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1.
Cytometry B Clin Cytom ; 94(2): 312-326, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-27784127

RESUMO

BACKGROUND: Bone marrow examination has been the confirmatory test for congenital dyserythropoietic anemia type II (CDAII). Occasional spherocytes on peripheral blood smear can confound the diagnosis. Since a screening test is still unavailable, we explored the feasibility of using flow cytometry as a preliminary screening method. METHODS: Thirteen monoclonal antibodies with specificities for eight erythrocyte membrane proteins were used in FACS analysis to probe the cellular features of red cells from CDAII, normal adults, hereditary spherocytosis (HS), and cord red cells. Confocal microscopy was performed on normal and CDAII to determine the overall distribution of CD44 and CD47. Their expression levels on cultured erythroblasts were also analyzed. RESULTS: The densely stained band 3 as seen in CDAII in gel electrophoresis was also obtained for Dantu phenotype. Likewise analysis of CDAII cases (n = 26) using the eosin-5'maleimide (EMA) binding test found 57% of patients giving results either positive or in the grey area for HS. Enhanced fluorescence of CD44 was detected in 96% of the CDAII patients, and anti-CD47 binding was also elevated to a lesser degree. Although RNA expressions of CD44 and CD47 in the cultured erythroblasts of normal controls and CDAII were similar, confocal microscopy revealed more CDAII red cells giving elevated fluorescence than normal red cells. CONCLUSIONS: A distinction between CDAII and HS can be made using the EMA Binding test and anti-CD44 binding. Confirmation of CDAII can subsequently be made based on clinical presentation together with either bone marrow examination or DNA sequencing of SEC23B. © 2016 International Clinical Cytometry Society.


Assuntos
Anemia Diseritropoética Congênita/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular/fisiologia , Receptores de Hialuronatos/metabolismo , Esferocitose Hereditária/metabolismo , Antígeno CD47/metabolismo , Eritrócitos/metabolismo , Feminino , Citometria de Fluxo/métodos , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Fenótipo
2.
Leukemia ; 30(3): 562-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26464170

RESUMO

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.


Assuntos
Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Família , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Risco , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento
3.
Pediatr Blood Cancer ; 61(4): 743-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24123799

RESUMO

Congenital dyserythropoietic anemias are rare hematological disorders leading to ineffective erythropoiesis with chronic anemia, complicated by iron overload. Here we present a remarkable clinical course of an infant with CDA type II who first presented as a severe fetal hydrops, requiring serial intrauterine red cell transfusions. While postnatal transfusion dependency persisted, the patient was successfully transplanted with a myeloablative conditioning regimen and peripheral blood stem cells of a matched donor. We believe that allogeneic HSCT is a reasonable therapeutic approach for patients with very severe CDA, even if only a matched unrelated donor is available.


Assuntos
Anemia Diseritropoética Congênita/terapia , Transfusão de Sangue Intrauterina , Transplante de Células-Tronco , Terapia Combinada , Feminino , Humanos , Lactente , Gravidez , Prognóstico , Condicionamento Pré-Transplante
5.
Dtsch Med Wochenschr ; 134(17): 897-902, 2009 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-19337961

RESUMO

Overwhelming Post-Splenectomy Infection (OPSI or PSS), most frequently caused by encapsulated Gram-positive pathogens, is a complication after splenectomy. Reasons for splenectomy include trauma, or malignant and non-malignant hematologic diseases. OPSI-inducing bacteria are mainly Streptococcus pneumoniae and less frequently Haemophilus influenzae, Neisseria meningitides and Gram-negative bacilli. There exist very efficient--albeit often neglected--strategies, how to prevent infections in patients after splenectomy. These include vaccination, prophylactic antibiotics (always for 3 years during childhood and adolescence) and prompt antibiotic treatment, if an infection is suspected. Patients need to know the nature and likelihood of PSS and they should seek immediate medical attention if they become ill or febrile. Each patient should carry at all times a letter or card documenting the splenectomy. With these measures and precautions, the PSS-risk can be significantly reduced or at best be completely avoided.


Assuntos
Infecções Bacterianas/prevenção & controle , Baço/fisiopatologia , Esplenectomia/efeitos adversos , Trombose/prevenção & controle , Antibioticoprofilaxia , Infecções Bacterianas/etiologia , Vacinas Bacterianas , Humanos , Vacinas contra Influenza , Influenza Humana/etiologia , Influenza Humana/prevenção & controle , Malária/prevenção & controle , Fatores de Risco , Baço/imunologia , Baço/lesões , Esplenopatias/cirurgia
8.
Am J Ind Med ; 51(4): 246-57, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18270999

RESUMO

BACKGROUND: The Northern Germany Leukemia and Lymphoma Study (NLL) is a population-based study designed to provide a quantitative basis for investigations into occupational and environmental risk factors for leukemia and lymphoma. METHODS: All incident cases of leukemia and lymphoma diagnosed between 1/1/1986 and 12/31/1998 in six counties in Northern Germany were actively ascertained. Controls were selected from population registries. Use of pesticides, sources of food supply, time spent at home and work, medical and family history were assessed via face-to-face interview. This self-reported information was used in conjunction with direct environmental measurements of pesticides in household dust and electromagnetic fields (EMFs). In addition, geographical information system (GIS) data were used to derive estimates of environmental exposure to pesticides, EMFs associated with transmission lines, and ionizing radiation from routine nuclear power reactor operations. Occupational exposure assessment was based on lifetime work history. For each job, information on branch of industry, company, job description, and duration of employment were ascertained. RESULTS: Fourteen hundred thirty cases and 3041 controls were recruited. Lifetime residential and workplace histories totaled 49,628 addresses. Occupational exposure to pesticides was reported by 15% of the male participants (women: 16%). Four percent of the men (women: 8%) were occupationally exposed to ionizing radiation for >or=1 year over their lifetime. Sixty four percent of the participants had lived in the vicinity (20 km) of a nuclear power plant in operation. CONCLUSIONS: The NLL illustrates the successful application of innovative methods to simultaneously assess occupational and environmental risk factors for leukemia and lymphoma including radiological hazards, pesticides, and EMFs.


Assuntos
Exposição Ambiental/efeitos adversos , Leucemia/epidemiologia , Linfoma não Hodgkin/epidemiologia , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Poeira , Campos Eletromagnéticos , Feminino , Sistemas de Informação Geográfica , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Praguicidas/toxicidade , Fatores de Risco
9.
Ann Hematol ; 86(4): 239-44, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17256145

RESUMO

Three consecutive polycythemia vera (PV) patients were analyzed before and during pegylated-interferon (rIFNalpha) treatment for the following markers: (1) granulocyte and CD34(+) cell clonality, (2) Jak2V617F expression, (3) PRV-1 mRNA overexpression, and (4) Epo-independent colony (EEC) growth. Before rIFNalpha therapy, all patients displayed clonal hematopoiesis, 100% Jak2V617F expression as well as PRV-1 overexpression, and EEC growth. After rIFNalpha treatment, all three patients demonstrated polyclonal hematopoiesis. Nonetheless, Jak2V617F expression, PRV-1 overexpression, and EEC-growth remained detectable, albeit at lower levels. We conclude that reemergence of polyclonal hematopoiesis after rIFNalpha treatment may be achieved in a substantial proportion of patients. However, this does not constitute elimination of the PV clone. These data demonstrate the usefulness of novel markers in monitoring minimal residual disease and caution against discontinuation of rIFNalpha treatment after hematologic remission. Long-term follow-up of large patient cohorts is required to determine whether rIFNalpha treatment can cause complete molecular remissions in PV.


Assuntos
Biomarcadores/análise , Interferon-alfa/uso terapêutico , Policitemia Vera/tratamento farmacológico , Adulto , Substituição de Aminoácidos , Antígenos CD34/análise , Proliferação de Células/efeitos dos fármacos , Células Clonais , Eritropoetina/farmacologia , Feminino , Proteínas Ligadas por GPI , Expressão Gênica/efeitos dos fármacos , Granulócitos/citologia , Granulócitos/efeitos dos fármacos , Granulócitos/imunologia , Hematopoese/efeitos dos fármacos , Hematopoese/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Isoantígenos/genética , Janus Quinase 2/genética , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas Mutantes/genética , Policitemia Vera/genética , Policitemia Vera/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
10.
Acta Haematol ; 117(2): 115-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17127819

RESUMO

A transient aplastic crisis (TAC) is a well-known complication in all types of chronic hemolytic anemia but only 2 cases of such an event were described in congenital dyserythropoietic anemias (CDAs). Here, we report a third case, and by retrospective chart review of 78 cases we found evidence of TAC in 8 further patients with CDA II, with serological evidence of previous human parvovirus B19 (B19V) infection in all but one. Although B19V infection results in TAC in only a minority of patients with CDA, physicians responsible for these patients should be aware of such a potentially life-threatening complication. Testing for B19V-specific IgG is recommended in patients with CDA to estimate the risk of a possible future aplastic crisis.


Assuntos
Anemia Diseritropoética Congênita/complicações , Aplasia Pura de Série Vermelha/etiologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/análise , Criança , Pré-Escolar , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/complicações , Parvovirus B19 Humano/imunologia
11.
Bone Marrow Transplant ; 38(7): 493-9, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16980997

RESUMO

Ovarian cancer is chemosensitive, but most patients with advanced disease die from tumor progression. As 25% of the patients can be cured by chemotherapy, it is reasonable to evaluate high-dose chemotherapy (HDCT). Forty-eight patients with untreated ovarian cancer were entered in a multicenter phase I/II trial of multicycle HDCT. Median age was 46 (19-59 years); International Federation of Gynecology and Obstetrics-stage was III in 79% and IV in 21%; 31% had residual disease >1 cm after surgery. Two courses of induction/mobilization therapy with cyclophosphamide (250 mg/m2) and paclitaxel (250 mg/m2) were used to collect peripheral blood stem cells. HDCT consisted of two courses of carboplatin (area under curve (AUC) 18-22) and paclitaxel followed by one course of carboplatin and melphalan (140 mg/m2) with or without etoposide (1600 mg/m2). Main toxicity was gastrointestinal. Limiting carboplatin to AUC 20 and eliminating etoposide resulted in manageable toxicity (69% without grade 3/4 toxicity). One patient died from treatment-related pneumonitis. At 8 years median follow-up, median progression-free-survival (PFS) and overall survival (OS) is 13.3 and 37.0 months. Five-years PFS and OS is 18 and 33%. Multicycle HDCT is feasible in a multicenter setting. A European phase III trial based on this regimen is evaluating the efficacy of HDCT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Transplante de Células-Tronco de Sangue Periférico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Resultado do Tratamento
13.
Leukemia ; 19(6): 984-9, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15830009

RESUMO

Gender-related aspects in chronic myeloid leukemia (CML) have not been studied well. We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan) and II (IFN+HU vs HU alone). The median observation time was 8.6 years. A total of 503 patients (59%) were male. Female patients were older (51 vs 46 years; P<0.0001), presented with lower hemoglobin (11.7 vs 12.5 g/dl; P<0.0001), higher platelet counts (459 vs 355 x 10(9)/l; P<0.0001), smaller spleen size (3 vs 4 cm below costal margin; P=0.0097), a lower rate of additional cytogenetic aberrations (9 vs 15%; P=0.018) and a less favorable risk profile (P=0.036). The transplantation rate was 14% for female (n=48) and 22% for male patients (n=113). Median survival was longer in female patients (58 vs 49 months; P=0.035) mainly attributable to better survival in the low- and intermediate-risk groups and, independent from risk groups, in the HU group. These results were confirmed by matched-pair analyses based on German population data (n=496, 59 vs 45 months; P=0.0006). This is the first analysis of gender aspects in CML using randomized trials. It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Caracteres Sexuais , Adulto , Distribuição por Idade , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Causas de Morte , Feminino , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Análise de Sobrevida , Resultado do Tratamento
16.
Leukemia ; 18(9): 1460-7, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15284854

RESUMO

Bone marrow fibrosis (MF) has been shown to indicate therapy failure in Ph(+) chronic myeloid leukemia (CML). However, the results on the development of MF during interferon-alpha therapy of CML are controversial. The significance of the interferon dose has not been considered as yet. In total, 627 bone marrow biopsies taken prospectively from 200 patients with CML recruited in two studies using different doses of interferon-alpha +/- low-dose cytosine arabinoside were examined for MF before and during therapy. The results showed that the risk of MF depended significantly on the interferon-alpha dose applied (P<0.000005). MF progressed during low-dose therapy (3 x 5 x 10(6) IU/week), but was prevented from progression when applying high dose (5 x 10(6) IU/m(2)/per day). MF disappeared when high-dose interferon-alpha was combined with low-dose cytosine arabinoside (P<0.000005). The risk of death markedly increased when MF occurred or progressed (P<0.0009), independent of all other prognostic factors evaluated including the cytogenetic response. In conclusion, the effectiveness of interferon-alpha on MF depends on the treatment intensity. MF reverses when combining high-dose interferon-alpha with low-dose cytosine arabinoside, but progresses when applying low-dose interferon-alpha. MF appears to be a significant early indicator of ineffective therapy in CML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Mielofibrose Primária/etiologia , Adulto , Biópsia , Aberrações Cromossômicas , Ensaios Clínicos Controlados como Assunto , Citarabina/administração & dosagem , Análise Citogenética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Interferon-alfa/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
17.
Ann Hematol ; 83(6): 364-70, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15034760

RESUMO

Essential thrombocythemia (ET) is a heterogeneous disorder. For example, the growth of erythropoietin-independent erythroid colonies, termed "endogenous erythroid colonies (EECs)", has previously been observed in only 50% of ET patients. We have recently described the overexpression of a hematopoietic receptor, PRV-1 (polycythemia rubra vera-1), in patients with polycythemia vera (PV). Here, we compare PRV-1 expression and EEC formation in a cohort of 30 patients with ET; 50% of the ET patients in our cohort displayed EEC growth. Likewise, 50% of the ET patients overexpressed PRV-1. Remarkably, only the 15 ET patients displaying EEC growth showed elevated PRV-1 expression, while the 15 EEC-negative ET patients expressed normal PRV-1 levels. It has previously been reported that EEC-positive ET patients develop PV during long-term follow-up. Here, we show that 40% of the PRV-1-positive patients develop symptoms of PV during the course of their disease. In contrast, none of the 15 PRV-1-negative patients displayed such symptoms (p=0.017). Moreover, PRV-1-positive patients had a significantly higher number of thromboembolic or microcirculatory events (p=0.003). We propose that PRV-1-positive ET comprise a pathophysiologically distinct subgroup of patients, one that is at risk for the development of complications and for the emergence of PV.


Assuntos
Isoantígenos/biossíntese , Glicoproteínas de Membrana/biossíntese , Policitemia Vera/diagnóstico , RNA Mensageiro/biossíntese , Trombocitemia Essencial/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Northern Blotting , Estudos de Coortes , Diagnóstico Diferencial , Células Precursoras Eritroides/citologia , Células Precursoras Eritroides/patologia , Feminino , Proteínas Ligadas por GPI , Expressão Gênica , Humanos , Isoantígenos/genética , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Policitemia Vera/sangue , Policitemia Vera/complicações , Policitemia Vera/patologia , RNA Mensageiro/genética , Receptores de Superfície Celular , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida , Trombocitemia Essencial/sangue , Trombocitemia Essencial/complicações , Trombocitemia Essencial/patologia
18.
Leukemia ; 18(3): 460-5, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14712285

RESUMO

Immunosuppression has recently been proposed for low-risk myelodysplastic syndromes (MDS) to reverse bone marrow failure by inhibiting intramedullary secretion of proapoptotic cytokines. We treated 35 MDS patients (24 refractory anaemia (RA), 10 RA with excess blasts and one chronic myelomonocytic leukaemia) with either horse antithymocyte globulin 15 mg/kg/day or rabbit antithymocyte globulin 3.75 mg/kg/day, each for 5 days. Median age was 63 years (range: 41-75). After 1 to 34+ months of follow-up (mean: 15+), four patients experienced complete haematological responses (CR), six good responses (GR) and two minor responses. All CRs and GRs occurred in patients with RA, in whom both horse and rabbit ATG yielded five responses out of 12 (42%). Time to response varied between 1 and 10 (mean: 3) months. The median duration of response was 9+ (1-17+) months; five patients are in continuing response. In all, 23 patients suffered side effects > degrees II WHO (the degree of toxicity encountered according to the internationally accepted WHO toxicity grading); one patient died 2 weeks after rabbit ATG from rhinocerebral mucormycosis. Parameters that correlated with response were duration of disease and RA subgroup. In our experience, immune-modulating therapy with either horse or rabbit ATG is feasible in patients with RA and short duration of disease.


Assuntos
Soro Antilinfocitário/uso terapêutico , Imunossupressores/uso terapêutico , Síndromes Mielodisplásicas/terapia , Adulto , Idoso , Animais , Feminino , Cavalos , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/imunologia , Estudos Prospectivos , Coelhos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
19.
Leukemia ; 17(12): 2444-53, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14562117

RESUMO

Marrow fibrosis (MF) has rarely been considered in therapy studies on chronic myeloid leukemia (CML), and there is a lack of long-term observations on the basis of sequential bone marrow biopsies (BMBs) taken prospectively during the course of disease. A total of 848 BMBs from 400 patients with Ph(+) CML recruited in the German randomized CML study I were examined for MF before and during therapy. In total, 110 patients had been randomized to receive interferon (IFN)-alpha, and 290 to receive chemotherapy (hydroxyurea (HU): 154, busulfan: 136). During IFN-alpha and HU medication, MF was reduced or did not increase for about 2 years. Evolving or progressive MF was an independent and early predictor of therapy failure about 2 years earlier than indicated by changes in the peripheral blood, spleen size, marrow blast count and cytogenetics (P<0.00005), resulting in a significant shortening of the survival times of patients independent of the type of therapy applied including allografting (multivariate analyses; P<0.00005). The analyzed long-term observations strongly indicate that MF is an independent poor prognostic complication of CML, allowing an early prediction of therapy failure. Consideration of the fiber content in marrow may therefore significantly improve the prediction of therapy efficacy and outcome of disease.


Assuntos
Antineoplásicos/administração & dosagem , Medula Óssea/patologia , Interferon-alfa/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Biópsia , Transplante de Medula Óssea , Bussulfano/administração & dosagem , Aberrações Cromossômicas , Resistencia a Medicamentos Antineoplásicos , Feminino , Fibrose , Seguimentos , Humanos , Hidroxiureia/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Falha de Tratamento
20.
Leukemia ; 17(9): 1820-6, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12970782

RESUMO

Chronic myeloid leukemia (CML) in older patients has not been studied well. To assess the long-term outcome of older patients with Philadelphia- and/or BCR-ABL-positive CML, 199 patients aged >/=60 years representing 23% of 856 patients enrolled in the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan (BU) and II (IFN+HU vs HU alone) were analyzed after a median observation time of 7 years. In all, 45 patients were treated with Bu, 63 with HU, and 91 with IFN. The 5-year survival was 38% in patients >/=60 years and 47% in patients <60 years (P<0.001). Whereas 5-year survival in chemotherapy-treated older patients was inferior to that in younger patients (33 vs 46%, P=0.006 for HU and 29 vs 38%, P=0.042 for Bu), no significant survival difference could be verified in IFN-treated patients (46 vs 53%, P=0.077). Calculation of age-adjusted, relative survival confirmed these results. Adverse effects of IFN were similar in both age groups, but IFN dosage to achieve treatment goals was lower in older patients. We conclude that the course of CML is not different in the elderly. They require lower IFN doses, achieve the same hematologic and cytogenetic response rates and the same survival advantage at comparable toxicity.


Assuntos
Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Proteínas Tirosina Quinases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/uso terapêutico , Criança , Feminino , Seguimentos , Proteínas de Fusão bcr-abl , Humanos , Hidroxiureia/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Taxa de Sobrevida , Resultado do Tratamento
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