RESUMO
OBJECTIVES: To demonstrate the bioequivalence between 2 intravenous immunoglobulin (IVIG) preparations, TEGELINE® and ClairYg®, a ready-to-use 5% IVIG, in primary immunodeficiency (PID). Secondary objectives were to assess the efficacy, safety and pharmacokinetics of ClairYg®. METHODS: Twenty-two adult PID patients receiving stable doses of TEGELINE® (5% lyophilized IVIG) were switched to ClairYg® for 6 months. ClairYg® was administered under the same conditions as TEGELINE®, either every 3 or 4 weeks. The primary endpoint was mean average total IgG trough level at steady state with ClairYg® versus TEGELINE®. Clinical efficacy was also assessed in terms of infections and associated events. RESULTS: Bioequivalence was established with a mean average total IgG trough level at steady state being 8.05g/L with TEGELINE® and 9.17g/L with ClairYg® (i.e. geometric mean for the difference between ClairYg® and TEGELINE® was 1.136; [90% CI: 1.092-1.181] P<0.001), within the pre-specified margin to establish bioequivalence (0.80-1.25). Total IgG trough levels remained clinically adequate (>4-6g/L) throughout the study. No patient was hospitalized for infection or had serious bacterial infections while receiving ClairYg®. The median annualized infections rate per patient was similar for both products: 4.35 [0; 21.8] for TEGELINE® and 4.30 [0; 15.1] for ClairYg®. Infections were less common with higher IgG trough levels (>8.16g/L). ClairYg® showed good safety, in particular good hepatic and renal tolerance, and did not induce hemolysis. ClairYg® pharmacokinetics profile was comparable to that of TEGELINE®. CONCLUSION: ClairYg® is safe and effective in the treatment of adult PID.
Assuntos
Imunoglobulinas Intravenosas/farmacocinética , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/terapia , Adulto , Feminino , França/epidemiologia , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina G/uso terapêutico , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/metabolismo , Imunoterapia/métodos , Masculino , Pessoa de Meia-Idade , Equivalência Terapêutica , Resultado do Tratamento , Adulto JovemRESUMO
Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.
Assuntos
Deleção Cromossômica , Análise Citogenética , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Benzamidas , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 4/genética , Éxons , Feminino , França , Humanos , Síndrome Hipereosinofílica/tratamento farmacológico , Mesilato de Imatinib , Hibridização in Situ Fluorescente/métodos , Interleucina-5/sangue , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Análise de Sequência de DNA , Serina Endopeptidases/sangue , TriptasesRESUMO
With the introduction of new drugs such as alpha-interferon (IFN) and purine analogs, the management of hairy cell leukemia (HCL) patients has changed. However, deoxycoformycin (DCF) produced higher complete remission rates than IFN. The current study was undertaken to provide long-term data on duration of overall survival (OS) and disease-free survival (DFS) and incidence of subsequent malignancies. We retrospectively analyzed the data of patients treated with DCF (4 mg/m2/day, every 2 weeks) from 39 French centers. In 84 of 238 included patients, DCF was the first-line therapy. Pretreatment variables influencing the achievement of complete remission, DFS, and OS were identified by multivariate analysis. Two hundred and thirty-eight patients received a median of nine cycles (range, 1-19 cycles). A complete remission was obtained in 182 of 230 evaluable patients (79%) and a partial response was obtained in 38 patients, for an overall response rate of 95.6%. In the multivariate analysis hemoglobin level less than 100 g/l and leukocytes less than 2 x 10(9)/l were parameters adversely influencing complete remission achievement. With a median follow-up of 63.5 months (range, 0.39-138.4 months), disease recurrence was observed in 34 of 220 responding patients (15%). The estimated 5-years and 10-years DFS was 88.1% and 68.8%, respectively. Hemoglobin level less than 100 g/l and leukocytes less than 2 x 10(9)/l were the pre-treatment variables associated with a shorter DFS. The estimated 5-year and 10-year OS were 89.4% and 88.7%, respectively. Hemoglobin level less than 100 g/l, leukocytes less than 2 x 10(9)/l, and adenopathy were significant factors of reduced survival. Hematologic toxicity was the main side-effect, followed by infection and emesis. During the period of follow-up, 18 patients developed second cancer, but the standardized incidence ratio was 0.95. Pentostatin is a highly effective regimen for hairy cell leukemia that produces durable complete responses. Toxicity of DCF is acceptable. Subsequent malignancies do not appear to be increased with pentostatin treatment.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Pentostatina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , França/epidemiologia , Humanos , Leucemia de Células Pilosas/epidemiologia , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Segunda Neoplasia Primária , Pentostatina/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Treatment combining ATRA and chemotherapy (CT) has improved the outcome of APL patients, by comparison with CT alone. ATRA syndrome is a life-threatening complication of ATRA treatment whose prophylaxis remains somewhat controversial. In APL93 trial, newly diagnosed APL patients =65 years and with initial WBC counts below 5000/mm(3) were randomized between ATRA until CR achievement followed by CT (ATRA --> CT) and ATRA with early addition of CT, on day 3 of ATRA treatment (ATRA + CT). The incidence of ATRA syndrome in the ATRA --> CT arm was 18% (22/122) as compared to 9.2% (17/184) in the ATRA + CT arm (P = 0.035). In the ATRA --> CT arm, three (2.5%) patients died from ATRA syndrome, as compared to one (0.5%) in the ATRA + CT group. Early addition of chemotherapy to ATRA in newly diagnosed APL with low WBC counts significantly reduced the incidence of ATRA syndrome.
Assuntos
Leucemia Promielocítica Aguda/tratamento farmacológico , Leucopenia/tratamento farmacológico , Tretinoína/efeitos adversos , Tretinoína/uso terapêutico , Adulto , Idade de Início , Antineoplásicos/uso terapêutico , Feminino , Humanos , Leucemia Promielocítica Aguda/sangue , Contagem de Leucócitos , Leucopenia/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome , Resultado do TratamentoRESUMO
Idiopathic hypereosinophilic syndrome is characterised by chronic hypereosinophilia leading to tissue damage, and after exclusion of reactive eosinophilia. Until recently no specific or efficient therapeutic was available. In 2003, a recurrent interstitial deletion 4q12 leading to the fusion of the FIP1L1 and PDGFRA genes was detected in hypereosinophilic syndromes. The resulting protein has constitutive tyrosine kinase activity which explains clinical and cytological remission of hypereosinophilic syndrome after treatment by a specific tyrosine kinase inhibitor, imatinib mesylate or Glivec, usually used in chronic myeloid leukaemia. Here we report a patient with hypereosinophilic syndrome associated to peculiar morphology of neutrophilic series and the 4q12 deletion. He presented clinical and haematological remission since the introduction of imatinib mesylate therapy.
Assuntos
Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/patologia , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Benzamidas , Humanos , Síndrome Hipereosinofílica/etiologia , Síndrome Hipereosinofílica/genética , Mesilato de Imatinib , MasculinoRESUMO
Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density.
Assuntos
Gamopatia Monoclonal de Significância Indeterminada/complicações , Fraturas da Coluna Vertebral/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Análise Multivariada , Prevalência , Estudos Prospectivos , Radiografia , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/epidemiologiaRESUMO
This prospective phase II study was undertaken to evaluate the efficacy and toxicity of early intensive therapy followed by purged autologous bone marrow transplantation (ABMT) in patients with follicular lymphoma with high tumor burden. All patients received the VCAP regimen (vindesine, cyclophosphamide, doxorubicin and prednisone) as conventional chemotherapy and DHAP as second-line therapy. Twenty-nine consecutive patients were included in the study. Twenty-seven patients were grafted, seven in first complete remission (CR) and 20 in first partial remission (PR). Preparative therapy consisted of cyclophosphamide and total body irradiation (TBI) in all the patients. With a median follow-up of 6 years, the actuarial overall survival is 64% and the actuarial event-free survival is 55%. Two treatment-related early deaths were observed. Eleven patients were informative for serial PCR analysis of minimal residual disease after ABMT: two relapsed, four remained disease-free with PCR positivity and five were disease-free with PCR negativity. These encouraging results lay the basis of future prospective randomized trials comparing autologous stem cell transplantation as front-line treatment with conventional chemotherapy for patients with bad prognostic factors.
Assuntos
Purging da Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Linfoma Folicular/terapia , Linfoma não Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Genes de Imunoglobulinas , Genes bcl-2 , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Doenças Pulmonares Intersticiais/etiologia , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/genética , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Neutropenia/etiologia , Reação em Cadeia da Polimerase , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Recidiva , Indução de Remissão , Sepse/etiologia , Análise de Sobrevida , Trombocitopenia/etiologia , Translocação Genética , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
Chronic lymphocytic leukaemia is the most frequent haematological cancer in adult patients, and its incidence raises with aging. Diagnosis needs several clinical and biological data, but hemogram together with the morphological and immunophenotypic analysis of the lymphoid cells take the major place. If the diagnosis is performed easily in about 65% of the patients, various clinicobiological entities were reported in the past few years that must be identified, at least because some are of adverse prognosis. Moreover, the other chronic lymphoid neoplasms, corresponding to the various low and intermediate grade non-Hodgkin's lymphomas (mainly of follicular type, marginal zone, mantle cell zone), may disseminate within the blood and the bone marrow. Those circulating lymphoma cells must be identified at diagnosis in order to perform the accurate diagnosis and to avoid an erroneous diagnosis of atypical chronic lymphocytic leukaemia. Up to 90% of lymphoid malignancies are B cell disorders, contrasting with only a few cases of T cell origin: some of those latter cases cannot be neglected however, as they may be observed in Western countries. Most recent classifications (REAL and WHO) defined all hematological malignancies: each entity referred to clinical, morphological, immunological, cytogenetic, and molecular findings. The basis of these classifications is pathophysiological, trying in each disorder to define a normal counterpart to the pathological clone. Reviewing main steps of the immune response in the normal patient, corresponding to those involving B cells, it is possible indeed to localize and demonstrate a function for many of the cells that expand in lymphoid malignancies.
Assuntos
Neoplasias Hematológicas/fisiopatologia , Leucemia Linfocítica Crônica de Células B/fisiopatologia , Linfoma não Hodgkin/fisiopatologia , Adulto , Doença Crônica , Neoplasias Hematológicas/classificação , Neoplasias Hematológicas/patologia , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/epidemiologia , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/patologiaRESUMO
PURPOSE: Among neutropenic patients, diagnosis of invasive pulmonary aspergillosis is difficult. Computed tomographic scan, bronchoalveolar lavage and histology are considered invasive procedures, because they represent an infectious risk for these immunocompromised patients. METHODS: We describe the clinical and noninvasive paraclinical (X-rays, serology) signs of invasive pulmonary aspergillosis, from a retrospective study of 16 cases in a haematology unit. RESULTS: Outside of fever and chills, cough and polypnea are the earliest signs, followed by chest pain, dyspnea, lung auscultation changes, and haemoptysis. The sensitivity of each sign is higher than 56%. Before the onset of lung auscultation changes, the chest X-ray shows mainly unilateral alveolar infiltrates. Sensitivity of serology is weak (25%), but contributed to early diagnosis in 16.6% of cases. CONCLUSION: A better knowledge of the invasive pulmonary aspergillosis clinical, radiological and serological signs could help the practician to prescribe an 'invasive' investigation (computed tomographic scan, bronchoalveolar lavage) to confirm the diagnosis of this fungal infection.
Assuntos
Aspergilose/diagnóstico , Leucemia/complicações , Pneumopatias Fúngicas/diagnóstico , Aspergilose/diagnóstico por imagem , Auscultação , Líquido da Lavagem Broncoalveolar , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Pneumopatias Fúngicas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Prognóstico , Radiografia Torácica , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
Imatinib mesylate is the sole BCR-ABL tyrosine kinase inhibitor approved as first-line treatment of accelerated-phase (AP) chronic myeloid leukemia (CML). Indication was based on the STI571 0109 study, in which imatinib favorably compared to historical treatments in patients failing prior therapies. The relevance of these results to currently newly diagnosed AP-CML patients remains unknown. We evaluated the benefit of imatinib in 42 newly diagnosed AP-CML patients. In all, 16 patients had hematological acceleration without chromosomal abnormalities in addition to the Philadelphia chromosome (ACAs; HEM-AP), 16 solely had ACAs (ACA-AP) and 10 had hematological acceleration plus ACAs (HEM-AP + ACA). Major cytogenetic responses were achieved in 93.7% of HEM-AP patients, 75% of patients with ACA-AP (P=NS) and 40% of patients with HEM-AP + ACA (P=0.0053). The 24-month failure-free survival rate was 87.5% in HEM-AP patients, 43.8% in ACA-AP patients and 15% in HEM-AP + ACA patients (P=0.022). The 24-month estimate of progression-free survival was 100% in HEM-AP patients, 92.8% in ACA-AP patients and 58.3% in HEM-AP + ACA patients (P=0.0052). In conclusion, frontline imatinib allows favorable outcomes in HEM-AP and ACA-AP patients but appears insufficient for patients with HEM-AP + ACA. Broader-target and/or more potent BCR-ABL tyrosine kinase inhibitors alone or in combination may be considered in this setting.
Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Leucemia Mieloide de Fase Acelerada/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Benzamidas , Feminino , Humanos , Mesilato de Imatinib , Leucemia Mieloide de Fase Acelerada/mortalidade , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The hemophagocytic syndrome is rare and sometimes associated with tuberculosis. OBSERVATION: We report the case of a 30-year-old migrant from Congo presenting with a recurrent right pleuropneumonia, cachexia and night sweat. Blood tests revealed bicytopenia with a normal myelogram. Thorax CT-scan showed large mediastinal lymph nodes and pleuritis. Mediastinal lymph node biopsy concluded to granulomatosis lymphadenopathy with necrosis and bone marrow biopsy suggested hemophagocytic syndrome. The outcome was favorable with antibiotics and corticosteroids.
Assuntos
Linfo-Histiocitose Hemofagocítica/etiologia , Tuberculose/complicações , Adulto , Humanos , MasculinoRESUMO
Erythropoiesis-stimulating agents (ESAs) remain the first-line treatment of anemia in lower risk myelodysplastic syndromes (MDS) without 5q deletion. A preliminary report suggested that adding all-trans retinoic acid (ATRA) to ESAs may improve their erythroid response, particularly in patients with high endogenous erythropoietin (EPO) level, and may improve other cytopenias. We conducted a prospective multicenter study of EPO-beta and ATRA in anemic MDS patients with marrow blasts <10% and either previous ESA failure or relapse, endogenous EPO >500 U/l or other cytopenia(s) (absolute neutrophilic count <1.0 G/l or platelets <50 G/l). A total of 59 patients were evaluable after 12 weeks of treatment. The erythroid response rates according to IWG 2000 and 2006 criteria, respectively, were as follows: overall: 49 and 36%; patients with previous ESA failure (n=28): 43 and 32%; patients with endogenous EPO >500 U/l (n=18): 11 and 19%; patients transfused >2 red blood cells units/month (n=28) 43 and 39%. Only one neutrophil, but no platelet response, and no major side effect were observed. EPO-beta-ATRA combination appears a possible therapeutic option in anemia of MDS having failed an ESA alone, but not in patients with high endogenous EPO level, and does not improve neutropenia and thrombocytopenia.
Assuntos
Eritropoetina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Tretinoína/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutropenia/tratamento farmacológico , Neutrófilos , Contagem de Plaquetas , Proteínas Recombinantes , Trombocitopenia/tratamento farmacológico , Resultado do Tratamento , Adulto JovemRESUMO
A patient with hairy cell leukemia who developed mediastinal mass and fever is described. A CT-guided aspiration of the mass yielded Salmonella tiphymurium. Granulocyte response to infection was intact and could explain the favorable course of this unusual Salmonella infection. Although several reports deal with salmonellosis as a complication of immunodeficiency states, this type of infection is of rare occurrence in hairy cell leukemia.
Assuntos
Leucemia de Células Pilosas/complicações , Infecções por Salmonella/etiologia , Humanos , Leucemia de Células Pilosas/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
Acute promyelocytic leukemia (APL) is usually associated with the translocation t(15;17)(q22;q12-21), which disrupts the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15. We report a patient with typical APL without the common t(15;17). Cytogenetic studies demonstrated a normal appearance of chromosomes 15, while a small marker seemed to be an i(17q-). Molecular analysis showed RARA and PML rearrangements, suggesting that the chromosome abnormality corresponded to a variant translocation.
Assuntos
Proteínas de Transporte/genética , Cromossomos Humanos Par 15/ultraestrutura , Cromossomos Humanos Par 17/ultraestrutura , Rearranjo Gênico , Leucemia Promielocítica Aguda/genética , Translocação Genética , Adulto , Transplante de Medula Óssea , Feminino , Humanos , Cariotipagem , Leucemia Promielocítica Aguda/cirurgia , Masculino , Receptores do Ácido RetinoicoRESUMO
We conducted a randomized multicenter study to compare the efficacy and safety of two antibiotic regimens (cefepime [2 g b.i.d.] plus amikacin or ceftazidime [2 g t.i.d.] plus amikacin) as first-line therapy for fever in patients with hematologic malignancies and neutropenia. A total of 353 patients were randomized according to a 2:1 (cefepime:ceftazidime) ratio. Two hundred-twelve patients in the cefepime group and 107 in the ceftazidime group (90% of all patients) were evaluable for efficacy. The polymorphonuclear neutrophil count was < 100/mm3 on enrollment for 70% of the patients. The mean duration of neutropenia was 26 days. The efficacy in both study arms was comparable, although a trend in favor of cefepime was seen in terms of therapeutic success (response rate, 27% vs. 21% for the ceftazidime group). The overall response rate after glycopeptides were added to the regimens was 60% for the cefepime group and 51% for the ceftazidime group; the bacterial eradication rates were 81% vs. 76%, respectively, and the rates of new bacterial infections were 14% vs. 18%, respectively. We conclude that the combination cefepime/amikacin is at least as effective as the reference regimen of ceftazidime/amikacin in this setting.
Assuntos
Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Ceftazidima/uso terapêutico , Cefalosporinas/uso terapêutico , Febre/complicações , Febre/tratamento farmacológico , Neoplasias Hematológicas/complicações , Neutropenia/complicações , Neutropenia/tratamento farmacológico , Amicacina/administração & dosagem , Amicacina/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Bacteriemia/diagnóstico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Cefepima , Ceftazidima/administração & dosagem , Ceftazidima/efeitos adversos , Cefalosporinas/administração & dosagem , Cefalosporinas/efeitos adversos , Resistência Microbiana a Medicamentos , Quimioterapia Combinada , Feminino , Gastroenteropatias/microbiologia , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Masculino , Dermatopatias Bacterianas/diagnóstico , Infecções dos Tecidos Moles/diagnóstico , Infecções Urinárias/diagnósticoRESUMO
Few reports are available on the treatment of patients with Waldenström macroglobulinemia (WM) and primary or secondary resistance to alkylating-agent-based regimens. From December 1993 through December 1997, 92 patients with WM resistant to first-line therapy (42) or with first relapse (50) after alkylating-agent therapy were randomly assigned to receive fludarabine (25 mg/m(2) of body-surface area on days 1-5) or cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP; 750 mg/m(2) cyclophosphamide and 25 mg/m(2) doxorubicin on day 1 and 40 mg/m(2) prednisone on days 1-5). The first end point evaluated was the response rate after 6 treatment courses. Forty-five patients received CAP and 45 received fludarabine. Two patients died before the first course of chemotherapy. No statistical differences were observed between the 2 treatment arms with respect to hematologic toxicity or infections. Mucositis and alopecia occurred significantly more often in patients treated with CAP. Partial responses were obtained in 14 patients (30%) treated with fludarabine and 5 patients (11%) treated with CAP (P =.019). Responses were more durable in patients treated with fludarabine (19 months versus 3 months), and the event-free survival rate was significantly higher in this group (P <.01). Forty-four patients died, 22 in the fludarabine group and 22 in the CAP group. There was no statistical difference in the median overall survival time in the 2 study arms. Fludarabine was thus more active than CAP in salvage therapy of WM and should be tested as first-line therapy in a randomized comparison with alkylating agents.