RESUMEN
This study aimed to analyse the association of gene polymorphisms with the outcome of allogeneic haematopoietic stem cell transplantation. We studied 122 donor/recipient pairs who received HLA-identical transplants from siblings at the Universidade Estadual de Campinas, Brazil, between June 1996 and June 2006. Donor/recipient alleles for TNFA-238 and IL2-330/+166 single-nucleotide polymorphisms (SNP) were analysed by PCR-SSP. No association was observed between the risk of acute graft-versus-host disease (GVHD) and these SNP. However, our findings suggest that the polymorphism of promoter gene TNFA-238GA is associated with the occurrence and severity of chronic GVHD. The probability of chronic GVHD in patients with GA genotype at position -238 of TNFA gene is 91.7% in contrast to 59.4% in patients with GG genotype (P = 0.038). In patients with donor GA genotype the probability of chronic GVHD is 90.8%, and 57.9% in patients with donor GG genotype (P = 0.038). The probability of extensive chronic GVHD in patients with TNFA-238GA is 91.7% compared with 46.3% in patients with TNFA-238GG (P = 0.0046). In patients with donor GA genotype at position -238 of the TNFA gene, it is 81.7%, compared with 44.5% in patients with donor GG genotype (P = 0.016). However, further studies with more patients are required to identify cytokine gene polymorphisms and their association with transplant-related complication in Brazil, particularly due to ethnic background, the relatively low power of detection of genetic markers of this study, and the complexity of the MHC region.
Asunto(s)
Enfermedad Injerto contra Huésped/genética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Interleucina-2/genética , Polimorfismo Genético/genética , Factor de Necrosis Tumoral alfa/genética , Adolescente , Adulto , Brasil , Niño , Femenino , Genotipo , Enfermedad Injerto contra Huésped/inmunología , Humanos , Lactante , Interleucina-2/inmunología , Leucemia/genética , Leucemia/terapia , Masculino , Persona de Mediana Edad , Polimorfismo Genético/inmunología , Hermanos , Donantes de Tejidos , Trasplante Homólogo , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
The objective of the study was to evaluate the frequency and clinical characteristics of ocular complications and their risk factors, as well as autologous serum tears (AST) for the treatment of dry eye in these patients. Data from the files of 124 patients who had undergone allogeneic haematopoietic progenitor cell transplantation (HPCT) were evaluated. In addition, 33 HPCT patients were examined and their data were compared with controls. Analysis of tears and AST was performed. Dry eye manifestation occurred in 32% of patients and was positively correlated with age over 27 years (P = 0.05), peripheral blood progenitor cell transplant (P = 0.002), chronic graft-versus-host disease (P = 0.0027), and chronic or acute myeloid leukaemia (P = 0.001). Dry mouth and Schirmer test < 5 mm were predictive factors for dry eye in HPCT patients (P = 0.002 and odds ratio 3.9 and P = 0.007, odds ratio = 5.9, respectively). Microbiological analysis revealed that six of 11 AST samples were contaminated after 30 days of use. The present study supports the role of potential risk factors for ocular complications and key elements to detect alterations in the tear film from HPCT patients. In addition, AST contamination must be considered after longer periods of use.
Asunto(s)
Síndromes de Ojo Seco , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Soluciones Oftálmicas/uso terapéutico , Suero , Adolescente , Adulto , Factores de Edad , Niño , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas/química , Soluciones Oftálmicas/aislamiento & purificación , Factores de RiesgoRESUMEN
Salivary gland dysfunction is a common sequela of hematopoietic progenitor cell transplantation (HPCT). The investigation of major salivary gland dysfunction with sodium pertechnetate scintigraphy is a non-invasive method that provides images of the parotid and submandibular glands. In this prospective trial, 20 HPCT patients were submitted to scintigraphic study with 99mTc-pertechenate and 67Ga in order to evaluate the major salivary glands early involvement following HPCT. Major salivary glands were evaluated prior to HCPT as well as at Days +30, +60 and +100 post transplant. Major salivary glands uptake and clearance of 99mTc-pertechenate results did not demonstrate any functional differences between pre- versus post transplant periods. Results of the 67Ga scan revealed inflammatory infiltration following HPCT, primarily in submandibular glands, suggest a persistent involvement of major salivary glands up to Day +100 after HPCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Cintigrafía/métodos , Glándulas Salivales/diagnóstico por imagen , Glándulas Salivales/lesiones , Trasplante Homólogo/métodos , Adulto , Femenino , Galio/metabolismo , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Glándulas Salivales/metabolismo , Glándula Submandibular/metabolismo , Tecnecio/metabolismo , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Xerostomía/etiología , Xerostomía/metabolismoRESUMEN
This prospective multicenter randomized trial compares conventional with early intensification with high-dose sequential chemotherapy (HDS) and autologous stem cell transplantation (ASCT) as frontline therapy in high-risk non-Hodgkin lymphomas (NHL). Newly diagnosed patients with aggressive high-risk [intermediate-high (HI) and high-risk (HR)] NHL according to the international prognosis index (IPI) were randomized to receive 12-week VACOP-B (arm A, 27 patients) or 6-week VACOP-B followed by HDS and ASCT (arm B, 29 patients). Complete remission rate was 52% in arm A and 55% in B. Nine patients (16%) died early due to progression. According to intention-to-treat, with a median follow-up of 23 months, the 5-year actuarial overall survival, progression-free survival and disease-free survival in arms A and B were 47 and 40% (p = nonsignificant), 47 and 30% (p = nonsignificant), and 97 and 47% (p = 0.02), respectively. Abbreviated chemotherapy followed by intensification with HDS-ASCT does not seem to be superior to conventional chemotherapy in HI/HR aggressive NHL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma no Hodgkin/terapia , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Pronóstico , Inducción de Remisión , Factores de Riesgo , Trasplante Autólogo , Vincristina/administración & dosificaciónRESUMEN
Fusarium species are hyaline moulds belonging to the hyalohyphomycosis group that are usually found in the soil and plants. This organism has emerged as a cause of disseminated invasive disease. The correlation between in vitro value and clinical efficacy is low and many patients remain unresponsive to treatment despite in vitro susceptibility. We determined growth control for Fusarium solani using the BioCell-Tracer system that measures the growth rate of a single fungal hypha, and the effect of different concentrations of amphotericin B and itraconazole. The MIC for these two drugs was also determined by a broth microdilution technique, using RPMI 1640. Different MICs for amphotericin B were obtained by the two different methods. This paper describes a case of infection due to Fusarium solani in an allogeneic bone marrow transplanted patient, the microbiological diagnostic, antifungal susceptibility tests for conidia and hypha and clinical correlation.
Asunto(s)
Anfotericina B/farmacología , Antifúngicos/farmacología , Fusarium/efectos de los fármacos , Micosis/microbiología , Sepsis/microbiología , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , ADN de Hongos/química , ADN de Hongos/genética , Resultado Fatal , Femenino , Fusarium/crecimiento & desarrollo , Fusarium/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Micosis/tratamiento farmacológico , Embarazo , Complicaciones Infecciosas del Embarazo/microbiología , Sepsis/tratamiento farmacológicoRESUMEN
Busulfan was added at the dose of 4 mg/kg to 200 mg/kg cyclophosphamide in 81 patients (3-53 years, median 24) with aplastic anemia to reduce graft rejection. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine-methotrexate. The number of prior transfusions was 0-276 (median 26), and 48% had received prior immunosuppressive therapy. Two patients experienced primary graft failure, and 10 secondary rejection at 28-1001 days (median 317 days). The cumulative incidence of rejection was 22%; for heavily transfused patients (>/=50 U) it was 43% compared to 16% for the rest (P=0.06). Overall survival rate at 8 years was 56%; patients who received 15 transfusions was 78 and 50%, respectively (P=0.01), whereas it was 67 and 28% for 50 transfusions, respectively (P=0.002). In multivariate analysis, higher number of prior transfusions, shorter period of immunosuppression with cyclosporine and GVHD were associated with inferior survival; moreover, a higher risk of graft rejection were associated with a higher number of prior transfusions and a trend was observed for a shorter cyclosporine administration. Low-dose busulfan is feasible and may be helpful in patients exposed to <50 transfusions. However, rejection remains a significant problem, mainly in heavily transfused patients.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Médula Ósea/métodos , Busulfano/administración & dosificación , Ciclofosfamida/administración & dosificación , Rechazo de Injerto/prevención & control , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anemia Aplásica/complicaciones , Anemia Aplásica/mortalidad , Trasplante de Médula Ósea/efectos adversos , Causas de Muerte , Niño , Preescolar , Quimioterapia Combinada , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/mortalidad , Humanos , Persona de Mediana Edad , Análisis de Supervivencia , Acondicionamiento Pretrasplante/mortalidad , Trasplante HomólogoRESUMEN
Bone marrow transplant recipients are highly susceptible to opportunistic fungal infections. This is the report, of the first case of a Chaetomium systemic infection described in Brazil. A 34 year-old patient with chronic myeloid leukemia underwent an allogeneic sibling matched bone marrow transplant. Seven months later, he developed systemic infection with enlargement of the axillary and cervical lymph nodes. Culture of the aspirates from both lymph nodes yielded Chaetomium globosum. The infection was successfully treated with amphotericin B. The increasing population of immunosupressed patients requires a careful microbiologic investigation for uncommon fungal infections.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Chaetomium/aislamiento & purificación , Micosis/inmunología , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Resultado Fatal , Humanos , Huésped Inmunocomprometido , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Ganglios Linfáticos/microbiología , Masculino , Micosis/tratamiento farmacológico , Micosis/microbiologíaRESUMEN
The feasibility of allogeneic bone marrow transplantation (alloBMT) in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years), 684 (60.1%) were males and 454 (39.9%) were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8%) candidates had full match donors; 352/1138 (30.8%) were eligible for alloBMT. Only 235 of 352 (66.7%) were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3%); monthly family income ranged from US$60 (7%) to more than US$400 (36%). Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30%, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil.
Asunto(s)
Enfermedades de la Médula Ósea/terapia , Trasplante de Médula Ósea/estadística & datos numéricos , Histocompatibilidad , Donadores Vivos/provisión & distribución , Hermanos , Adolescente , Adulto , Enfermedades de la Médula Ósea/mortalidad , Trasplante de Médula Ósea/mortalidad , Brasil/epidemiología , Niño , Preescolar , Escolaridad , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Socioeconómicos , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
The feasibility of allogeneic bone marrow transplantation (alloBMT) in a developing country has not yet been demonstrated. Many adverse factors including social and economic limitations may reduce the overall results of this complex and expensive procedure. Our objective was to characterize the most important clinical, social and economic features of candidates for transplantation and their potential donors as well as the influence of these factors on overall survival in a retrospective and exploratory analysis at a university hospital. From July 1993 to July 2001, candidates for BMT were referred to the Bone Marrow Transplantation Unit by Hematology and Oncology Centers from several regions of Brazil. A total of 1138 patients were referred to us as candidates for alloBMT. Median age was 25 years (range: 2 months-60 years), 684 (60.1 percent) were males and 454 (39.9 percent) were females. The clinical indications were severe aplastic anemia and hematological malignancies. From the total of 1138 patients, 923 had HLA-typing; 497/923 (53.8 percent) candidates had full match donors; 352/1138 (30.8 percent) were eligible for alloBMT. Only 235 of 352 (66.7 percent) were transplanted. Schooling was 1st to 8th grade for 123/235 (52.3 percent); monthly family income ranged from US$60 (7 percent) to more than US$400 (36 percent). Overall survival for patients with chronic myeloid leukemia, severe aplastic anemia and acute myeloid leukemia was 58, 60 and 30 percent, respectively. Thus, overall survival rates for the most frequent hematological diseases were similar to those reported in the International Registry, except for acute myeloid leukemia. This descriptive and exploratory analysis suggests the feasibility of alloBMT in a developing country like Brazil
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Enfermedades de la Médula Ósea , Trasplante de Médula Ósea , Prueba de Histocompatibilidad , Donadores Vivos , Enfermedades de la Médula Ósea , Trasplante de Médula Ósea , Brasil , Escolaridad , Estudios Retrospectivos , Factores Socioeconómicos , Tasa de SupervivenciaRESUMEN
The purpose of this study was to evaluate reticulocyte parameters by means of flow cytometric reticulocyte counting in a group of patients who had undergone autologous and allogeneic bone marrow transplantation (BMT). The pattern of reticulocyte response and the predictive value of absolute neutrophil count (ANC), platelet count, number of CD34+ cell infused and graft source for reticulocyte response were studied. We compared absolute reticulocyte count (RetAbs), mean fluorescence index (MFI) and mean reticulocyte volume/mean corpuscular volume (MRV/MCV) ratio with conventional criteria (ANC and platelet count) in 22 allogeneic and 20 autologous BMT recipients. An abrupt increase in MRV/MCV ratio or a rise in MFI value were the earliest signs of erythropoietic recovery following allogeneic transplantation (63.6 and 22.8% of cases, respectively). In 13.6% of the cases, both parameters were observed simultaneously. All but three autologous transplant recipients showed changes in reticulocyte parameters earlier than ANC recovery. Granulocyte recovery and peripheral blood progenitor cells (PBPC) graft were predictive variables for RetAbs response in allogeneic transplant recipients. In the autologous group, predictive variables for RetAbs response were a high number of CD34+ infused cells and platelet recovery. An increase in the immature reticulocyte population is the earliest sign of haematopoietic recovery following BMT.
Asunto(s)
Trasplante de Médula Ósea/normas , Supervivencia de Injerto , Reticulocitos/citología , Adolescente , Adulto , Recuento de Células Sanguíneas , Niño , Índices de Eritrocitos , Femenino , Citometría de Flujo , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Pronóstico , Recuento de Reticulocitos , Trasplante Autólogo , Trasplante HomólogoRESUMEN
Very few data are available on the comparison of infectious complications in peripheral blood stem cell transplantation (PBSCT) and bone marrow transplant (BMT). The objective of this study was to evaluate the severity and frequency of infectious complications in patients randomized to receive PBSCT or BMT. We retrospectively reviewed the charts of all patients included in a randomized clinical trial comparing PBSCT (27 patients) and BMT (29 patients). We analyzed two periods: pre-engraftment and post-engraftment. In the pre-engraftment period, we compared the two groups with respect to the duration of neutropenia, antibiotic use and hospitalization, and documentation of infection. In the post-engraftment period, we analyzed the occurrence and severity of graft-versus-host disease (GVHD), duration of cyclosporine, corticosteroids, antibiotic, antiviral and antifungal prophylaxis, number of episodes of infection, and death rates. Patients receiving PBSCT had shorter duration of neutropenia, but there were no differences in the incidence of infections or duration of antibiotic therapy. Patients receiving PBSCT had a higher incidence of extensive chronic GVHD (65% vs. 39%, P=0.08), longer duration of cyclosporine use (risk ratio [RR] 1.97), corticosteroids (RR 1.66), antibacterial (RR 2.60), antifungal (RR 2.50), anti-Pneumocystis carinii (RR 2.06) and anti-cytomegalovirus (RR 1.44) prophylaxis, and more infectious episodes (3.65 vs. 2.32 per 1000 days at risk, RR 1.57). There were no differences in death rates. Multivariate analysis identified the use of steroids as the most significant variable associated with infectious episodes. PBSCT was associated with more infections in the post-engraftment period.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Infecciones/etiología , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Adolescente , Adulto , Niño , Femenino , Enfermedad Injerto contra Huésped/etiología , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Trasplante HomólogoRESUMEN
In order to assess the effect of delaying G-CSF administration after autologous peripheral blood progenitor cell (PBPC) transplantation on the duration of neutropenia, 87 patients were randomized to receive G-CSF 5 microg/kg/day starting on day +1 (n = 45) or +5 (n = 42) following PBPC transplantation, until recovery of the neutrophils. The duration of neutropenia (<0.5 x 10(9)/l) was shorter in the day +1 group (7 vs 8 days; P = 0.02), especially in patients receiving melphalan 200 mg/m(2) and CD34(+) cell doses >3.0 x 10(6)/kg. These patients had a later onset of neutropenia after transplant. There were no differences in time to neutrophil and platelet engraftment, or in the incidence of fever and documentation of infection. Although the duration of antibiotic therapy (7 vs 10.5 days; P = 0.01) and time to hospital discharge (13 vs 15 days; P = 0.02) were shorter in the day +1 group, these differences could not be predicted by the day of G-CSF initiation in multivariate analysis. Starting G-CSF on day +1 does not result in faster neutrophil engraftment but in later onset and consequently, slightly shorter duration of neutropenia in patients who receive melphalan 200 mg/m(2) and CD34(+) cell doses >3.0 x 10(6)/kg.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Trasplante de Células Madre de Sangre Periférica/métodos , Adolescente , Adulto , Anciano , Esquema de Medicación , Femenino , Fiebre/etiología , Fiebre/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/farmacología , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Hematopoyesis/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/prevención & control , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Estudios Prospectivos , Trasplante Autólogo/efectos adversos , Trasplante Autólogo/métodos , Resultado del TratamientoRESUMEN
The purpose of the present study was to evaluate the mixed lymphocyte culture as a predictive assay of acute and chronic graft-versus-host disease (GVHD). We studied 153 patients who received a first bone marrow transplantation from human leukocyte antigen-identical siblings. Acute GVHD was observed in 26 of 128 (20.3%) patients evaluated and chronic GVHD occurred in 60 of 114 (52.6%). One-way mixed lymphocyte culture (MLC) assays were performed by the standard method. MLC results are reported as the relative response (RR) from donor against patient cells. The responses ranged from -47.0 to 40.7%, with a median of 0.5%. The Kaplan-Meier probability of developing GVHD was determined for patients with positive and negative MLC. There was no significant difference in incidence of acute GVHD between the groups studied. However, the incidence of chronic GVHD was higher in recipients with RR >4.5% than in those with RR < or =4.5%. The Cox Proportional Hazards model was used to examine the effect of MLC levels on incidence of chronic GVHD, while adjusting for the potential confounding effect of others suspected or observed risk factors. The relative risk of chronic GVHD was 2.5 for patients with positive MLC (RR >4.5%), 2.9 for those who received peripheral blood progenitor cells as a graft, and 2.2 for patients who developed previous acute GVHD. MLC was not useful for predicting acute GVHD, but MLC with RR >4.5% associated with other risk factors could predict the development of chronic GVHD, being of help for the prevention and/or treatment of this late complication.
Asunto(s)
Enfermedad Injerto contra Huésped/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Aguda , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Antígenos HLA/inmunología , Humanos , Incidencia , Prueba de Cultivo Mixto de Linfocitos/métodos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Trasplante HomólogoRESUMEN
The purpose of the present study was to evaluate the mixed lymphocyte culture as a predictive assay of acute and chronic graft-versus-host disease (GVHD). We studied 153 patients who received a first bone marrow transplantation from human leukocyte antigen-identical siblings. Acute GVHD was observed in 26 of 128 (20.3 percent) patients evaluated and chronic GVHD occurred in 60 of 114 (52.6 percent). One-way mixed lymphocyte culture (MLC) assays were performed by the standard method. MLC results are reported as the relative response (RR) from donor against patient cells. The responses ranged from -47.0 to 40.7 percent, with a median of 0.5 percent. The Kaplan-Meier probability of developing GVHD was determined for patients with positive and negative MLC. There was no significant difference in incidence of acute GVHD between the groups studied. However, the incidence of chronic GVHD was higher in recipients with RR >4.5 percent than in those with RR <=4.5 percent. The Cox Proportional Hazards model was used to examine the effect of MLC levels on incidence of chronic GVHD, while adjusting for the potential confounding effect of others suspected or observed risk factors. The relative risk of chronic GVHD was 2.5 for patients with positive MLC (RR >4.5 percent), 2.9 for those who received peripheral blood progenitor cells as a graft, and 2.2 for patients who developed previous acute GVHD. MLC was not useful for predicting acute GVHD, but MLC with RR >4.5 percent associated with other risk factors could predict the development of chronic GVHD, being of help for the prevention and/or treatment of this late complication
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Enfermedad Aguda , Brasil , Enfermedad Crónica , Enfermedad Injerto contra Huésped , Antígenos HLA , Incidencia , Prueba de Cultivo Mixto de Linfocitos , Valor Predictivo de las Pruebas , Factores de Riesgo , Trasplante HomólogoRESUMEN
Trials have demonstrated that high-dose escalation followed by autologous transplantation can promote better long-term survival as salvage treatment in malignant lymphomas. The aim of the present nonrandomized clinical trial was to demonstrate the role of high-dose cyclophosphamide (HDCY) in reducing tumor burden and also to determine the effectiveness of HDCY followed by etoposide (VP-16) and methotrexate (MTX) in Hodgkin's disease plus high-dose therapy with peripheral blood progenitor cell (PBPC) transplantation as salvage treatment. From 1998 to 2000, 33 patients with a median age of 33 years (13-65) affected by aggressive non-Hodgkin's lymphoma (NHL) (60.6 percent) or persistent or relapsed Hodgkin's disease (39.4 percent) were enrolled and treated using high dose escalation (HDCY + HDVP-16 plus HDMTX in Hodgkin's disease) followed by autologous PBPC transplantation. On an "intention to treat" basis, 33 patients with malignant lymphomas were evaluated. The overall median follow-up was 400 days (40-1233). Thirty-one patients underwent autografting and received a median of 6.19 x 10(6)/kg (1.07-29.3) CD34+ cells. Patients who were chemosensitive to HDCY (N = 22) and patients who were chemoresistant (N = 11) presented an overall survival of 96 and 15 percent, respectively (P<0.0001). Overall survival was 92 percent for chemosensitive patients and 0 percent for patients who were still chemoresistant before transplantation (P<0.0001). Toxicity-related mortality was 12 percent (four patients), related to HDCY in two cases and to transplant in the other two. HDCY + HDVP-16 plus HDMTX in only Hodgkin's disease followed by autologous PBPC proved to be effective and safe as salvage treatment for chemosensitive patients affected by aggressive NHL and Hodgkin's disease, with acceptable mortality rates related to sequential treatment
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Enfermedad de Hodgkin/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/química , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Terapia Recuperativa , Ciclofosfamida , Estudios de Seguimiento , Trasplante AutólogoRESUMEN
Trials have demonstrated that high-dose escalation followed by autologous transplantation can promote better long-term survival as salvage treatment in malignant lymphomas. The aim of the present nonrandomized clinical trial was to demonstrate the role of high-dose cyclophosphamide (HDCY) in reducing tumor burden and also to determine the effectiveness of HDCY followed by etoposide (VP-16) and methotrexate (MTX) in Hodgkin's disease plus high-dose therapy with peripheral blood progenitor cell (PBPC) transplantation as salvage treatment. From 1998 to 2000, 33 patients with a median age of 33 years (13-65) affected by aggressive non-Hodgkin's lymphoma (NHL) (60.6%) or persistent or relapsed Hodgkin's disease (39.4%) were enrolled and treated using high dose escalation (HDCY + HDVP-16 plus HDMTX in Hodgkin's disease) followed by autologous PBPC transplantation. On an "intention to treat" basis, 33 patients with malignant lymphomas were evaluated. The overall median follow-up was 400 days (40-1233). Thirty-one patients underwent autografting and received a median of 6.19 x 10(6)/kg (1.07-29.3) CD34+ cells. Patients who were chemosensitive to HDCY (N = 22) and patients who were chemoresistant (N = 11) presented an overall survival of 96 and 15%, respectively (P<0.0001). Overall survival was 92% for chemosensitive patients and 0% for patients who were still chemoresistant before transplantation (P<0.0001). Toxicity-related mortality was 12% (four patients), related to HDCY in two cases and to transplant in the other two. HDCY + HDVP-16 plus HDMTX in only Hodgkin's disease followed by autologous PBPC proved to be effective and safe as salvage treatment for chemosensitive patients affected by aggressive NHL and Hodgkin's disease, with acceptable mortality rates related to sequential treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Terapia Recuperativa , Adolescente , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Trasplante AutólogoRESUMEN
CONTEXT: Young patients affected by acute myeloid leukemia (AML) achieve complete remission (CR) using conventional chemotherapy in about 55-85%. However, 30% of patients fail to achieve CR and the remission duration is often only about 12 months. More intensive treatment after CR seems to be necessary in order to maintain CR and obtain a definitive cure. In Brazil, few reports have been published on this important subject. OBJECTIVE: The aim of this study was to describe a Brazilian experience in the treatment of "de novo" acute myeloid leukemia (AML) in younger adult patients (age < 60 years). DESIGN: Retrospective analysis. SETTING: University Hospital, Hematology and Hemotherapy Center, State University of Campinas, Brazil. PARTICIPANTS: Newly diagnosed cases of "de novo" AML in the period from January 1994 to December 1998 were evaluated retrospectively, in relation to response to treatment, overall survival (OS) and disease free survival (DFS). Cases with acute promyelocytic leukemia (APL) were also included in this analysis. RESULTS: On the basis of an intention to treat, 78 cases of AML, including 17 cases of APL, were evaluated. The overall median follow-up was 272 days. The complete remission (CR) rate was 63.6% in the AML group (excluding APL) and 78% in the APL group. The 5-year estimated disease-free survival (DFS) was 80% for the APL group and 34% for the AML group (P = 0.02). The 5-year estimated overall survival (OS) was 52% for the APL group and 20.5% for the AML group, respectively (P = NS). Relapse was observed in 12/39 (30.7%) patients with AML and 1/11 (9%) with APL. CONCLUSIONS: These results are similar to those reported in the literature. However, relapse and mortality rates remain high, and a search for more aggressive strategies in order to prevent relapse is recommended.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Trasplante de Médula Ósea , Brasil , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mieloide/terapia , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/terapia , Masculino , Persona de Mediana Edad , Inducción de Remisión/métodos , Estudios Retrospectivos , Estadísticas no Paramétricas , Tasa de SupervivenciaRESUMEN
OBJECTIVE: We analysed peripheral blood progenitor cell (PBPC) mobilisation and collection in order to assess the main factors related to CD34(+) cell yields in patients affected by haematological malignancies. PATIENTS AND METHODS: The features of CD34(+) cell mobilisation of patients with haematological malignancies that underwent autologous bone marrow transplantation were examined. Mobilisation chemotherapy consisted mainly of cyclophosphamide (CY) 4 or 7 g/m(2) followed by growth factors. Leukapheresis was started when the WBC counts reached 1.0x10(9)/l with the aim to collect at least 5x10(6) CD34(+) cells/kg body weight. The aphereses were performed on continuous-flow blood cell separators. The analysed variables were: age, diagnosis, CT mobilisation regimen, type of growth factor, number of previous CT lines, prior radiotherapy, days for WBC recovery and number of aphereses procedures to achieve the target of CD34(+) cells. RESULTS: There were 41 consecutive patients (26 M/15 F): 21 non-Hodgkin's lymphoma (NHL), 15 Hodgkin's disease (HD), two chronic myeloid leukaemia (CML) and three multiple myeloma (MM). Eleven patients could not collect the proposed threshold of CD34(+) cells. CY 4 mobilised patients recovered WBC counts in less days (P=0.03). By ANOVA, the days to WBC recovery had a linear function of the predictors "number of aphereses" and "type of mobilisation CT" (coefficients: 0.86 and 0.95, respectively). For the number of aphereses and WBC recovery after CT mobilisation, we obtained a correlation coefficient of 0.36 (P=0.02). CONCLUSION: This study shows that it is feasible to mobilise and collect PBPC in patients previously treated with CT with or without RT. There was a linear correlation between the days for WBC recovery and the number of aphereses needed to collect the target number of CD34(+) cells. The study suggests that early WBC recovery, using mainly CY 4 mobilisation chemotherapy, is an important predictor of a low number of aphereses to achieve a good CD34(+) yield.
Asunto(s)
Recuento de Células Sanguíneas , Neoplasias Hematológicas/sangre , Movilización de Célula Madre Hematopoyética , Leucaféresis , Adolescente , Adulto , Antígenos CD34/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Caspasa 14 , Caspasas/administración & dosificación , Niño , Cisplatino/administración & dosificación , Terapia Combinada , Ciclofosfamida/farmacología , Citarabina/administración & dosificación , Dexametasona/administración & dosificación , Etopósido/administración & dosificación , Estudios de Factibilidad , Femenino , Factor Estimulante de Colonias de Granulocitos/farmacología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/terapia , Células Madre Hematopoyéticas , Humanos , Control de Infecciones , Recuento de Leucocitos , Leucocitos Mononucleares , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/farmacología , Factores de TiempoRESUMEN
Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75. 9%) affected by aggressive and 7 (24.1%) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0. 04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.
Asunto(s)
Amifostina/farmacología , Antineoplásicos Alquilantes/administración & dosificación , Ciclofosfamida/administración & dosificación , Citoprotección , Linfoma no Hodgkin/tratamiento farmacológico , Protectores contra Radiación/uso terapéutico , Adolescente , Adulto , Amifostina/efectos adversos , Antineoplásicos Alquilantes/efectos adversos , Ciclofosfamida/efectos adversos , Citoprotección/efectos de los fármacos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protectores contra Radiación/efectos adversos , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
Clinical trials indicate that amifostine may confer protection on various normal tissues without attenuating anti-tumor response. When administered prior to chemotherapy or radiotherapy, it may provide a broad spectrum of cytoprotection including against alkylating drugs. The mechanism of protection resides in the metabolism at normal tissue site by membrane-bound alkaline phosphatase. Toxicity of this drug is moderate with hypotension, nausea and vomiting, and hypocalcemia being observed. We report a phase II study using amifostine as a protective drug against high-dose cyclophosphamide (HDCY) (7 g/m2), used to mobilize peripheral blood progenitor cells (PBPC) and to reduce tumor burden. We enrolled 29 patients, 22 (75.9 percent) affected by aggressive and 7 (24.1 percent) by indolent non-Hodgkin's lymphoma (NHL), who were submitted to 58 infusions of amifostine and compared them with a historical group (33 patients) affected by aggressive NHL and treated with VACOP-B followed by HDCY. The most important results in favor of amifostine were the reduction of intensity of cardiac, pulmonary and hepatic toxicity, and a significant reduction of frequency and severity of mucositis (P = 0.04). None of the 29 patients died in the protected group, while in the historical group 2/33 patients died because of cardiac or pulmonary toxicity and 2 patients stopped therapy due to toxicity. Amifostine did not prevent the aplastic phase following HDCY. PBPC collection and hematological recovery were adequate in both groups. The number of CFU-GM (colony-forming units-granulocyte/macrophage) colonies and mononuclear cells in the apheresis products was significantly higher in the amifostine group (P = 0.02 and 0.01, respectively). Side effects were mild and easily controlled. We conclude that amifostine protection should be useful in HDCY to protect normal tissues, with acceptable side effects.