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1.
Bone Marrow Transplant ; 48(1): 26-31, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22732703

RESUMEN

We investigated the administration of i.v. BU combined with melphalan (Mel) in patients with ALL undergoing allogeneic hematopoietic SCT. Forty-seven patients with a median age of 33 years (range 20-61) received a matched sibling (n=27) or matched unrelated donor transplant (n=20) for ALL in first CR (n=26), second CR (n=13), or with more advanced disease (n=8). BU was infused daily for 4 days, either at a fixed dose of 130 mg/m² (5 patients) or using pharmacokinetic (PK) dose adjustment (42 patients), to target an average daily area-under-the-curve (AUC) of 5000 µmol/min, determined by a test dose of i.v. BU at 32 mg/m². This was followed by a rest day, then two daily doses of Mel at 70 mg/m². Stem cells were infused on the following day. The 2-year OS, PFS and non-relapse mortality (NRM) rates were 35% (95% confidence interval (CI), 23-51%), 31% (95% CI, 21-48%) and 37% (95% CI, 23-50%), respectively. Acute NRM at 100 days was favorable at 12% (95% CI, 5-24%); however, the 2-year NRM was significantly higher for patients older than 40 years, 58% vs 20%, mainly due to GVHD.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Busulfano/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Melfalán/uso terapéutico , Agonistas Mieloablativos/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Acondicionamiento Pretrasplante , Adulto , Factores de Edad , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Busulfano/administración & dosificación , Busulfano/efectos adversos , Quimioterapia Combinada/efectos adversos , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Incidencia , Infusiones Intravenosas , Masculino , Melfalán/efectos adversos , Persona de Mediana Edad , Agonistas Mieloablativos/administración & dosificación , Agonistas Mieloablativos/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/prevención & control , Prevención Secundaria , Análisis de Supervivencia , Texas , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo , Adulto Joven
2.
J Natl Cancer Inst ; 92(3): 225-33, 2000 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-10655439

RESUMEN

BACKGROUND: Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy. PATIENTS AND METHODS: Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests. RESULTS: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy. CONCLUSIONS: No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Metástasis Linfática , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios Prospectivos , Radioterapia Adyuvante , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento
3.
J Clin Oncol ; 15(10): 3171-7, 1997 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9336352

RESUMEN

PURPOSE: Most of the data about high-dose chemotherapy (HDCT) for metastatic breast cancer are derived from phase II studies. The interpretation of these data depends on comparisons with data from properly selected historical control patients treated with standard therapy under similar circumstances. We report the long-term results of patients with metastatic breast cancer who were eligible for HDCT but were treated with doxorubicin-containing standard-dose chemotherapy. PATIENTS AND METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast cancer were evaluated. Using common eligibility criteria for HDCT, we identified patients who would have been candidates for HDCT. We analyzed response rates, progression-free survival (PFS), and overall survival (OS) for all patients, potential HDCT candidates, and noncandidates. RESULTS: A total of 1,581 patients was enrolled onto the 18 studies. Six hundred forty-five were HDCT candidates, and 936 were noncandidates. The complete response rate was 27% for HDCT candidates and 7% for noncandidates; median PFS was 16 and 8 months and median OS was 30 and 17 months, respectively. Survival rates for HDCT candidates and noncandidates, respectively, were 21% and 6% at 5 years and 7% and 2% at 10 years. CONCLUSION: This study suggests that encouraging results of single-arm trials of HDCT could partially be due to selection of patients with better prognoses and further stresses the importance of completing ongoing randomized trials of HDCT to assess the relative efficacy of HDCT in patients with metastatic breast cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Selección de Paciente , Neoplasias de la Mama/mortalidad , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Sesgo de Selección , Tasa de Supervivencia
4.
Br J Haematol ; 97(2): 466-73, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9163617

RESUMEN

The outcome of allogeneic haemopoietic transplants including the rate of immune complications for patients with chronic lymphocytic leukaemia (CLL) refractory to or relapsing after chemotherapy with fludarabine was analysed. Fifteen patients with advanced CLL who received allogeneic transplantation were prospectively analysed. All patients had previously received chemotherapy with fludarabine for 3-15 courses; 12 were refractory. The median number of circulating CD4+ and CD8+ lymphocytes at the time of transplant was 0.49 x 10(9)/l and 0.23 x 10(9)/l, respectively. One patient was transplanted from a one HLA-antigen mismatched unrelated donor. Three others received a one or two antigen mismatched graft and 11 had HLA-identical sibling donors. Patients received cyclosporine or tacrolimus in addition to methotrexate or methylprednisolone for prophylaxis of acute graft-versus-host disease (aGVHD). Fourteen patients engrafted; one patient had graft failure, but recovered after therapy with intravenous immunoglobulin. 13 (87%) achieved complete remission (CR). Nine (53%) remain alive and in CR with a median follow-up of 36 (range 3-60) months. None developed visceral graft-versus-host disease. These data compared favourably to published reports in other leukaemia patients and for patients with CLL who received a comparable immunosuppressive therapy but without prior fludarabine exposure. This data indicates that allogeneic haemopoietic transplantation can induce durable remission in patients with CLL refractory to fludarabine and that it is reasonable to delay transplantation until failure of fludarabine therapy. It also suggests that prior exposure to fludarabine may decrease the incidence of severe aGVHD, possibly through its immunosuppressive effects. Further studies are warranted to evaluate this observation.


Asunto(s)
Antineoplásicos/uso terapéutico , Transfusión de Sangre Autóloga/métodos , Trasplante de Médula Ósea/métodos , Enfermedad Injerto contra Huésped/etiología , Leucemia Linfocítica Crónica de Células B/terapia , Vidarabina/análogos & derivados , Adulto , Antineoplásicos/efectos adversos , Transfusión de Sangre Autóloga/efectos adversos , Trasplante de Médula Ósea/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento , Vidarabina/efectos adversos , Vidarabina/uso terapéutico
5.
Bone Marrow Transplant ; 11(1): 55-9, 1993 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-8094309

RESUMEN

Twenty-six patients with hematologic malignancies (20) or solid tumors (six) were treated with non-glycosylated rhGM-CSF (E. coli) for delayed hematopoietic recovery (granulocytes < 0.1 x 10(9)/l on day 21 or < 0.5 x 10(9)/l on day 28) after autologous marrow or peripheral blood stem cell transplantation. Median pretreatment granulocytes were 0.1 x 10(9)/l (range 0-0.4 x 10(9)/l). Treatment with rhGM-CSF was initiated at 60-250 micrograms/m2 subcutaneously daily with dose escalation every 7 days if there was no response. Within 14 days, 21 (84%) of the 25 evaluable patients achieved granulocytes > 0.5 x 10(9)/l and 17 (68%) had granulocytes > 1.0 x 10(9)/l. For those who responded within 14 days, granulocytes were > 0.5 x 10(9)/l at a median of 3 days (range 1-13) and > 1.0 x 10(9)/l at 6 days (range 2-12). Sixteen of the 23 patients receiving an initial rhGM-CSF dose of 60-125 micrograms/m2 achieved granulocytes > 1.0 x 10(9)/l. Three patients discontinued use of rhGM-CSF because of toxicity, and four patients never recovered despite use of rhGM-CSF doses as high as 1000 micrograms/m2. Graft failure-related mortality was 16% at 4 months after transplantation. These results demonstrate that relatively low doses of non-glycosylated rhGM-CSF administered subcutaneously daily can be used to promote granulocyte recovery in patients with delayed engraftment after autologous transplantation. No beneficial effects were seen on red cell or platelet recovery.


Asunto(s)
Trasplante de Médula Ósea , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Hematopoyesis/efectos de los fármacos , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Transfusión de Sangre Autóloga , Femenino , Glicosilación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos y Macrófagos/química , Granulocitos , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapéutico , Factores de Tiempo
6.
Ann Intern Med ; 115(11): 849-59, 1991 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-1952471

RESUMEN

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/etiología
8.
J Antimicrob Chemother ; 17 Suppl A: 55-66, 1986 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3086277

RESUMEN

The ureidopenicillins (piperacillin, mezlocillin, and azlocillin), aztreonam, and thienamycin are new broad-spectrum beta-lactams with more potent antibacterial activity than the older cephalosporins and penicillins. However, therapy of severe infections with the ureidopenicillins alone is limited by the potential for emergence of resistant organisms, while monotherapy with aztreonam does not provide adequate coverage for Gram-positive aerobic organisms and anaerobes. In combination therapy with the aminoglycosides, the ureidopenicillins may be preferred to carbenicillin or ticarcillin in the treatment of Pseudomonas aeruginosa infections and in institutions with a high prevalence of carbenicillin or ticarcillin-resistant organisms. Double beta-lactam therapy with piperacillin plus either latamoxef (moxalactam) or ceftazidime may be advantageous in patients for whom aminoglycoside toxicity is a concern. Thienamycin is the most promising of the new beta-lactams for single-agent therapy of severe infections but may also be associated with the emergence of resistant P. aeruginosa during monotherapy. In febrile granulocytopenic patients or other severely ill patients at risk of severe P. aeruginosa infections, thienamycin or another antipseudomonal beta-lactam should be combined with an aminoglycoside.


Asunto(s)
Ampicilina/uso terapéutico , Aztreonam/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Tienamicinas/uso terapéutico , Aminoglicósidos/farmacología , Aminoglicósidos/uso terapéutico , Ampicilina/farmacología , Azlocilina/farmacología , Azlocilina/uso terapéutico , Aztreonam/farmacología , Bacterias/efectos de los fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Enterobacteriaceae/efectos de los fármacos , Humanos , Mezlocilina/farmacología , Mezlocilina/uso terapéutico , Piperacilina/farmacología , Piperacilina/uso terapéutico , Pseudomonas aeruginosa/efectos de los fármacos , Tienamicinas/farmacología
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