RESUMEN
Intravenous immunoglobulin is approved for use in allogeneic bone marrow transplant recipients for prevention of graft-versus-host disease (GVHD) and infections, but the minimally effective dose has not been established. In this multicenter, randomized, double-blind trial, patients undergoing allogeneic marrow transplantation were randomized to receive 100 mg/kg, 250 mg/kg, or 500 mg/kg doses of intravenous immunoglobulin. Each dose was given weekly for 90 days and then monthly until 1 year after transplant. Six hundred and eighteen patients were evaluated. Acute GVHD (grades 2-4) occurred in 39% of the patients (80 of 206) in the 100 mg/kg group, 42% of the patients (88 of 208) in the 250 mg/kg group, and in 35% of the patients (72 of 204) in the 500 mg/kg group (P = 0.344). Among patients with unrelated marrow donors, a higher dose of intravenous immunoglobulin (500 mg/kg) was associated with less acute GVHD (P = 0.07). The incidences of chronic GVHD, infection and interstitial pneumonia were similar for all three doses of intravenous immunoglobulin. The dose of intravenous immunoglobulin also had no effect on the types of infection, relapse of hematological malignancy or survival. Except for more frequent chills (P = 0.007) and headaches (P = 0.015) in patients given the 500 mg/kg or 250 mg/kg dose of immunoglobulin, adverse events were similar for all three doses. These results suggest that 100 mg/kg, 250 mg/kg, and 500 mg/kg doses of intravenous immunoglobulin are associated with similar incidences of GVHD and infections in most allogeneic marrow transplants. These results should be considered when designing cost-effective strategies for the use of intravenous immunoglobulin in allogeneic marrow transplants receiving other current regimens for prophylaxis of GVHD and infection.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Médula Ósea/inmunología , Enfermedad Injerto contra Huésped/prevención & control , Inmunoglobulinas Intravenosas/uso terapéutico , Infecciones/epidemiología , Leucemia/terapia , Linfoma/terapia , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Niño , Preescolar , Ciclosporina/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Prueba de Histocompatibilidad , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Terapia de Inmunosupresión/métodos , Depleción Linfocítica , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Análisis de Supervivencia , Factores de Tiempo , Donantes de Tejidos/estadística & datos numéricos , Trasplante HomólogoRESUMEN
In a double-blind, multicenter trial, 541 febrile granulocytopenic patients were randomized to receive either intravenous (iv) clinafloxacin (200 mg every 12 h) or i.v. imipenem (500 mg every 6 h) as empirical monotherapy. More baseline pathogens were susceptible to clinafloxacin (259 [99%] of 262 organisms) than to imipenem (253 [95%] of 265; P=.03). Initial favorable clinical response rates for clinafloxacin (88 [32%] of 272 patients) and imipenem (89 [33%] of 269) were similar. After addition of other antimicrobial agents, overall response rates were 259 (95%) of 272 for clinafloxacin and 251 (93%) of 269 for imipenem. During the study, only 13 clinafloxacin (5%) and 18 imipenem (7%) recipients died. Both drugs were generally well tolerated. Drug-related skin rash occurred more often with clinafloxacin (11% vs. 6%; P=.07), whereas nausea (2% vs. 5%; P=.16), Clostridium-difficile-associated diarrhea (3% vs. 8%; P=.02), and seizures (0% vs. 2%; P=.06) occurred more often with imipenem. These results suggest that clinafloxacin and imipenem have similar efficacy as empirical monotherapy in febrile granulocytopenic patients.
Asunto(s)
Agranulocitosis/tratamiento farmacológico , Antiinfecciosos/uso terapéutico , Fluoroquinolonas , Imipenem/uso terapéutico , Tienamicinas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Agranulocitosis/microbiología , Antiinfecciosos/efectos adversos , Recuento de Células Sanguíneas , Canadá , Método Doble Ciego , Femenino , Humanos , Imipenem/efectos adversos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Tienamicinas/efectos adversos , Resultado del Tratamiento , Estados UnidosRESUMEN
We report one male with testicular cancer and one with lymphoma who received transplants more than 20 years ago. Both are well.
Asunto(s)
Trasplante de Médula Ósea , Linfoma no Hodgkin/terapia , Sobrevivientes , Teratocarcinoma/terapia , Neoplasias Testiculares/terapia , Actividades Cotidianas , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Enfermedades en Gemelos , Estudios de Seguimiento , Humanos , Estado de Ejecución de Karnofsky , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/radioterapia , Masculino , Inducción de Remisión , Teratocarcinoma/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Factores de Tiempo , Donantes de Tejidos , Trasplante Autólogo , Trasplante HomólogoRESUMEN
The outcome of 155 adult aplastic anemia (AA) patients treated with antithymocyte globulin (ATG, Upjohn, Kalamazoo, MI) at University of California, Los Angeles from 1977 to 1988 was evaluated. The median survival of the 146 patients who did not undergo bone marrow transplantation was 5.6 years, with 49% +/- 4% surviving more than 6 years. The most important predictor of survival was positive response to ATG (P < 0.001), which was observed in 48% of patients. Among pretreatment variables, disease severity was the best predictor of survival. Patients with moderate AA (MAA) had significantly better survival than those with severe (SAA) or very severe (VSAA) disease (P = 0.04). The 6-year actuarial survival rates of the three groups were 71% +/- 9%, 48% +/- 7% and 38% +/- 7%, respectively. Cox regression analysis found disease severity to be the only pretreatment variable significantly associated with survival (P = .02). Patient age, sex, disease etiology, concurrent treatment with androgens, or duration of ATG therapy were not associated with differences in survival or response to ATG. Late clonal hematologic complications (ie, myelodysplasia, acute myelogenous leukemia) were observed in 5 of the 77 patients followed for more than 2 years after ATG treatment. In addition, one case of non-Hodgkin's lymphoma and three solid tumors occurred in the ATG-treated patients. The survival of 56 ATG-treated patients with SAA or VSAA between the ages of 16 and 43 did not differ significantly from that of 55 adult AA patients who underwent bone marrow transplant (BMT) during the same time period (P = 0.6). However, 6-year survival rates improved from 43% for patients transplanted before 1984, to 72% for those who underwent BMT between 1984 and 1989. In contrast, there was no difference in the survival rates of patients treated with ATG during these two time periods (46% v 45%, respectively). The results suggest a superior long-term outcome for adult patients with SAA treated with BMT rather than with ATG alone, using current protocols.
Asunto(s)
Anemia Aplásica/terapia , Suero Antilinfocítico/uso terapéutico , Trasplante de Médula Ósea , Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Aplásica/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Análisis de Regresión , Inducción de Remisión , Terapia Recuperativa , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The efficacy of i.v. immunoglobulin plus CMV-seronegative blood products or CMV-seronegative blood products alone for prevention of CMV infection, symptomatic CMV disease, other infections and GVHD after BMT was evaluated in a randomized, controlled trial. Fifty-one CMV-seronegative allogeneic BMTs with a CMV-seronegative or CMV-seropositive marrow donor were randomly assigned to receive either i.v. immunoglobulin (1.0 g/kg once weekly for 120 days after transplant) plus CMV-seronegative blood products or CMV-seronegative blood products alone. CMV infection occurred in 2 of 25 patients (7%) receiving i.v. immunoglobulin plus CMV-seronegative blood and in 2 of 23 patients (9%) receiving CMV-seronegative blood alone. All CMV infections were asymptomatic and characterized by viral excretion with or without CMV seroconversion. There were no cases of CMV-related interstitial pneumonia. Grade > or = II GVHD was less frequent in patients given i.v. immunoglobulin (5 of 25 patients (20%) vs. 11 of 23 patients (48%), p = 0.04). The number of bacterial and fungal infections was similar in both groups. Fewer non-CMV viral infections (9 of 27 patients (33%) vs. 15 of 24 patients (63%), p = 0.03) and fewer deaths associated with infection (1 of 27 patients (4%) vs. 5 of 24 patients (21%), p = 0.07) occurred in recipients of immunoglobulin. Neither survival nor risk of leukemia relapse was changed by the immunoglobulin. The high doses of i.v. immunoglobulin were well tolerated. These results suggest that CMV-seronegative blood products alone prevent most CMV infections and CMV disease in CMV-seronegative allogeneic BMT recipients, even when the marrow donor is CMV-seropositive.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Transfusión Sanguínea , Trasplante de Médula Ósea , Infecciones por Citomegalovirus/prevención & control , Inmunoglobulinas Intravenosas/uso terapéutico , Adolescente , Adulto , Infecciones Bacterianas/epidemiología , Transfusión Sanguínea/normas , Trasplante de Médula Ósea/mortalidad , Trasplante de Médula Ósea/normas , Niño , Preescolar , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/transmisión , Femenino , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Incidencia , Enfermedades Pulmonares Intersticiales/epidemiología , Enfermedades Pulmonares Intersticiales/prevención & control , Masculino , Persona de Mediana Edad , Micosis/epidemiología , Estudios Prospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of fluconazole for prevention of fungal infections. DESIGN: A randomized, placebo-controlled, double-blind, multicenter trial. PATIENTS: Adults (257) undergoing chemotherapy for acute leukemia. INTERVENTION: Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity. MEASUREMENTS: Fungal colonization, proven superficial or invasive fungal infection, empiric antifungal therapy with amphotericin B, drug-related side effects, and mortality. MAIN RESULTS: Fluconazole decreased fungal colonization (83 of 122 [68%] placebo patients compared with 34 of 119 [29%] fluconazole patients colonized at end of prophylaxis, P < 0.001) and proven fungal infections (27 of 132 [21%] placebo patients compared with 11 of 123 [9%] fluconazole patients infected, P = 0.02). Superficial fungal infections occurred in 20 of 132 (15%) placebo patients but in only 7 of 123 (6%) fluconazole patients (P = 0.01), whereas invasive fungal infections developed in 10 of 132 (8%) placebo patients and in 5 of 123 (4%) fluconazole patients (P = 0.3). Fluconazole was especially effective in eliminating colonization and infection by Candida species other than Candida krusei (66 of 122 [64%] placebo patients colonized at end of prophylaxis compared with 11 of 119 [9%] fluconazole patients, P < 0.001; 22 of 132 [17%] placebo patients infected compared with 7 of 123 [6%] fluconazole patients, P = 0.005). Aspergillus infections were infrequent in both fluconazole (3 cases) and placebo groups (3 cases). The use of amphotericin B, the incidence of drug-related side effects, and overall mortality were similar in both study groups. CONCLUSION: Prophylactic fluconazole prevents colonization and superficial infections by Candida species other than Candida krusei in patients undergoing chemotherapy for acute leukemia and is well tolerated. Fluconazole could not be clearly shown to be effective for preventing invasive fungal infections, reducing the use of amphotericin B, or decreasing the number of deaths.
Asunto(s)
Fluconazol/uso terapéutico , Leucemia/complicaciones , Micosis/prevención & control , Neutropenia/complicaciones , Infecciones Oportunistas/prevención & control , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Fluconazol/efectos adversos , Hongos/efectos de los fármacos , Hongos/crecimiento & desarrollo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of ganciclovir for prevention of cytomegalovirus (CMV) infection and disease. DESIGN: A randomized, placebo-controlled, double-blind trial. SETTING: University-affiliated bone marrow transplant center. PATIENTS: Cytomegalovirus-seropositive allogeneic bone marrow transplant recipients. INTERVENTIONS: Random assignment to receive either a placebo or ganciclovir at a dose of 2.5 mg/kg body weight every 8 hours for 1 week before transplant and then at a dose of 6 mg/kg once per day, Monday through Friday, after transplant when the post-transplant neutrophil count reached 1.0 x 10(9)/L. MEASUREMENTS: Cytomegalovirus infection (positive culture, seroconversion, positive histologic findings), CMV disease (pneumonia, gastroenteritis, the wasting syndrome), and study-drug toxicity. RESULTS: Cytomegalovirus infection developed in 25 of 45 placebo patients (56%) but in only 8 of 40 ganciclovir patients (20%) (P < 0.001). Cytomegalovirus disease may also have occurred less often in the ganciclovir patients (4 of 40 patients [10%] versus 11 of 45 patients [24%]; P = 0.09). The probability of CMV disease occurring within the first 120 days after transplantation was 0.29 among the placebo patients but only 0.12 among ganciclovir patients (P = 0.06). Reversible neutropenia was the only appreciable toxicity related to ganciclovir and required interruption of the study drug after transplant in 25 of 43 ganciclovir patients (58%) and in 13 of 47 placebo patients (28%) (P = 0.005). Overall survival was similar in both the placebo patients (29 of 45 [64%]) and ganciclovir patients (28 of 40 [70%]; P > 0.2). CONCLUSIONS: Prophylactic ganciclovir, started before transplant and continued after recovery of the post-transplant neutrophil count, reduces the incidence and severity of CMV infection in CMV-sero-positive bone marrow transplant recipients but is frequently associated with neutropenia.
Asunto(s)
Trasplante de Médula Ósea , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/uso terapéutico , Infecciones Oportunistas/prevención & control , Adolescente , Adulto , Trasplante de Médula Ósea/mortalidad , Citomegalovirus/efectos de los fármacos , Infecciones por Citomegalovirus/diagnóstico , Método Doble Ciego , Femenino , Ganciclovir/efectos adversos , Herpesvirus Humano 3/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Pruebas Serológicas , Simplexvirus/efectos de los fármacos , Tasa de Supervivencia , Esparcimiento de Virus/efectos de los fármacosRESUMEN
Hemolysis most commonly occurs following bone marrow transplant when there is "minor" ABO blood group incompatibility between donor and recipient. The hemolysis has been attributed to destruction of the patient's incompatible erythrocytes by donor-derived anti-A and/or anti-B antibody produced from "passenger" immunocompetent donor lymphocytes. Extraordinary transfusion requirements of group O erythrocytes in a series of patients receiving unrelated minor ABO-incompatible marrow grafts led us to investigate whether this mechanism could account for the extent of hemolysis observed. In seven consecutive minor ABO-incompatible unrelated-donor bone marrow transplant recipients receiving cyclosporine without posttransplant methotrexate, we observed excessive hemolysis. For cases in this index group, a strongly reactive donor-derived ABO blood group antibody was identified coincident with development of hemolysis. Transfusion requirements in the first three patients (26 U of group O erythrocytes each) greatly exceeded the recipient's volume of incompatible erythrocytes, indicating that lysis of transfused group O erythrocytes was also occurring. Pretransplant erythrocyte exchange transfusion with group O erythrocytes performed in the four subsequent patients decreased the severity of hemolysis, but did not prevent it. Among minor ABO-incompatible marrow graft recipients, an analysis of variance demonstrated effects on transfusion requirements due to donor-recipient relationship being unrelated (P less than .002) and the use of posttransplant methotrexate (P = .0001), and there was interaction between these two factors (P less than .001). Bone marrow transplants from unrelated donors resulted in an exaggerated immune response to ABO blood group antigens, which was associated with hemolysis of transfused group O erythrocytes, as well as the patient's ABO-incompatible erythrocytes. This serious complication may be prevented by posttransplant immunosuppression with methotrexate.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Transfusión de Componentes Sanguíneos , Incompatibilidad de Grupos Sanguíneos , Trasplante de Médula Ósea , Ciclosporina/uso terapéutico , Hemólisis/inmunología , Metotrexato/uso terapéutico , Adulto , Anemia Aplásica/cirugía , Anticuerpos/sangre , Prueba de Coombs , Humanos , Terapia de Inmunosupresión , Leucemia/cirugía , Persona de Mediana Edad , Síndromes Mielodisplásicos/cirugíaRESUMEN
PURPOSE: Despite substantial progress in the treatment of acute myeloid leukemia (AML), fewer than 25% of patients survive free of leukemia for more than 5 years without allogeneic bone marrow transplantation (BMT). In this study we analyzed the results of one or more cycles of high-dose cytarabine-based consolidation chemotherapy as compared with allogeneic BMT in first remission. PATIENTS AND METHODS: The results in 28 adult patients, aged 16 to 45 years, who underwent a closely HLA-matched BMT for AML in first remission were compared with those in 54 consecutive, age-matched, adult patients treated with one or more cycles of high-dose, cytarabine-based consolidation chemotherapy. RESULTS: After a median follow-up of 4 years, the actuarial risk of leukemic relapse was considerably lower in the transplant group than in the group treated with consolidation chemotherapy (32% +/- 26% v 60% +/- 14%; P = .05). Treatment-related mortality, however, was much higher in the group treated with BMT (32% v 6%, P = .002). The actuarial disease-free survival at 5 years was not significantly different for the two groups (45% +/- 24% v 38% +/- 14%). CONCLUSIONS: Our results show that BMT in first remission AML did not offer a disease-free survival advantage over intensive postremission consolidation chemotherapy. Larger studies are needed to identify patients who might benefit most from BMT.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/cirugía , Análisis Actuarial , Adolescente , Adulto , Citarabina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Análisis de Supervivencia , Trasplante HomólogoRESUMEN
OBJECTIVE: To compare the efficacy, toxicity, and cost-effectiveness of double beta-lactam therapy with monotherapy. DESIGN: A randomized, controlled trial. PATIENTS: Febrile, granulocytopenic patients (429). INTERVENTIONS: Patients were randomly assigned to receive iv cefoperazone (3 g every 12 hours) plus piperacillin (75 mg/kg body weight every 6 hours), ceftazidime (2 g every 8 hours) plus piperacillin (75 mg/kg every 6 hours), or imipenem alone (1.0 g or 0.5 g every 6 hours). Patients also received prophylactic vitamin K. MEASUREMENTS: Clinical improvement, eradication of the infecting organism, and toxicity in 403 evaluable patients with one or more infections. MAIN RESULTS: Cefoperazone and ceftazidime, when given in combination with piperacillin, were equally effective (response rates of 75% (104 of 138 patients) and 74% (101 of 137 patients), respectively). Monotherapy with imipenem had a response rate of 82% (111 of 136 patients) and was as effective as double beta-lactam therapy. Overall antibiotic-related toxicity was minimal, although seizures were associated with high doses of imipenem. Seizures occurred in 3 of 29 patients (10.3%) who were receiving 4 g/d of imipenem, in 3 of 136 patients (2.2%) who were receiving cefoperazone plus piperacillin, in 0 of the 132 patients who were receiving ceftazidime plus piperacillin, and in 1 of 106 patients (0.9%) who were receiving 2 g/d of imipenem (P less than 0.005). The 2-g daily dose of imipenem was as effective as the 4-g daily dose. Diarrhea was more frequent in patients receiving cefoperazone, whereas nausea occurred more often with imipenem. No antibiotic-related hemorrhage or nephrotoxicity was observed. Superinfections caused by beta-lactam-resistant, gram-negative bacilli were uncommon but occurred more frequently with double beta-lactam therapy than with imipenem monotherapy (11 of 268 patients compared with 1 of 135 patients; P = 0.06). Xanthomonas maltophilia superinfections occurred only in patients receiving imipenem (3 of 135 patients compared with 0 of 268 patients; P = 0.03). Imipenem monotherapy was the least expensive therapy. CONCLUSIONS: Cefoperazone and ceftazidime were equally effective when used in combination antibiotic therapy with piperacillin. Twice-daily cefoperazone is less expensive than ceftazidime given three times daily. Monotherapy with imipenem, at a daily dose of 2 g, is as efficacious as double beta-lactam therapy and costs less than combination therapy.
Asunto(s)
Agranulocitosis/complicaciones , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Fiebre/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antibacterianos/efectos adversos , Antibacterianos/economía , Infecciones Bacterianas/etiología , Cefoperazona/uso terapéutico , Ceftazidima/uso terapéutico , Costos y Análisis de Costo , Quimioterapia Combinada/uso terapéutico , Femenino , Fiebre/etiología , Fiebre/microbiología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Imipenem/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Piperacilina/uso terapéutico , Sobreinfección/etiologíaRESUMEN
Cytomegalovirus (CMV) infection occurs in approximately 50% of all recipients of allogeneic bone marrow transplants and is seen more frequently in CMV-seropositive patients than in CMV-seronegative patients. Sources of infection include reactivation of latent endogenous virus, blood products from CMV-seropositive blood donors, and the use of marrow from a CMV-seropositive donor for a CMV-seronegative recipient. The most common and severe clinical syndrome associated with CMV infection in allogeneic transplant recipients is interstitial pneumonia, which occurs in approximately 15% of patients. Risk factors for CMV pneumonia include old age, conditioning with total-body irradiation, and severe graft-vs.-host disease. The rapid diagnosis of CMV pneumonia has been facilitated by immunochemical staining of bronchoalveolar lavage fluid or by centrifugation of cell cultures with CMV monoclonal antibodies. The treatment of CMV pneumonia remains problematic, but therapy with a combination of intravenous immune globulin (IVIG) plus ganciclovir has resulted in survival rates substantially better than those achieved in previous trials of antiviral therapy. In CMV-seronegative patients, CMV infection and pneumonia can be prevented or modified by the use of CMV-seronegative blood products and IVIG. IVIG may also have the additional benefits of preventing other infectious complications and graft-vs.-host disease in patients receiving CMV-seronegative blood products. For CMV-seropositive patients, effective prophylaxis for CMV reactivation and pneumonia has not yet been established, but a clinical trial of prophylactic ganciclovir is now under way.
Asunto(s)
Trasplante de Médula Ósea , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/terapia , Humanos , Fibrosis Pulmonar/etiología , Trasplante HomólogoRESUMEN
Thirty-four patients received bone marrow transplants from unrelated donors. Donors and recipients were phenotypically matched for 6 of 6 HLA-A, B, and DR antigens in 27 cases and at 5 of 6 antigens in 7 cases. Twenty-three patients had leukemia, six had myelodysplasia, and five had aplastic anemia. Twenty-four patients had durable engraftment. Five died of sepsis prior to engraftment. Five patients failed to engraft; 2 of these patients had autologous bone marrow recovery. Seventeen patients developed grade greater than or equal to II acute graft-versus-host disease for an actuarial probability of 67 +/- 20%. The severity of acute graft-versus-host disease and its mortality appeared increased for recipients matched for 5 of 6 HLA-A, B, and DR antigens. Of the 34 patients, 13 (38%) are alive; actuarial survival beyond 6 months is 44 +/- 17%. None of the 25 leukemia and myelodysplasia patients achieving engraftment have relapsed. For leukemia and myelodysplasia recipients of 6 of 6 HLA-matched grafts, actuarial survival at 6 months was 55 +/- 21% compared with 14 +/- 26% for recipients matched for 5 of 6 HLA loci (P = 0.19). Infection and acute graft-versus-host disease were the primary causes of death in the engrafted patients. Survival for aplastic anemia patients was 20%. Late deaths due to pneumonia and bronchiolitis obliterans occurred after one year in 2 patients. Closely matched unrelated donor bone marrow transplants are associated with a higher incidence of graft failure and graft-versus-host disease than typically reported for transplants from HLA-identical siblings, but these preliminary data suggest a lower rate of relapse.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Médula Ósea/inmunología , Leucemia/terapia , Síndromes Mielodisplásicos/terapia , Enfermedad Aguda , Enfermedad Crónica , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/inmunología , Histocompatibilidad , Humanos , Prueba de Cultivo Mixto de Linfocitos , Análisis de SupervivenciaRESUMEN
Twenty-nine patients with severe aplastic anemia were entered into a study of pre- and posttransplant immunosuppressive therapy for bone marrow transplantation. Four of twenty-five previously transfused recipients prepared with cyclophosphamide 200 mg/kg and total-lymphoid irradiation 3 Gy experienced graft failure, indicating that this regimen was inadequate to ensure sustained engraftment. Posttransplant treatment with cyclosporine and methotrexate resulted in an actuarial incidence for grade greater than or equal to 2 graft-versus-host disease of 22 +/- 16%. Actuarial survival was 78 +/- 15%. These data indicate that more effective treatment is necessary to prevent graft failure, but since many patients can be successfully retransplanted, overall survival is comparable to other recent studies.
Asunto(s)
Anemia Aplásica/cirugía , Trasplante de Médula Ósea/métodos , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/prevención & control , Adolescente , Adulto , Niño , Preescolar , Ciclofosfamida/uso terapéutico , Ciclosporinas/uso terapéutico , Femenino , Estudios de Seguimiento , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/efectos de la radiación , Humanos , Lactante , Irradiación Linfática , Masculino , Metotrexato/uso terapéuticoRESUMEN
INTRODUCTION: The efficacy and safety of oral ofloxacin were compared with those of vancomycin/polymyxin for prophylaxis of bacterial infections in granulocytopenic patients undergoing chemotherapy for hematologic malignancy. PATIENTS AND METHODS: Antimicrobial prophylaxis was begun at the time of initiation of chemotherapy. Thirty patients received ofloxacin tablets (300 mg orally every 12 hours) plus a nystatin suspension. Thirty-two patients received vancomycin capsules (500 mg orally every eight hours) and polymyxin capsules (100 mg orally every eight hours) plus a nystatin suspension. RESULTS: In the group of patients receiving ofloxacin, there were a lower number of acquired gram-negative bacillary organisms per patient (0.13 versus 1.37, p less than 0.00005), fewer patients with documented infection (11 of 30 versus 21 of 32, p = 0.04), and fewer cases of gram-negative septicemia (zero of 30 versus five of 32, p = 0.05). Ofloxacin was also better tolerated (24 of 30 versus 10 of 32 patients highly compliant, p = 0.01) and associated with fewer gastrointestinal side effects (one of 30 versus nine of 32 patients with gastrointestinal side effects, p = 0.01) than vancomycin/polymyxin. However, except for a reduction of Staphylococcus aureus colonization and infection by ofloxacin, neither ofloxacin nor vancomycin/polymyxin was effective in eliminating colonization or infection with viridans group streptococci, coagulase-negative staphylococci, or other gram-positive organisms. Only three isolates of ofloxacin-resistant gram-negative bacteria (Pseudomonas fluorescens, Pseudomonas putida, and Enterobacter aerogenes) were isolated from surveillance cultures, but none caused infection. CONCLUSION: These results suggest that oral ofloxacin is a more tolerable and efficacious alternative to vancomycin/polymyxin for prevention of serious gram-negative bacillary infections in granulocytopenic patients. More effective prophylaxis of gram-positive infections, however, is still needed.
Asunto(s)
Agranulocitosis/microbiología , Infecciones Bacterianas/prevención & control , Ofloxacino/uso terapéutico , Polimixinas/administración & dosificación , Vancomicina/administración & dosificación , Adolescente , Adulto , Anciano , Agranulocitosis/etiología , Bacterias/aislamiento & purificación , Infecciones Bacterianas/microbiología , Sistema Digestivo/microbiología , Quimioterapia Combinada , Femenino , Hongos/aislamiento & purificación , Humanos , Leucemia/complicaciones , Masculino , Persona de Mediana Edad , Nasofaringe/microbiología , Ofloxacino/administración & dosificación , Polimixinas/uso terapéutico , Vancomicina/uso terapéuticoRESUMEN
One hundred ninety-six patients with acute myelogenous leukemia (AML) were treated with intensive induction chemotherapy using similar daunorubicin/cytarabine/thioguanine regimens. Treatment results of 44 patients who had a documented preleukemic syndrome or cytopenia present for more than 2 months before developing over AML were compared with 152 patients with de novo AML. Eighteen (41%) patients with preleukemia evolving into AML achieved complete remission compared with 111 (73%) patients with de novo AML (P less than .01). Patients with preleukemia-AML had a significantly longer period to recovery of granulocytes. Multivariate analysis indicated that presence of a previous preleukemic syndrome and advancing age were independent poor prognostic indicators for achieving remission. For patients who achieved remission, disease-free survival and overall survival were also inferior for patients with previous preleukemia; disease-free survival was 17 +/- 17% at 3 years compared with 29 +/- 10% in patients with de novo AML (P = .02). These data indicate that intensive chemotherapy has limited efficacy in patients with AML following a preleukemic syndrome. Durable remissions may be achieved in some patients.
Asunto(s)
Leucemia Mieloide Aguda/tratamiento farmacológico , Preleucemia/complicaciones , Factores de Edad , Anemia Aplásica/complicaciones , Anemia Refractaria con Exceso de Blastos/complicaciones , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Humanos , Leucemia Mieloide Aguda/complicaciones , Análisis Multivariante , Defectos del Tubo Neural/complicaciones , Pronóstico , Análisis de Regresión , Tasa de Supervivencia , Tioguanina/administración & dosificaciónAsunto(s)
Aciclovir/análogos & derivados , Antivirales/uso terapéutico , Trasplante de Médula Ósea , Infecciones por Citomegalovirus/tratamiento farmacológico , Terapia de Inmunosupresión/efectos adversos , Aciclovir/efectos adversos , Aciclovir/sangre , Aciclovir/uso terapéutico , Adulto , Antivirales/efectos adversos , Citomegalovirus/efectos de los fármacos , Infecciones por Citomegalovirus/etiología , Femenino , Ganciclovir , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/etiologíaRESUMEN
Infections continue to be common complications of bone marrow transplantation, but recent advances have improved their outcome. Oral chemoprophylaxis with the fluoroquinolones has reduced gram-negative infections during periods of granulocytopenia, while new triazole drugs show promise for improving antifungal prophylaxis. Similarly, recombinant hematopoietic growth factors may reduce infections by shortening the period of post-transplant granulocytopenia. The efficacy of double beta-lactam antibiotic therapy or monotherapy with imipenem has obviated the need to use aminoglycosides in the empiric treatment of febrile patients receiving cyclosporine or other nephrotoxic agents. Treatment of post-transplant interstitial pneumonia associated with cytomegalovirus (CMV) remains problematic, but recent results using the combination of ganciclovir plus intravenous immune globulin have been favorable. In CMV-seronegative patients, CMV infections and pneumonia can be prevented or modified by using CMV-seronegative blood products and intravenous immune globulin. Intravenous immune globulin also has the additional benefits of modifying graft versus host disease and preventing late bacterial infections after marrow engraftment. In CMV-seropositive patients, prophylactic ganciclovir may prevent CMV reactivation and pneumonia and is the subject of an ongoing controlled clinical trial.
Asunto(s)
Trasplante de Médula Ósea , Infecciones Oportunistas/terapia , Complicaciones Posoperatorias/terapia , HumanosRESUMEN
Patients with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis (FGS) who develop end-stage renal disease are at risk for recurrence of the disease following renal transplantation. Recurrence of the nephrotic syndrome in renal allografts of two children with primary FGS was successfully controlled by plasma exchange. This report suggests that plasma exchange instituted early in the course of recurrent nephrotic syndrome may be beneficial in some patients with steroid-resistant nephrotic syndrome and FGS.
Asunto(s)
Trasplante de Riñón , Síndrome Nefrótico/terapia , Intercambio Plasmático , Adolescente , Niño , Humanos , Masculino , Síndrome Nefrótico/etiología , Recurrencia , Trasplante Homólogo/efectos adversosRESUMEN
PURPOSE: Acyclovir and high doses of intramuscular leukocyte interferon have been shown to prevent dissemination of herpes zoster in cancer patients with localized herpes zoster. With the availability of recombinant interferon, we decided to conduct a multicenter, placebo-controlled, double-blind trial of intramuscular recombinant interferon alpha-2a to assess its efficacy and safety in the treatment of localized herpes zoster in immunosuppressed patients with cancer. PATIENTS AND METHODS: Immunosuppressed cancer patients with localized herpes zoster were randomly assigned to receive placebo, 36 X 10(6) units of recombinant interferon alpha-2a per day, or 68 X 10(6) units of recombinant interferon alpha-2a per day. Due to frequent adverse effects, the 68 X 10(6) unit dose of interferon was discontinued prior to conclusion of the trial. RESULTS: Dissemination of herpes zoster occurred in 14 of the 24 patients (58 percent) who received placebo but in only four of 24 recipients (17 percent) of 36 X 10(6) units of interferon per day (p = 0.003). Adverse effects (fever, chills, headaches, gastrointestinal irritability, fatigue, and myalgias) were more common or severe in interferon-treated patients. CONCLUSION: These results suggest that interferon modifies the severity of herpes zoster in immunosuppressed patients with cancer but is associated with frequent side effects.