RESUMEN
Genetic abnormalities are critical prognostic factors for patients diagnosed with multiple myeloma (MM). This retrospective, multicenter study aimed to contribute with the genetic and clinical characterization of MM patients in a country with continental dimensions such as Brazil. Genetic abnormalities were assessed by cIg-fluorescent in situ hybridization (cIg-FISH) in a series of 152 MM patients (median age 55 years, 58.5% men). Overall, genetic abnormalities were detected in 52.7% (80/152) of patients. A 14q32 rearrangement was detected in 33.5% (n=51), including t(11;14), t(4;14) and t(14;16) in 18.4, 14.1, and 1% of cases, respectively. del(13q) was identified in 42.7% (n=65) of patients, of whom 49.2% (32/65) presented a concomitant 14q32 rearrangement. del(17p) had a frequency of 5.2% (n=8). del(13q) was associated with high plasma cell burden (≥50%, P=0.02), and del(17p) with advanced ISS stages (P=0.05) and extramedullary disease (P=0.03). t(4;14) was associated with advanced Durie-Salmon stages (P=0.008), renal insufficiency (P=0.01) and was more common in patients over 60 years old. This study reports similar frequencies of genetic abnormalities to most series worldwide, whereas the t(14;16) and del(17p), two high risk factors for newly diagnosed patients, exhibited lower frequencies. Our results expand the knowledge on the molecular features of MM in Brazil, a country where innovative therapies that could overcome a poor prognosis for some genetic abnormalities are not always available.
Asunto(s)
Aberraciones Cromosómicas , Hibridación Fluorescente in Situ/métodos , Mieloma Múltiple/genética , Células Plasmáticas/patología , Adulto , Anciano , Análisis Citogenético , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Sondas de Oligonucleótidos/genética , Pronóstico , Estudios RetrospectivosRESUMEN
The introduction of agents such as thalidomide, lenalidomide, and bortezomib has changed the management of patients with multiple myeloma who are not eligible for autologous transplantation, many of whom are elderly. We sought to compare three thalidomide-based oral regimens among such patients in Latin America. We randomized patients with newly diagnosed multiple myeloma with measurable disease to one of the following regimens: melphalan, prednisone, and thalidomide (MPT); cyclophosphamide, thalidomide, and dexamethasone (CTD); and thalidomide and dexamethasone (TD). The TD arm was closed prematurely and was analyzed only descriptively. The primary endpoint was the overall response rate (ORR), whereas progression-free survival (PFS) and overall survival (OS) were secondary endpoints. The accrual rate was slower than expected, and the study was terminated after 82 patients had been randomized. The ORRs were 67.9 % with MPT, 89.7 % with CTD, and 68.7 % with TD (p = 0.056 for the comparison between MPT and CTD). The median PFS was 24.1 months for MPT, 25.9 months for CTD, and 21.5 months for TD. There were no statistically significant differences in PFS or OS between MPT and CTD. In an unplanned logistic regression analysis, ORR was significantly associated with treatment with CTD (p = 0.046) and with performance status of 0 or 1 (p = 0.035). Based on the current results, no definitive recommendations can be made regarding the comparative merit of the regimens tested. Nevertheless and until the results of further studies become available, we recommend either CTD or MPT as suitable frontline regimens for patients with multiple myeloma who are not candidates to transplantation in settings where lenalidomide and bortezomib are not available.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Talidomida/administración & dosificación , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Trasplante AutólogoRESUMEN
Genetic abnormalities are critical prognostic factors for patients diagnosed with multiple myeloma (MM). This retrospective, multicenter study aimed to contribute with the genetic and clinical characterization of MM patients in a country with continental dimensions such as Brazil. Genetic abnormalities were assessed by cIg-fluorescent in situ hybridization (cIg-FISH) in a series of 152 MM patients (median age 55 years, 58.5% men). Overall, genetic abnormalities were detected in 52.7% (80/152) of patients. A 14q32 rearrangement was detected in 33.5% (n=51), including t(11;14), t(4;14) and t(14;16) in 18.4, 14.1, and 1% of cases, respectively. del(13q) was identified in 42.7% (n=65) of patients, of whom 49.2% (32/65) presented a concomitant 14q32 rearrangement. del(17p) had a frequency of 5.2% (n=8). del(13q) was associated with high plasma cell burden (≥50%, P=0.02), and del(17p) with advanced ISS stages (P=0.05) and extramedullary disease (P=0.03). t(4;14) was associated with advanced Durie-Salmon stages (P=0.008), renal insufficiency (P=0.01) and was more common in patients over 60 years old. This study reports similar frequencies of genetic abnormalities to most series worldwide, whereas the t(14;16) and del(17p), two high risk factors for newly diagnosed patients, exhibited lower frequencies. Our results expand the knowledge on the molecular features of MM in Brazil, a country where innovative therapies that could overcome a poor prognosis for some genetic abnormalities are not always available.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Aberraciones Cromosómicas , Hibridación Fluorescente in Situ/métodos , Mieloma Múltiple/genética , Células Plasmáticas/patología , Análisis Citogenético , Citometría de Flujo , Sondas de Oligonucleótidos/genética , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: The epidemiology of and risk factors for invasive mold disease (IMD) among allogeneic hematopoietic cell transplant (HCT) recipients may vary according to the region. In this study, we sought to evaluate risk factors for IMD in our patient population. METHODS: Between May 2007 and July 2009, all HCT recipients from 8 Brazilian centers were followed prospectively until 1 year post transplant. Cases of IMD were classified as early (before day +40) or late (after day +40). Patients with IMD (cases) were compared with controls (patients without IMD) using univariate and multivariate Cox regression analysis. RESULTS: Among 345 HCT recipients, 28 IMDs were diagnosed. Risk factors for early IMD were acute myeloid leukemia (hazard ratio [HR] 2.95, 95% confidence interval [95% CI] 1.13-7.68, P = 0.03) and transplant with a human leukocyte antigen-mismatched donor (HR 3.38, 95% CI 1.18-9.68, P = 0.02), and for late IMD risk factors were lymphoma (HR 8.49, 95% CI 2.35-30.68, P = 0.001), cytomegalovirus reactivation (HR 5.51, 95% CI 1.15-26.47, P = 0.03), and neutropenia (HR 3.49, 95% CI 1.01-12.13, P = 0.049). CONCLUSION: The variables identified in this study may help to define risk groups, and to tailor special preventive measures to patients at higher risk to develop IMD.
Asunto(s)
Citomegalovirus/fisiología , Antígenos HLA/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/complicaciones , Micosis/prevención & control , Adolescente , Adulto , Brasil , Niño , Preescolar , Intervalos de Confianza , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Neutropenia/complicaciones , Factores de Riesgo , Receptores de Trasplantes , Trasplante Homólogo/efectos adversos , Activación Viral , Adulto JovenRESUMEN
The epidemiology of bacteremia developing during neutropenia has changed in the past decade, with the re-emergence of Gram-negative (GN) bacteria and the development of multidrug resistance (MDR) among GN bacteria. We conducted a case-control study in order to identify factors associated with bacteremia due to multidrug-resistant Gram-negative (MDRGN) isolates in hematopoietic stem cell transplant recipients. Ten patients with MDRGN bacteremia were compared with 44 patients with GN bacteremia without MDR. Bacteremia due to Burkholderia or Stenotrophomonas sp was excluded from analysis (3 cases), because the possibility of intrinsical resistance. Infection due to MDRGN bacteria occurred in 2.9% of 342 hematopoietic stem cell transplant recipients. Klebsiella pneumoniae was the most frequent MDRGN (4 isolates), followed by Pseudomonas aeruginosa (3 isolates). Among non-MDRGN, P. aeruginosa was the most frequent agent (34%), followed by Escherichia coli (30%). The development of GN bacteremia during the empirical treatment of febrile neutropenia (breakthrough bacteremia) was associated with MDR (P < 0.001, odds ratio = 32, 95% confidence interval = 5_190) by multivariate analysis. Bacteremia due to MDRGN bacteria was associated with a higher death rate by univariate analysis (40 vs 9%; P = 0.03). We were unable to identify risk factors on admission or at the time of the first fever, but the occurrence of breakthrough bacteremia was strongly associated with MDRGN bacteria. An immediate change in the antibiotic regimen in such circumstances may improve the prognosis of these patients.
Asunto(s)
Bacteriemia/microbiología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas/microbiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neutropenia/microbiología , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Estudios de Casos y Controles , Niño , Femenino , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
The epidemiology of bacteremia developing during neutropenia has changed in the past decade, with the re-emergence of Gram-negative (GN) bacteria and the development of multidrug resistance (MDR) among GN bacteria. We conducted a case-control study in order to identify factors associated with bacteremia due to multidrug-resistant Gram-negative (MDRGN) isolates in hematopoietic stem cell transplant recipients. Ten patients with MDRGN bacteremia were compared with 44 patients with GN bacteremia without MDR. Bacteremia due to Burkholderia or Stenotrophomonas sp was excluded from analysis (3 cases), because the possibility of intrinsical resistance. Infection due to MDRGN bacteria occurred in 2.9 percent of 342 hematopoietic stem cell transplant recipients. Klebsiella pneumoniae was the most frequent MDRGN (4 isolates), followed by Pseudomonas aeruginosa (3 isolates). Among non-MDRGN, P. aeruginosa was the most frequent agent (34 percent), followed by Escherichia coli (30 percent). The development of GN bacteremia during the empirical treatment of febrile neutropenia (breakthrough bacteremia) was associated with MDR (P < 0.001, odds ratio = 32, 95 percent confidence interval = 5_190) by multivariate analysis. Bacteremia due to MDRGN bacteria was associated with a higher death rate by univariate analysis (40 vs 9 percent; P = 0.03). We were unable to identify risk factors on admission or at the time of the first fever, but the occurrence of breakthrough bacteremia was strongly associated with MDRGN bacteria. An immediate change in the antibiotic regimen in such circumstances may improve the prognosis of these patients.
Asunto(s)
Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Bacteriemia/microbiología , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas/microbiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neutropenia/microbiología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Estudios de Casos y Controles , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
The incidence of Gram-negative bacteremia has increased in hematopoietic stem cell transplant (HSCT) recipients. We prospectively collected data from 13 Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring early post transplant, and to identify factors associated with infection due to multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate with resistance to at least two of the following: third- or fourth-generation cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram-positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram-negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and 37% were MDR. These isolates were recovered from 20 patients, representing 5% of all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis, treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95% confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47, 95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative isolates. These findings may have important clinical implications in the decision of giving prophylaxis and selecting the empiric antibiotic regimen.
Asunto(s)
Bacteriemia/mortalidad , Resistencia a Múltiples Medicamentos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/mortalidad , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Antibacterianos/uso terapéutico , Brasil/epidemiología , Carbapenémicos/uso terapéutico , Cefalosporinas/uso terapéutico , Niño , Preescolar , Femenino , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Neutropenia/epidemiología , Ácido Penicilánico/análogos & derivados , Ácido Penicilánico/uso terapéutico , Piperacilina/uso terapéutico , Combinación Piperacilina y Tazobactam , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de RiesgoRESUMEN
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
Engraftment syndrome (ES) is an increasingly reported complication of hematopoietic stem cell transplantation (HSCT). In order to better characterize the clinical criteria for the diagnosis of ES, we retrospectively analyzed 125 autologous HSCT recipients. ES was first defined as the presence of noninfectious fever plus skin rash. Patients with and without these findings were compared (univariate and multivariate analyses) regarding the presence of weight gain, hypoalbuminemia, pulmonary infiltrates, diarrhea, neurological manifestations and jaundice. The variables that are significantly more frequent in patients with fever and skin rash were incorporated in the definition criteria. The final diagnostic criteria were noninfectious fever plus any of the following: skin rash, pulmonary infiltrates or diarrhea. The incidence of ES was 20%. The single risk factor for ES by multivariate analysis was a diagnosis other than Hodgkin's disease (odds ratio 6.17, 95% confidence interval 1.38-27.78). Patients with ES received empirical antifungal therapy more frequently than patients without the syndrome (40 vs 19%, P=0.03), and had a longer duration of hospitalization (P=0.0007). The prospective application of these diagnostic criteria may have a favorable impact on the early diagnosis of the syndrome, with the initiation of corticosteroids and a reduction in the unnecessary use of antimicrobial agents.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Anciano , Niño , Exantema/etiología , Femenino , Fiebre/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Síndrome , Trasplante AutólogoRESUMEN
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
A prospective randomized trial was performed to compare teicoplanin to vancomycin as part of the empirical antibiotic therapy of febrile neutropenic cancer patients. Fifty-three patients were randomized to receive ceftazidime (100 mg/kg daily every 8 h), amikacin (15 mg/kg daily every 8 h) and teicoplanin (6 mg/kg once a day) and 53 other patients received ceftazidime, amikacin (same dosages) and vancomycin (30 mg/kg/day every 6 h). In 99 evaluable episodes, the success rates were 54% for patients receiving teicoplanin and 52% for patients receiving vancomycin (p=0.76, 95% CI-18-23). The response rates were similar for patients with unexplained fever and for patients with documented infections. There were no differences in renal toxicity or cutaneous side effects between the two groups. The overall death rate was 18.9%, with 10 deaths in each group. The most important factor associated with death was the diagnosis of a fungal infection (p=0.001). Teicoplanin seems to be well tolerated and as effective as vancomycin in the empirical antibiotic therapy of fever in neutropenic cancer patients.
Asunto(s)
Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Ceftazidima/uso terapéutico , Quimioterapia Combinada/uso terapéutico , Fiebre , Leucemia/complicaciones , Linfoma/complicaciones , Neutropenia , Teicoplanina/uso terapéutico , Vancomicina/uso terapéutico , Adolescente , Adulto , Anciano , Infecciones Bacterianas/complicaciones , Trasplante de Médula Ósea , Niño , Femenino , Infecciones por Bacterias Gramnegativas/complicaciones , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Leucemia/terapia , Linfoma/terapia , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The role of bone marrow biopsy in the staging of Hodgkin's disease is undergoing reevaluation. We have studied the relationship of clinical factors to the presence of bone marrow involvement in 130 previously untreated patients with Hodgkin's disease. The presence of fever, spleen enlargement, anemia, leukopenia, poor performance status and poor histologic subgroups were positively correlated with the presence of bone marrow involvement in the univariate analysis. In the multivariate analysis, only fever, spleen involvement, leukopenia and poor histologic subgroups were significant. The predictive value of the absence of fever in regard to the absence of bone marrow involvement was 98%. The likelihood of bone marrow involvement in the absence of all four significant factors was only 0.05%. Patients without these clinical factors should probably not be submitted to a bone marrow biopsy as part of the staging procedures performed in Hodgkin's disease.
Asunto(s)
Enfermedades de la Médula Ósea/diagnóstico , Enfermedad de Hodgkin/complicaciones , Adolescente , Adulto , Anciano , Enfermedades de la Médula Ósea/etiología , Brasil , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Estados Unidos , Salud UrbanaRESUMEN
Skin nodules can be the first evidence of a disseminated fungal infection in febrile neutropenic patients. We present our experience in the diagnosis of this clinical problem in five patients treated for serious hematologic conditions in our Service. There were two cases of Candida sp., two of Fusarium sp., and one of Trichosporon sp.. The immediate assessment of any suspicious lesion, including a biopsy of the lesion for microbiological and histopathologic examinations, will usually lead to the correct diagnosis.