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1.
J Cancer Res Clin Oncol ; 142(1): 305-15, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26407768

RESUMO

INTRODUCTION: Treatment of patients (pts) with acute myelogenous leukaemia (AML) above 60 years remains a challenge. We report long-term follow-up of the AML97 study, where pts were registered at diagnosis and received treatment dependent on their comorbidities: dose-intense cytarabine (AraC) and anthracycline in the curative arm, and low-dose chemotherapy in the palliative arm or best supportive care. MATERIALS AND METHODS: A total of 618 pts were enrolled in this protocol (curative 471, palliative 115 and supportive 32). In the curative arm, complete remission (CR) was obtained in 66.8 % of pts and the estimated probability of being alive at 2 years was 0.30 (±0.02 SE). In multivariate analysis, gender (p = 0.005), performance status (p = 0.04) and cytogenetics (p = 0.002) were significant factors for CR. With a median follow-up of 10 (range 0.1-11.8) years, the estimated probability of being event-free after 2 and 5 years according to cytogenetics was 0.48 ± 0.11 and 0.48 ± 0.11 for favourable, 0.20 ± 0.03 and 0.09 ± 0.03 for normal, 0.18 ± 0.06 and 0.10 ± 0.05 for other standard risk and 0.10 ± 0.03 and 0.05 ± 0.02 for unfavourable karyotypes, respectively. The median survival time for pts treated with palliative chemotherapy was 54 and 11 days with best supportive care only. CONCLUSION: In conclusion, treatment of older AML pts with dose-intense AraC is feasible in the majority of pts and induces high rates of CR. Nevertheless, except for favourable karyotype, OS and event-free survival remain low. These results need to be viewed in relation to the new modalities including stem cell transplantation following non-myeloablative conditioning, epigenetic and molecular therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Alemanha , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Cuidados Paliativos , Prognóstico , Indução de Remissão , Taxa de Sobrevida , Fatores de Tempo
2.
Ann Hematol ; 95(3): 473-81, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26696465

RESUMO

We determined the indication, outcome, and risk factors of single and multiple hematopoietic stem cell transplantation(s) (HSCT) in children and adolescents mostly with advanced disease. Forty-one out of 483 patients (8.5 %; median age 9 years) diagnosed at the University of Leipzig with hematological and oncological diseases required HSCT from 1999 to 2011. Patients had overall survival (OS) of 63 ± 10 and 63 ± 16 %, event-free survival (EFS) of 57 ± 10 and 42 ± 16 %, relapse incidence (RI) of 39 ± 10 and 44 ± 18 % and nonrelapse mortality (NRM) of 4 ± 4 and 13 ± 9 % at 10 years after one or more allogeneic and autologous HSCT, respectively. One patient in CR1 and five with advanced disease received two HSCT. Four of the six patients maintained/achieved CR for a median of 13 months. Three died of progression and one of NRM. Two patients had a third HSCT and one survived in CR +231 days after HSCT. Risk factors for OS and EFS were disease stage at HSCT and EBMT risk score. Center (pediatric or JACIE accredited pediatric/adult) was not a determinant for survival. Pediatric single and multiple HSCT are important curative approaches for high-risk malignant diseases with low NRM. Efforts to reduce high RI remain the major aim.


Assuntos
Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Masculino , Taxa de Sobrevida/tendências , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo/métodos , Transplante Homólogo/mortalidade , Resultado do Tratamento , Adulto Jovem
3.
J Cancer Res Clin Oncol ; 141(12): 2193-203, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26129640

RESUMO

PURPOSE: Allogeneic haematopoietic stem cell transplantation (HSCT) is a proven treatment for patients with haematological malignancies. In this retrospective analysis, the impact of donor matching on outcome of unrelated HSCT was analysed in patients transplanted at the University of Leipzig. METHODS: From 2000 to 2009, 206 patients were transplanted from unrelated donors, of which 51 were mismatched (39 in 1 and 12 in ≥ 2 HLA-antigens), using peripheral blood or bone marrow grafts after total body irradiation and cyclophosphamide or busulfan and cyclophosphamide preparative regimens in combination with ATG. For graft-versus-host disease (GvHD) prophylaxis cyclosporine and MTX were administered. RESULTS: After a median follow-up of 49 months, outcome at 5 years in recipients of HLA-identical grafts was comparable to that of patients transplanted from HLA-incompatible donors with an overall survival (OS) of 52 % (95 % CI 43-61) versus 48 % (95 % CI 34-63), respectively (p = 0.48). Results were also comparable for event-free survival at 5 years [47 % (95 % CI 38-56) vs. 39 % (95 % CI 25-54); p = 0.44], relapse incidence (RI) [29 % (95 % CI 20-38) vs. 41 (95 % CI 25-57); p = 0.22] and non-relapse mortality [24 % (95 % CI 16-33) vs. 20 % (95 % CI 8-33); p = 0.84] in the matched versus mismatched groups. Incidence of acute and chronic GvHD was similar in both groups. Advanced disease (p = 0.02) and low-resolution typing (p = 0.04) are risk factors for OS and RI in univariate and multivariate analysis. CONCLUSIONS: Donors with one antigen mismatch are an acceptable option for patients with malignant disease for whom no fully matched donor is available.


Assuntos
Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Histocompatibilidade , Recidiva Local de Neoplasia/mortalidade , Doadores não Relacionados , Adolescente , Adulto , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/imunologia , Antígenos HLA/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
4.
Bone Marrow Transplant ; 46(10): 1296-302, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21132022

RESUMO

With the increasing age of patients undergoing allogeneic hematopoietic cell transplantation (HCT), the age of matched related sibling donors (MRDs) is expected to increase. Donor safety and the impact of donors' age on mobilization, collection of peripheral hematopoietic progenitor cells (HPCs), subsequent engraftment and the incidence of GVHD were retrospectively analyzed. A total of 167 patients received HCT from an MRD. Median donors' age was 48 years (67 (40%) donors were ≥50 years including 34 donors ≥60 years). Side effects under mobilization and apheresis were age independent. Grafts from donors <50 years contained more CD34+ cells (median 9 × 10(6)/kg recipient's body weight (RBW)) compared with older donors (median 5.9 × 10(6)/kg RBW) (P<0.0005), whereas harvests from donors ≥60 years contained more natural killer (NK) cells (P=0.003). Engraftment occurred at a median of 12 days after HCT irrespective of donors' age. Increasing age of MRD did not preclude successful mobilization, collection of HPC and engraftment. In the context of more NK cells in grafts from elderly donors, the impact of donors' age on outcome after HCT warrants further studies. Although short-term toxicities of apheresis were not increased with increasing age, long-term donor safety remains an important issue.


Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/imunologia , Adolescente , Adulto , Idoso , Quimerismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Irmãos , Transplante Homólogo , Adulto Jovem
5.
Leukemia ; 23(4): 635-40, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19151786

RESUMO

Between 1996 and 2004, a total of 708 patients were enrolled in the acute myeloid leukaemia (AML) '96 and '02 studies of the East German Study Group (OSHO). Of these, 138 patients (19.5%) had unfavourable cytogenetics defined as complex karyotype, del (5q)/-5, del (7q)/-7, abn (3q26) and abn (11q23). In all, 77 (56%) achieved complete remission 1 (CR1) after induction chemotherapy and were eligible for haematopoietic cell transplantation (HCT). HCT was performed after a median of two cycles of consolidation chemotherapy (CT) in the AML '96 and one cycle in the AML '02 study (P=0.03). After a median follow-up of 19 months, overall survival (OS) at two years was significantly better in the donor group (52+/-9%) versus the no-donor group (24+/-8%; P=0.005). Differences in outcomes were mainly because of a lower relapse incidence in patients after HCT (39+/-11%) compared with a higher relapse incidence in patients undergoing CT (77+/-10%; P=0.0005). Treatment-related mortality was low and not statistically significantly different between the two treatment groups (15+/-7 and 5+/-5% for HCT and chemotherapy, respectively; P=0.49).We conclude that early HCT from related or unrelated donors led to significantly better OS and leukaemia-free survival compared with chemotherapy in patients with unfavourable karyotype.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Cariotipagem , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
7.
Bone Marrow Transplant ; 35(7): 691-7, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15696178

RESUMO

Assessment of risk factors for acute graft-versus-host disease (aGvHD) might help in tailoring the intensity of prophylactic immunosuppression after allogeneic stem cell transplantation (SCT), thereby decreasing the relapse rate in leukaemia patients. In this study, we analysed whether the number of recipient blood T cells and plasma levels of different cytokines were correlated with the risk of aGvHD after allogeneic SCT. Analyses were performed in 23 patients receiving pSCT immediately before or during the first 2 days of the conditioning regimen. In all, 40 or more Tc-1 cells/microl pretransplant were associated with a significantly increased risk of aGvHD (10/10 patients with GvHD>/=II; 4/13 patients without aGvHD with a Tc-1 number >40/microl, P<0.002, Fisher's exact test). In addition, 40 or more Th-1 cells/microl pretransplant were also associated with a significantly increased risk of aGvHD (P<0.04, Fisher's exact test). Furthermore, the number of Th-2 cells was significantly higher in patients with severe aGvHD even though the median absolute cell counts were very low. However, all other investigated parameters did not reveal predictive value. In conclusion, determination of T-1 cells prior to SCT might determine patients with high/low risk of aGvHD and could thus be used to control immunosuppression after SCT.


Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Contagem de Linfócitos , Valor Preditivo dos Testes , Subpopulações de Linfócitos T , Adulto , Citocinas/sangue , Doença Enxerto-Hospedeiro/etiologia , Humanos , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Condicionamento Pré-Transplante , Transplante Homólogo
8.
J Clin Oncol ; 22(18): 3741-50, 2004 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-15289486

RESUMO

PURPOSE: To evaluate prognostic factors for relapse-free survival (RFS) and overall survival (OS) and to assess the impact of different postremission therapies in adult patients with core binding factor (CBF) acute myeloid leukemias (AML). PATIENTS AND METHODS: Individual patient data-based meta-analysis was performed on 392 adults (median age, 42 years; range, 16 to 60 years) with CBF AML (t(8;21), n = 191; inv(16), n = 201) treated between 1993 and 2002 in prospective German AML treatment trials. RESULTS: RFS was 60% and 58% and OS was 65% and 74% in the t(8;21) and inv(16) groups after 3 years, respectively. For postremission therapy, intention-to-treat analysis revealed no difference between intensive chemotherapy and autologous transplantation in the t(8;21) group and between chemotherapy, autologous, and allogeneic transplantation in the inv(16) group. In the t(8;21) group, significant prognostic variables for longer RFS and OS were lower WBC and higher platelet counts; loss of the Y chromosome in male patients was prognostic for shorter OS. In the inv(16) group, trisomy 22 was a significant prognostic variable for longer RFS. For patients who experienced relapse, second complete remission rate was significantly lower in patients with t(8;21), resulting in a significantly inferior survival duration after relapse compared with patients with inv(16). CONCLUSION: We provide novel prognostic factors for CBF AML and show that patients with t(8;21) who experience relapse have an inferior survival duration.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Ligação a DNA/análise , Leucemia Mieloide/patologia , Leucemia Mieloide/terapia , Fatores de Transcrição/análise , Doença Aguda , Adolescente , Adulto , Transplante de Medula Óssea , Subunidades alfa de Fatores de Ligação ao Core , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Fatores Sexuais , Fator de Transcrição AP-2 , Transplante Autólogo , Transplante Homólogo , Trissomia
9.
Leukemia ; 18(9): 1468-75, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15241437

RESUMO

Kinetics of BCR-ABL transcript elimination and its prognostic implications on relapse were analyzed in patients with chronic myeloid leukemia (CML) after reduced intensity hematopoietic cell transplantation (HCT). In all, 19 CML patients were conditioned with 2 Gy total-body irradiation in combination with (n=14) or without (n=3) fludarabine 3 x 30 mg/m(2) (Flu) or 4.5 Gy total lymphoid irradiation (TLI) with Flu and OKT3 3 x 5 mg (n=2) and were treated with cyclosporine (CSP) and mycophenolate mofetil after allogeneic HCT. BCR-ABL transcripts were analyzed by nested RT-PCR and Taqman((R)) RT-PCR on days +28, +56 and +84 after HCT and were evaluated for their association with relapse. Of the 19 patients, 14 achieved sustained remissions of which six had a negative RT-PCR 28 days after HCT. Five patients relapsed +41, +54, +57, +136 and +234 days after HCT. Predictors for relapse were advanced disease stage (P=0.02) and slow reduction of BCR-ABL transcripts at day 28 (P=0.006) and day 56 (P=0.047) post-transplant. We conclude that a complete clearance of BCR-ABL transcripts is achievable within 4 weeks from HCT even after minimal conditioning and that early kinetics of BCR-ABL transcripts significantly correlate with the probability of hematological relapse.


Assuntos
Proteínas de Fusão bcr-abl/genética , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Ácido Micofenólico/análogos & derivados , Recidiva Local de Neoplasia/diagnóstico , RNA Mensageiro/análise , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Ciclosporina/administração & dosagem , Feminino , Sistema Hematopoético/efeitos dos fármacos , Sistema Hematopoético/efeitos da radiação , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Prognóstico , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Transplante Homólogo , Vidarabina/administração & dosagem , Irradiação Corporal Total
10.
Rofo ; 174(9): 1115-20, 2002 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-12221569

RESUMO

PURPOSE: To investigate the impact of chest radiographs and CT in patients suffering from invasive pulmonary aspergillosis (IPA) compared to the clinical course. PATIENTS AND METHODS: Twenty-three patients with confirmed diagnosis of IPA between January 1996 and September 1999 were included in this study. Signs of inflammatory infiltrates on chest radiographs and CT were retrospectively evaluated in relation to the onset of the clinical symptoms. Infiltrates on CT were analyzed in detail with respect to number, morphology, and localization. RESULTS: Seventy-six infiltrates were found on the CT of 22 patients; one patient had diffuse areas of lung infiltrates. Both lungs were affected by infiltrates in 14 patients. Pleural effusions were confirmed in 12 patients. Twelve patients had typically round foci with halo and nine patients crescent air signs. The preferred localization of lung infiltrates was segment 6. The median interval between the onset of clinical symptoms and the first radiographic changes was 5.5 days, with an additional interval of 4.5 days until confirmation by CT. Localization, number of infiltrates, and clinical course were not related. CONCLUSION: In immune-compromised patients with fever, a CT of the chest should be carried out as soon as possible to detect signs indicative of IPA. Morphological changes on CT like a round focus with halo and crescent air sign support the diagnosis of IPA. In this context, special attention should be directed to pulmonary segment 6.


Assuntos
Aspergilose/diagnóstico por imagem , Pneumopatias Fúngicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Aspergilose/patologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumopatias Fúngicas/patologia , Infecções Oportunistas/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia
11.
Leukemia ; 16(1): 22-9, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11840259

RESUMO

The search for molecular markers in AML that allow prediction of outcome has recently focused on genes involved in the regulation of programmed cell death (PCD). The aim of our study was to determine whether mRNA levels of Mdm-2, Bcl-2, Bcl-x(L), Bad, and Bax are independent prognostic parameters for outcome. Transcript levels were analyzed by real-time quantitative RT-PCR in 232 samples collected either at diagnosis or following induction chemotherapy (ICT). Multivariate COX regression analysis adjusted for chemotherapy protocol, de novo vs secondary AML, and de novo vs relapsed AML indicated: (1) At diagnosis, high expression of Bad (P = 0.015) and even more so high Bax and Bad levels (P = 0.018) predicted adverse outcome, regardless of the response to ICT. In patients who subsequently failed to enter complete remission (CR), high levels of Bad, Bax and Bax high/Bad high were associated with an increased relative risk (RR) to die from tumor (RR = 5.0 for Bad, 3.4 for Bax and 6.14 for Bax high/Bad high). (2) Following ICT, high expression of Bax (P= 0.005) and high Bcl-2/Bax ratios (P = 0.004) were independent predictors of unfavorable outcome, regardless of response to ICT. We conclude that high levels of Bax and Bad correlate with poor outcome, particularly in patients who do not enter CR and may serve as prognostic markers in AML.


Assuntos
Proteínas de Transporte/genética , Leucemia Mieloide/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Doença Aguda , Adolescente , Adulto , Idoso , Apoptose , Sistemas Computacionais , Feminino , Genes bcl-2 , Humanos , Leucemia Mieloide/mortalidade , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-mdm2 , RNA Mensageiro/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento , Proteína X Associada a bcl-2 , Proteína de Morte Celular Associada a bcl , Proteína bcl-X
12.
Bone Marrow Transplant ; 27(11): 1125-32, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11551022

RESUMO

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/normas , Ciclofosfamida/toxicidade , Citarabina/administração & dosagem , Citarabina/normas , Citarabina/toxicidade , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/normas , Fator Estimulador de Colônias de Granulócitos/toxicidade , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Idarubicina/administração & dosagem , Idarubicina/normas , Idarubicina/toxicidade , Interferon-alfa/administração & dosagem , Leucaférese/normas , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia
13.
Mycoses ; 44(9-10): 356-60, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11766098

RESUMO

Pulmonary invasive aspergillosis is frequently difficult to diagnose. In particular, the value of the cultivation of Aspergillus and the Aspergillus galactomannan antigen detection (Pastorex) in bronchoscopically acquired material (bronchoalveolar lavage = BAL, bronchial lavage = BL) in the course of diagnosing this mycosis is viewed controversially. Between January 1996 and September 1999, we obtained 114 positive results in 100 bronchoscopically aquired specimens from a total of 69 patients. 59 of the 69 patients were immunosuppressed, 42 suffered from pulmonary aspergillosis and 38 suffered from invasive pulmonary aspergillosis. The positive prediction rate for a positive result with regard to pulmonary aspergillosis in bronchoscopically acquired material was approximately 61%. Cultivation of Aspergillus was more successful in BAL, and the Aspergillus antigen detection was more successful in BL.


Assuntos
Aspergilose/microbiologia , Aspergillus/isolamento & purificação , Pneumopatias Fúngicas/microbiologia , Antígenos de Fungos/análise , Aspergilose/diagnóstico , Aspergillus/imunologia , Lavagem Broncoalveolar , Galactose/análogos & derivados , Humanos , Pneumopatias Fúngicas/diagnóstico , Mananas/análise , Estudos Retrospectivos
15.
Adv Exp Med Biol ; 457: 177-85, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10500792

RESUMO

Mononuclear cells prepared from peripheral blood or bone marrow of 119 AML and 28 ALL patients prior and following therapy were analyzed for absolute transcript levels of the chemoresistance genes mdr-1 and MRP, and the proto-oncogene bcl-2, by validated contamination-protected quantitative RT-PCR. In newly diagnosed AML mainly tumors of the granulocytic lineage (FAB M1-M2) expressed increased mdr-1 mRNA amounts. The MRP gene was expressed in all investigated samples without relation to a particular FAB class. High initial expression of both genes did not confer a poor prognosis even at high number of CD34+ cells. Data compared prior to and after therapy start (paired samples) revealed that AML patients who did not respond to therapy (NR) expressed increased levels of mdr-1 mRNA, as well as MRP and bcl-2 cDNA normalized to GAPDH reference transcripts, when compared to patients achieving complete remission (CR; p = 0.003, 0.008 and 0.0005, respectively). In ALL-NR the mdr-1 and bcl-2 genes were entirely more active after induction chemotherapy. Arbitrary cut-off values were established in order to delimit pathological from non-pathological gene expression. 59% of studied AML and 33% of ALL-NR exceeded the arbitrary values (mdr-1: > 2 amol/microgram RNA, MRP: > 10 zmol/amol GAPDH, bcl-2: > 5 zmol/amol GAPDH) for one and 11% of AML-NR for two parameters. Only 17% of the AML-CR and none of the ALL-CR group were above these limits. The results indicate that high individual activity of usually one, rarely two of the investigated genes might be associated with poor clinical outcome in treated acute leukemia.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Resistência a Múltiplos Medicamentos/genética , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Transcrição Gênica , Crise Blástica , Células da Medula Óssea/patologia , Genes MDR , Genes bcl-2 , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/patologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proto-Oncogene Mas , RNA Mensageiro/genética , Indução de Remissão , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
16.
Exp Hematol ; 23(14): 1649-54, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8542960

RESUMO

Bone marrow and/or peripheral blood of patients with chronic myeloid leukemia (CML) was investigated by the following three parameters: Ph' chromosome, bcr-abl expression in fresh blood and/or bone marrow, and bcr-abl expression in single hematopoietic progenitor colonies generated from blood and/or bone marrow. Expression of bcr-abl was proven by a reverse "nested primer" polymerase chain reaction (PCR) that is able to detect 1 pg of hybrid mRNA. We performed 108 investigations on 68 patients containing all three parameters: 12 on untreated patients, seven after interferon-alpha (IFN-alpha), seven after low-dose cytosine arabinoside (Ara-C), 22 after cyclic high-dose hydroxyurea (HU), 49 after allogeneic BMT, five before and three after stem cell mobilization, and three after autologous stem cell transplantation (ASCT). In 53 cases (49%), cytogenetics and PCR gave identical results. In 40 cases (37%), PCR from single colonies gave additional information compared to cytogenetics (e.g., mosaic in colonies when all metaphases were positive or negative). Most interesting were the results of one patient after IFN, one patient after ASCT, and 10 patients after BMT (14 investigations = 13%), showing only Ph'-negative mitoses accompanied by a negative nested primer PCR from fresh blood/bone marrow but single bcr-abl-positive progenitor colonies. False-positive results could be widely excluded by repeated insertion of negative controls into the experiments. One explanation for these results could be that CML, progenitors survive in the patient's body by being inactive and not proliferating. These cells express no or very little RNA and bcr-abl is not detectable by reverse PCR. When stimulated ex vivo in a colony assay by external growth factors, cells proliferate and produce detectable amounts of hybrid mRNA. The value of these observations is not clear. A follow-up of the patients will show if such sleeping progenitors can be activated in vivo. Concluding our observations, we can say that in special cases (therapy follow-up, detection of minimal residual disease) it could be useful to perform a PCR analysis of single progenitors in parallel with the routine investigations.


Assuntos
Proteínas de Fusão bcr-abl/genética , Células-Tronco Hematopoéticas/química , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Sequência de Bases , Transplante de Medula Óssea , Citarabina/uso terapêutico , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Humanos , Hidroxiureia/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Dados de Sequência Molecular , Células Tumorais Cultivadas
18.
Artigo em Inglês | MEDLINE | ID: mdl-1713882

RESUMO

Especially in AML but also in ALL a dose reduction during the induction therapy effected distinctly both a diminution of the CR rate and a shortening of the LFS. For these reason reduced treated patients are to exclude from final analysis of study in order to obtain a objective comparison of the four postremission treatment modalities. There was no difference concerning treatment related mortality between "correct" and "reduced" induction therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Doença Aguda , Seguimentos , Humanos , Pessoa de Meia-Idade , Probabilidade , Prognóstico , Indução de Remissão/métodos
19.
Z Gesamte Inn Med ; 44(2): 58-64, 1989 Jan 15.
Artigo em Alemão | MEDLINE | ID: mdl-2650473

RESUMO

The results of therapy in 100 patients who newly fell ill (68 AML, 32 ALL) with acute leukaemia were evaluated (1981 to 1985). The 5-year-survival chance of all patients is 15% for AML, 18% for ALL, first of all it is depending on the degree of remission obtained. The CR rate is nearly 43% (AML) and 66% (ALL), respectively, shows a dependence upon age and is impaired above all by a high early death rate (supportive therapy). With increasing aggressiveness the results of the remission induction therapy improve, as it becomes clear in a comparison with an evaluation of patients 1965-1980 (CR: 15-32%). Also in the postremission therapy the results of intensive forms of therapy are more favourable: 4 years recurrence-free survival after CR in autologous bone marrow transplantation 50%, in allogenic bone marrow transplantation 40%, in cyclic chemotherapy 17%, in oral permanent therapy 0%. Starting from these findings the present conception of the therapy of acute leukaemias is discussed in connection with the literature.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Idoso , Transplante de Medula Óssea , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos
20.
Arch Geschwulstforsch ; 52(1): 57-61, 1982.
Artigo em Inglês | MEDLINE | ID: mdl-7082132

RESUMO

One of the mose important demands on tumour diagnosis is the detection of early and recurring cancer. Recently, immunological tests have revealed possibilities of meeting these expectations. By means of the leukocyte adherence inhibition test (LAI) as tube test we investigated the immunoreactivity of leukocytes of leukocytes to STE in patients with colonic and gastric carcinoma, and the risk groups of Biermer's disease and colonic polyps. As control groups we used 30 blood donors and 37 patients with non malignant colonic diseases. The detection of autoantibodies with the indirect immunofluorescence technique and immune complexes supplemented the immunological investigations. The LAI and STE used are suitable for the diagnosis of gastric and colonic cancer with a rate of accuracy of more than 90 per cent. In the risk groups of colonic polyps the LAI offers a good possibility of detecting early carcinomas, and of monitoring the successful removal of polyps. Problems of autoimmunity in Biermer's disease and colitis ulcerosa do not allow a definite decision regarding a malignant stage in LAI positive patients.


Assuntos
Anemia Perniciosa/imunologia , Neoplasias Gastrointestinais/imunologia , Pólipos Intestinais/imunologia , Adulto , Complexo Antígeno-Anticorpo/análise , Autoanticorpos/análise , Humanos , Teste de Inibição de Aderência Leucocítica , Pessoa de Meia-Idade , Extratos de Tecidos
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