or Rh-incompatible marrow.
Assuntos
Anemia Hemolítica/imunologia , Transplante de Medula Óssea/efeitos adversos , Leucopenia/imunologia , Trombocitopenia/imunologia , Adulto , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/terapia , Southern Blotting , Transplante de Medula Óssea/imunologia , Mapeamento Cromossômico , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Leucopenia/diagnóstico , Leucopenia/terapia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Esplenectomia , Trombocitopenia/diagnóstico , Trombocitopenia/terapiaRESUMO
Normal hematopoiesis depends on successful interaction between the immune system and the hematopoietic system. The special circumstances of bone marrow transplantation (BMT) give rise to a number of well-recognized adverse interactions between these two systems, which are often manifested as peripheral blood cytopenias involving one or more cell lines. These so-called immunohematologic complications of BMT may develop following allogeneic, autologous, or syngeneic transplantation, and may occur as early as the day of transplantation or as late as several years afterward. Both autoimmune and alloimmune mechanisms have been implicated. The possibility of an immunohematologic complication should be considered any time an unexpected cytopenia develops in one or more cell lines in the post-transplant period. In addition, immunohematologic complications should be anticipated, and appropriate prophylaxis administered, when there is a major or minor mismatch between the donor and the recipient in the ABO and/or Rh blood group systems. Approaches to the prophylaxis, diagnosis, and treatment of these syndromes are reviewed herein.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Doenças Hematológicas/etiologia , Doenças do Sistema Imunitário/etiologia , Transplante de Medula Óssea/imunologia , Transplante de Medula Óssea/fisiologia , Sistema Hematopoético/fisiologia , Humanos , Sistema Imunitário/fisiologiaRESUMO
We report two cases of severe leg ulcerations in patients being treated with thalidomide for graft-versus-host disease following bone marrow transplantation. Local wound care and debridement were attempted, but one patient required skin grafting to ensure healing. We propose that this complication may be due to the antiangiogenic properties of thalidomide and urge careful attention to skin breakdown in patients being treated with this compound.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Imunossupressores/efeitos adversos , Leucemia Linfocítica Crônica de Células B/terapia , Úlcera Cutânea/etiologia , Talidomida/efeitos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Talidomida/uso terapêutico , Transplante HomólogoRESUMO
The combination of busulfan and CY ('BU-CY') has been widely employed as a conditioning regimen for patients undergoing BMT for hematologic malignancies. However, little information is available regarding the utility of BU-CY in treating patients with advanced breast cancer. Fifteen patients with heavily pretreated Stage IIIB or Stage IV chemosensitive breast cancer were treated with busulfan (16 mg/kg) and CY (6000 mg/m2) followed by rescue with autologous BM or autologous peripheral blood stem cells. Toxicity and engraftment parameters were similar to those observed in patients receiving BU-CY for other indications. The overall response rate was 87%, with 53% of patients achieving CR. The median progression-free survival was 164 days, and the median overall survival was 292 days. We conclude that BU-CY is able to induce remissions in a high percentage of patients with heavily pretreated advanced breast cancer. However, remissions are brief, and alternative strategies for patient selection and/or management will be necessary to improve on these results.
Assuntos
Adenocarcinoma/cirurgia , Transfusão de Componentes Sanguíneos , Purging da Medula Óssea , Transplante de Medula Óssea , Neoplasias da Mama/cirurgia , Bussulfano , Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transfusão de Sangue Autóloga , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Projetos Piloto , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Análise de Sobrevida , Transplante Autólogo , Resultado do TratamentoRESUMO
This study was conducted to determine if the accelerated telomere attrition that occurs as a consequence of allogeneic stem cell transplantation leads to measurable functional defects. Telomere lengths in mononuclear leukocytes obtained from 15 long-term allogeneic stem cell transplant recipients and their respective donors were determined by Southern hybridization and densitometric analysis. Functional assays evaluated the ability of these cells to proliferate in response to a mitogenic stimulus and to differentiate under appropriate cytokine stimulation. Lymphocyte proliferation in response to phytohemagglutinin was determined by measurement of (3)[H]thymidine uptake. The ability of circulating myeloid cells to differentiate was determined after incubation of peripheral blood mononuclear cells with IL-3 and GM-CSF. A total of 13 patients demonstrated telomeric loss, ranging from 0.1 to 3.7 kbp. Strikingly, lymphocytes from 14 of the 15 patients demonstrated a significant decrease in proliferation when compared to their respective donors (68%+/-22, P=0.001). All patients demonstrated at least a 50% decrease in the number of myeloid colony-forming units when compared to their respective donors (P<0.0001). A decreased ability of hematopoietic cells to proliferate and differentiate is phenotypically consistent with an aged immune system. This may correlate with diminished clinically relevant immune responses to infection or vaccination, as seen in the elderly.
Assuntos
Transplante de Medula Óssea/normas , Sistema Imunitário/fisiopatologia , Transplante de Células-Tronco de Sangue Periférico/normas , Telômero/imunologia , Adulto , Idoso , Diferenciação Celular/efeitos dos fármacos , Senescência Celular , Citocinas/farmacologia , Feminino , Hematopoese , Humanos , Sistema Imunitário/citologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/fisiologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Células Mieloides/citologia , Células Progenitoras Mieloides , Mielopoese , Fito-Hemaglutininas/farmacologia , Sobreviventes , Telômero/ultraestrutura , Transplante HomólogoRESUMO
Previous reports have suggested that antibodies reactive with neutrophils (ARN) are frequently detectable in patients undergoing bone marrow or blood stem cell transplantation (BMT), and that such antibodies result in steroid-responsive delayed neutrophil engraftment or steroid-responsive post-engraftment neutropenia in some patients. However, the true incidence and significance of ARN in the BMT setting remain poorly established because most of the published data are in the form of retrospective case reports. Therefore, we prospectively studied the incidence of ARN, the rate of neutrophil engraftment, and the incidence of post-engraftment neutropenia in a cohort of 40 BMT candidates. Sixteen of the 36 evaluable patients (44%) had detectable ARN following transplant vs none of 25 concurrently studied healthy controls (P < 0.0001). Patients with detectable ARN in the post-transplant period recovered to an absolute neutrophil count (ANC) of 500 x 10(9)/l a median of 3.5 days later than patients without detectable ARN; multivariate analysis controlling for the potential effects of diagnosis, conditioning regimen, amount of prior therapy, and other factors revealed that only the administration of hematopoietic growth factors (P = 0.008) and the presence of ARN in the post-transplant period (P = 0.016) were independently predictive of the rate of neutrophil engraftment following BMT. Four of the 16 patients with detectable ARN (25%) satisfied previously published criteria for post-engraftment neutropenia, ie a fall in the ANC to less than 500 x 10(9)/l for at least 2 consecutive days, following initial engraftment to an ANC of at least 1000 x 10(9)/l for at least 2 consecutive days. In contrast, none of the 20 patients without detectable post-transplant ARN developed post-engraftment neutropenia. Multivariate analysis revealed that only the presence of ARN in the post-transplant period (P = 0.022) was independently predictive of post-engraftment neutropenia. All four patients with ARN-associated post-engraftment neutropenia responded to steroid-based therapy. These prospectively gathered data support previously published primarily case report data suggesting that ARN occur frequently following BMT and are associated with an increased incidence of delayed neutrophil engraftment and post-engraftment neutropenia. As is the case in the non-transplant setting, ARN-associated neutropenia occurring following BMT may respond to steroid-based therapy.
Assuntos
Anticorpos/sangue , Transplante de Medula Óssea/efeitos adversos , Neutropenia/etiologia , Neutrófilos/imunologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
An 18-year-old white male developed severe hepatic veno-occlusive disease (VOD) during an autologous bone marrow transplant for primary refractory nodular sclerosing Hodgkin's disease. As a result of VOD-induced hepatic dysfunction, coagulation studies revealed depression of vitamin K dependent procoagulant factor VII. Intravenous recombinant tissue plasminogen activator 20 mg over h on 4 consecutive days and continuous heparin infusion (1000 unit bolus followed by 150 units/kg/day) resulted in rapid reversal of the VOD syndrome. During treatment, procoagulant factors II, VII, IX and X levels increased indicating the return of hepatic synthesizing capacity. Factor V levels, which were elevated pre-therapy, also rose dramatically. Plasma antigen levels of protein C, a natural anticoagulant, remained severely depressed. No clinical evidence of bleeding and only minimal systemic fibrinolysis was noted. Despite concerns regarding the use of lytic therapy in a thrombocytopenic post-BMT patient, serial measurements of coagulation parameters during severe VOD suggested that low dose rt-PA improved portions of the systemic hemostatic profile.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Transplante de Medula Óssea/efeitos adversos , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Adolescente , Humanos , Masculino , Proteínas Recombinantes/uso terapêuticoRESUMO
Seventy women with high-risk stage II (n = 10), IIIA (n = 12), IIIB (n = 11), or IV (n = 37) breast cancer received cyclophosphamide 6000 mg/m2, etoposide 2400 mg/m2, and carboplatin 1200 mg/m2 followed by infusion of autologous hematopoietic stem cells (AHSC). Women with high-risk stage II disease had eight or more involved axillary lymph nodes (n = 9) or axillary and breast relapse following lumpectomy, chemotherapy, and radiation therapy (n = 1). Women with measurable stage III or stage IV disease were required to demonstrate complete or partial response to conventional-dose chemotherapy prior to transplant. The overall (complete plus partial) response rate for the 31 patients not in complete remission at the time of transplant was 55%. With a median follow-up of 545 days, the 2-year actuarial progression-free survival rates for patients with stage II, IIIA, IIIB and IV are 86, 75, 42 and 13%, respectively. Factors independently predictive of longer progression-free survival by multivariate analysis included lower stage disease, status of disease at transplant (in CR vs not in CR), and positive estrogen receptor status. Factors predictive of more rapid neutrophil engraftment by multivariate analysis included post-transplant administration of hematopoietic growth factors, greater number of infused CFU-GM, mobilization with G-CSF or cyclophosphamide/G-CSF (vs mobilization with GM-CSF or no mobilization), and lower stage disease. Only one patient (1.4%) died prior to day 100 from any cause. High-dose cyclophosphamide, etoposide, and carboplatin followed by infusion of AHSC constitutes an active and well-tolerated regimen in the treatment of women with high-risk non-metastatic or metastatic breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transfusão de Sangue , Neoplasias da Mama/mortalidade , Carboplatina/administração & dosagem , Ciclofosfamida/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Taxa de Sobrevida , Transplante AutólogoRESUMO
We report a case of unexplained graft failure in a 33-year-old man who received an allogeneic bone marrow graft that contained a donor-recipient mismatch involving the highly immunogenic NA1 neutrophil-specific alloantigen system. Laboratory and clinical data suggest that an alloimmune process related to the neutrophil alloantigen mismatch played a role in the development of the graft failure.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Rejeição de Enxerto/imunologia , Isoantígenos , Neutrófilos/imunologia , Adulto , Transplante de Medula Óssea/imunologia , Humanos , Leucemia Mieloide Aguda/cirurgia , Masculino , Neutropenia/etiologia , Neutropenia/imunologia , Fenótipo , Doadores de TecidosRESUMO
We conducted a phase I/II study to determine the efficacy, toxicity and maximum tolerable doses of CY, etoposide and cisplatin (CEP) in the management of patients with relapsed or refractory malignant lymphoma. Thirty patients with relapsed or refractory Hodgkin's disease (n = 10) or non-Hodgkin's lymphoma (n = 20) received CY 6000 mg/m2, etoposide 900-2700 mg/m2 and cisplatin 150 mg/m2 followed by autologous BM or autologous peripheral blood stem cell rescue. The dose of etoposide was escalated after each 3 to 4 patients. The maximum tolerated dose of etoposide, when administered with the indicated doses of CY and cisplatin, was 2400 mg/m2. Three of the 30 patients (10%) died of treatment-related toxicity. Although 14 of the 30 patients had residual bulky and/or chemotherapy-resistant disease at the time of the transplant, 26 patients (87%) responded to this regimen, including 18 patients (60%) who achieved CR and 8 patients (27%) who achieved partial remission. Seven patients (23%) remain alive and free of progression at a median of 21 months post-transplant. Three additional patients relapsed after transplant but are enjoying prolonged disease-free survival at a median of 31 months post-transplant following additional post-transplant therapy. We conclude that high-dose CY, etoposide and cisplatin followed by autologous BM or peripheral blood stem cell rescue is an active and acceptably tolerated regimen in the treatment of relapsed or refractory malignant lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transfusão de Componentes Sanguíneos , Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/cirurgia , Humanos , Fatores Imunológicos/uso terapêutico , Tábuas de Vida , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de SobrevidaRESUMO
A 47-year-old female developed autoimmune hemolytic anemia, autoimmune neutropenia, and autoimmune thrombocytopenia 19 months following allogeneic bone marrow transplantation for chronic myelogenous leukemia. Treatment with high-dose corticosteroids resulted in marked improvement in all three cell lines.
Assuntos
Doenças Autoimunes/etiologia , Transplante de Medula Óssea/efeitos adversos , Reação Hospedeiro-Enxerto , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Pancitopenia/etiologia , Doenças Autoimunes/tratamento farmacológico , Transplante de Medula Óssea/imunologia , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Pessoa de Meia-Idade , Pancitopenia/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/etiologia , Prednisona/uso terapêutico , Transplante Homólogo/efeitos adversos , Transplante Homólogo/imunologiaRESUMO
A patient developed secondary acute myelogenous leukemia with a 20q- marker chromosome abnormality six years following chemotherapy and radiation for Hodgkins disease (HD). Routine cytogenetics on the bone marrow which had been harvested and cryopreserved immediately following completion of initial therapy for HD showed no cytogenetic abnormality. However, a 20q- clonal marker was detected after culturing bone marrow with hematopoietic growth factors (HGF). The marrow was used successfully for an autotransplant. Post-transplant, the 20q- marker was again detected in HGF cultured samples. The patient relapsed at 165 days post-transplant with the 20q- marker and trisomy 21. These data suggest that standard cytogenetic assays may not detect abnormal clones which can cause leukemia post-transplant.
Assuntos
Transplante de Medula Óssea , Medula Óssea/patologia , Deleção Cromossômica , Cromossomos Humanos Par 20/ultraestrutura , Fatores de Crescimento de Células Hematopoéticas/farmacologia , Segunda Neoplasia Primária/patologia , Células-Tronco Neoplásicas/patologia , Doença Aguda , Adulto , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Anemia Refratária com Excesso de Blastos/etiologia , Anemia Refratária com Excesso de Blastos/patologia , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Medula Óssea/efeitos dos fármacos , Células Clonais/patologia , Terapia Combinada , Citarabina/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Mecloretamina/administração & dosagem , Mecloretamina/efeitos adversos , Neoplasia Residual , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/genética , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Radioterapia/efeitos adversos , Recidiva , Transplante Autólogo , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
We studied 526 consecutive post-transplant platelet transfusions to determine the factors associated with response to platelet transfusion in the BMT setting. Poor responses to platelet transfusions occurred frequently, with 310 of the 484 evaluable transfusions (64%) resulting in post-infusion corrected count increments of less than 7500. Factors associated with poor response to platelet transfusion by both univariate and multivariate analysis included, (1) presence of serum lymphocytotoxic antibodies; (2) male sex; (3) body surface area greater than 1.7 m2; (4) transfusion of red cells on the day of the platelet infusion; (5) concurrent administration of steroids; (6) major ABO mismatch between the recipient and the platelet product; and (7) (among women) a history of one or more pregnancies prior to transplant. Paradoxically, a history of greater than 25 blood product exposures prior to transplant, and evidence of prior CMV infection in either the bone marrow donor or recipient were associated with higher CCIs by both univariate and multivariate analysis. Factors that showed little correlation with response to platelet transfusion included, (1) age of the infused platelet product; (2) concurrent fever; (3) recent administration of intravenous immunoglobulin; and (4) absolute neutrophil count at the time of the infusion. The factors associated with response to platelet transfusion in BMT patients appear to be different from those observed in the non-transplant setting.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Transfusão de Plaquetas , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We performed an economic analysis of data from 180 women in a clinical trial of conventional-dose chemotherapy vs high-dose chemotherapy plus stem-cell transplantation for metastatic breast cancer responding to first-line chemotherapy. Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects' clinical trial records. Resources were valued using the Medicare Fee Schedule for inpatient costs at one academic medical center and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. Mean follow-up was 690 days in the transplantation group and 758 days in the conventional-dose chemotherapy group. Subjects in the transplantation group were hospitalized for more days (28.6 vs 17.8, P=0.0041) and incurred higher costs (US dollars 84055 vs US dollars 28169) than subjects receiving conventional-dose chemotherapy, with a mean difference of US dollars 55886 (95% CI, US dollars 47298-US dollars 63666). Sensitivity analyses resulted in cost differences between the treatment groups from US dollars 36528 to US dollars 75531. High-dose chemotherapy plus stem-cell transplantation resulted in substantial additional morbidity and costs at no improvement in survival. Neither the survival results nor the economic findings support the use of this procedure outside of the clinical trial setting.