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1.
Crit Rev Microbiol ; 39(3): 310-24, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22917084

RESUMO

Mucormycosis is an emerging invasive fungal infection, primarily affecting immunocompromised patients. The disease is difficult to diagnose and mortality reaches 40% even if treated adequately. Depending on site of infection and risk factors, surgical debridement in combination with systemically active antifungal drugs are the mainstay treatment strategies. Lipid-based amphotericin B is the treatment of choice for first-line therapy while posaconazole may be a promising alternative. We performed a PubMed search on reports of patients with mucormycosis treated with posaconazole. From 2003 to 2011, 96 cases have been published. Diagnosis was based on histology alone in 2 (2.1%) and microbiological evidence in 67 (69.8%), while no data on the diagnostic approach was reported in 27 (28.1%) patients. The most frequent pathogens were Rhizopus spp. (31.2%), followed by Mucor spp. (14.6%). The site of infection was predominantly rhino-orbital (38.5%, of which 43% also had central nervous system [CNS] involvement), followed by disseminated disease (22.1%). A complete response was achieved in 62 (64.6%), partial response in 7 (7.3%) patients, and stable disease in 1 (1%). Overall mortality was 24% (lacking data for three patients). In published case reports on posaconazole treatment for mucormycosis, the drug was frequently and successfully used in combination or as second line therapy.


Assuntos
Antifúngicos/uso terapêutico , Mucormicose/tratamento farmacológico , Triazóis/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Terapia de Salvação
2.
Histopathology ; 63(6): 788-801, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24117687

RESUMO

AIMS: To reassess the prognostic validity of immunohistochemical markers and algorithms identified in the CHOP era in immunochemotherapy-treated diffuse large B cell lymphoma patients. METHODS AND RESULTS: The prognostic significance of immunohistochemical markers (CD10, Bcl-6, Bcl-2, MUM1, Ki-67, CD5, GCET1, FoxP1, LMO2) and algorithms (Hans, Hans*, Muris, Choi, Choi*, Nyman, Visco-Young, Tally) was assessed using clinical diagnostic blocks taken from an unselected, population-based cohort of 190 patients treated with R-CHOP. Dichotomizing expression, low CD10 (<10%), low LMO2 (<70%) or high Bcl-2 (≥80%) predicted shorter overall survival (OS; P = 0.033, P = 0.010 and P = 0.008, respectively). High Bcl-2 (≥80%), low Bcl-6 (<60%), low GCET1 (<20%) or low LMO2 (<70%) predicted shorter progression-free survival (PFS; P = 0.001, P = 0.048, P = 0.045 and P = 0.002, respectively). The Hans, Hans* and Muris classifiers predicted OS (P = 0.022, P = 0.037 and P = 0.011) and PFS (P = 0.021, P = 0.020 and P = 0.004). The Choi, Choi* and Tally were associated with PFS (P = 0.049, P = 0.009 and P = 0.023). In multivariate analysis, the International Prognostic Index (IPI) was the only independent predictor of outcome (OS; HR: 2.60, P < 0.001 and PFS; HR: 2.91, P < 0.001). CONCLUSIONS: Results highlight the controversy surrounding immunohistochemistry-based algorithms in the R-CHOP era. The need for more robust markers, applicable to the clinic, for incorporation into improved prognostic systems is emphasized.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunoterapia , Linfoma Difuso de Grandes Células B/terapia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Anticorpos Monoclonais Murinos/administração & dosagem , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Terapia Combinada , Ciclofosfamida/administração & dosagem , Proteínas de Ligação a DNA/metabolismo , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Proteínas com Domínio LIM/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Neprilisina/metabolismo , Prednisona/administração & dosagem , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6 , Rituximab , Serpinas/metabolismo , Vincristina/administração & dosagem , Adulto Jovem
3.
Blood ; 115(18): 3664-70, 2010 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-20197551

RESUMO

Enteropathy associated T-cell lymphoma (EATL) is a rare type of peripheral T-cell lymphoma. At present, there are no standardized diagnostic or treatment protocols for EATL. We describe EATL in a population-based setting and evaluate a new treatment with aggressive chemotherapy and autologous stem cell transplantation (ASCT). From 1979 onward the Scotland and Newcastle Lymphoma Group prospectively collected data on all patients newly diagnosed with lymphoma in the Northern Region of England and Scotland. Between 1994 and 1998, records of all patients diagnosed with EATL were reviewed, and 54 patients had features of EATL. Overall incidence was 0.14/100 000 per year. Treatment was systemic chemotherapy (mostly anthracycline-based chemotherapy) with or without surgery in 35 patients and surgery alone in 19 patients. Median progression-free survival (PFS) was 3.4 months and overall survival (OS) was 7.1 months. The novel regimen IVE/MTX (ifosfamide, etoposide, epirubicin/methotrexate)-ASCT [corrected] was piloted from 1998 for patients eligible for intensive treatment, and 26 patients were included. Five-years PFS and OS were 52% and 60%, respectively, and were significantly improved compared with the historical group treated with anthracycline-based chemotherapy (P = .01 and P = .003, respectively). EATL is a rare lymphoma with an unfavorable prognosis when treated with conventional therapies. The IVE/MTX-ASCT regimen is feasible with acceptable toxicity and significantly improved outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Celíaca/terapia , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Celíaca/complicações , Terapia Combinada , Etoposídeo/administração & dosagem , Feminino , Humanos , Ifosfamida/administração & dosagem , Linfoma de Células T Periférico/complicações , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Escócia/epidemiologia , Taxa de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagem
4.
Blood ; 116(12): 2026-32, 2010 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-20551376

RESUMO

For older patients with early unfavorable or advanced stage Hodgkin lymphoma (HL) the prognosis is much worse than for younger HL patients. We thus developed a new regimen, BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone), to improve both tolerability and efficacy of treatment for older HL patients. Between 2004 and 2005, 65 patients with early unfavorable or advanced stage HL aged between 60 and 75 years were enrolled in this phase 2 trial. Treatment consisted of 6 to 8 cycles of BACOPP. Residual tumor masses were irradiated. Primary endpoints were feasibility as determined by adherence to protocol and overall response rate. Secondary endpoints included toxicity, freedom from treatment failure, and progression free and overall survival. For the final analysis 60 patients (92%) were eligible; 75% of treatment courses were administered according to protocol. World Health Organization grade 3/4 toxicities occurred in 52 patients. Fifty-one patients (85%) achieved complete remission, 2 (3%) partial remission, and 4 (7%) developed progressive disease. With a median observation time of 33 months, 18 patients died (30%), including 7 treatment-associated deaths. Three patients died before response assessment. Thus, the BACOPP regimen is active in older HL patients but is compromised by a high rate of toxic deaths. This trial was registered at www.clinicaltrials.gov as #NCT00284271.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Bleomicina/administração & dosagem , Ciclofosfamida , Progressão da Doença , Doxorrubicina/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Alemanha , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Indução de Remissão , Análise de Sobrevida , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagem
5.
Bone Marrow Transplant ; 55(4): 840, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30862820

RESUMO

In the original version of this article, the mention of 'ifosfamide 1500 mg/m2 days 1-3' should, in fact, read 'ifosfamide 1500 mg/m2 bd days 1-3'. This has now been updated in the original version of the article.

6.
Haematologica ; 94(1): 113-22, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19066334

RESUMO

There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).


Assuntos
Neoplasias Hematológicas/complicações , Micoses/complicações , Micoses/prevenção & controle , Antifúngicos/uso terapêutico , Alemanha/epidemiologia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/cirurgia , Hematologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Oncologia , Micoses/tratamento farmacológico , Micoses/epidemiologia , Guias de Prática Clínica como Assunto , Sociedades Médicas , Transplante Homólogo
7.
J Antimicrob Chemother ; 61(4): 939-46, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18272515

RESUMO

BACKGROUND: Intensive chemotherapy with severe neutropenia is associated with invasive fungal infections (IFIs) leading to high mortality rates. During leukaemia induction chemotherapy, IFI often prohibited further curative treatment, thus predisposing for leukaemia relapse. Continuing myelosuppressive chemotherapy after diagnosis of IFI has become feasible with the now expanding arsenal of safe and effective antifungals. Secondary prophylaxis of IFI is widely administered, but reliable data on outcome and risk factors for recurrent IFI during subsequent chemotherapy are not available. This study determines risk factors for recurrent IFI in leukaemia patients. METHODS: From 25 European cancer centres, 166 consecutive patients with acute myelogenous leukaemia (AML) and a recent history of proven or probable pulmonary IFI were included. Patients were followed for recurrence or breakthrough IFI during the subsequent chemotherapy cycle. RESULTS: Of the 166 patients included, 69 (41.6%) were female, the median age was 53 years (range 2-81) the and 3 (1.8%) were <16 years. Recurrent IFI occurred in 26 patients (15.7%). Multiple logistic regressions yielded predisposing factors: duration of neutropenia [per additional day; odds ratio (OR) 1.043, confidence interval (CI) 1.008-1.078], high-dose cytarabine (OR 3.920, CI 1.120-12.706), number of antibiotics (per antibiotic; OR 1.504, CI 1.089-2.086), partial response as outcome of prior IFI (OR 4.037, CI 1.301-12.524) and newly diagnosed AML (OR 3.823, CI 0.953-15.340). Usage of high efficiency particulate air filter appeared protective (OR 0.198, CI 0.036-1.089). CONCLUSIONS: Duration of neutropenia, high-dose cytarabine, prior antibiotic therapy and a partial response to the first IFI therapy were risk factors for recurrent IFI and should be considered in AML patients with prior pulmonary IFI undergoing further chemotherapy.


Assuntos
Antifúngicos/uso terapêutico , Micoses/epidemiologia , Micoses/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioprevenção , Criança , Pré-Escolar , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Resultado do Tratamento
8.
Ann Hematol ; 86(2): 107-15, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17103169

RESUMO

We investigated the addition of rituximab to an intensified salvage program followed by a myeloablative course with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Patients with relapsed or progressive aggressive NHL were treated with two cycles of conventional salvage chemotherapy (DHAP) followed by high-dose sequential chemotherapy (cyclophosphamide, methotrexate with vincristine and etoposide) and a final myeloablative course (BEAM) with ASCT. Rituximab (375 mg/m(2)) was administered at each treatment cycle. This cohort was compared with a historical control group of patients treated with the same chemotherapy but without rituximab. Patients from both groups were matched by duration of first remission and lactate dehydrogenase serum levels. Forty-five patients were treated with chemotherapy and 22 with immunochemotherapy. The overall response rates (ORR) at the final evaluation were 63% for the immunochemotherapy group and 42% for the chemotherapy group (p = 0.330). In the historical controlled analysis freedom from second failure (FF2F) at 2 years in the immunochemotherapy group was 57% and overall survival (OS) was 77%. FF2F in the chemotherapy group was 18% (p = 0.0051) and OS was 37% (p = 0.0051). In the matched-pair analysis, FF2F was 58% in the immunochemotherapy group compared to 16% in the chemotherapy group (p = 0.0517); OS was 74 vs 33%, respectively (p = 0.0424). The toxicity was tolerable and comparable in both groups. The addition of rituximab to an intensified salvage chemotherapy regimen seems to improve the prognosis. However, only prospective randomized trial can offer sufficient data of the value of rituximab in relapsed and refractory aggressive NHL.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Transplante de Células-Tronco , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Murinos , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Rituximab , Transplante Homólogo , Resultado do Tratamento
9.
Int J Antimicrob Agents ; 28(3): 262-5, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16908120

RESUMO

Invasive aspergillosis of the central nervous system has a mortality rate exceeding 90%. We describe a 29-year-old woman with a medical history of chronic polyarthritis who developed a proven rhinocerebral Aspergillus fumigatus infection refractory to first-line treatment with liposomal amphotericin B. The patient responded successfully to salvage combination treatment with voriconazole and caspofungin. Furthermore, for the first time, voriconazole levels in an intracerebral abscess were measured in this patient undergoing voriconazole oral therapy.


Assuntos
Antifúngicos/uso terapêutico , Abscesso Encefálico/tratamento farmacológico , Encéfalo/metabolismo , Neuroaspergilose/tratamento farmacológico , Doenças dos Seios Paranasais/tratamento farmacológico , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/farmacocinética , Artrite/complicações , Aspergillus fumigatus/isolamento & purificação , Encéfalo/microbiologia , Abscesso Encefálico/metabolismo , Abscesso Encefálico/microbiologia , Caspofungina , Cromatografia Líquida , Equinocandinas , Feminino , Humanos , Lipopeptídeos , Imageamento por Ressonância Magnética , Espectrometria de Massas , Neuroaspergilose/metabolismo , Neuroaspergilose/microbiologia , Doenças dos Seios Paranasais/metabolismo , Doenças dos Seios Paranasais/microbiologia , Peptídeos Cíclicos/uso terapêutico , Pirimidinas/farmacocinética , Staphylococcus aureus/isolamento & purificação , Triazóis/farmacocinética , Voriconazol
10.
Clin Cancer Res ; 21(13): 3013-9, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25779949

RESUMO

PURPOSE: Enteropathy-associated T-cell lymphoma (EATL) is a rare intestinal non-Hodgkin lymphoma with a poor, though variable prognosis. The International Prognostic Index (IPI) and the prognostic index for peripheral T-cell lymphoma (PIT) have limited predictive value for outcome of EATL. The purpose of this study was to develop and validate a prognostic model for EATL, which can identify high-risk patients who need more aggressive therapy. EXPERIMENTAL DESIGN: This retrospective multicenter study was based on 92 patients and included 45 patients diagnosed with EATL between 1999 and 2009 from the Netherlands and 47 patients from England and Scotland, diagnosed with EATL between 1994 and 1998. A new EATL prognostic index (EPI) was constructed using the RPART (recursive partitioning and regression trees) procedure. Validation was performed applying the bootstrap method. RESULTS: Three risk groups were distinguished (P < 0.0001): a high-risk group, characterized by the presence of B-symptoms [median overall survival (OS) of 2 months]; an intermediate-risk group, comprising patients without B-symptoms and an IPI score ≥ 2 (7 months); and a low-risk group, representing patients without B-symptoms and an IPI score of 0 to 1 (34 months). Internal validation showed stability of statistical significance and prognostic discrimination. In contrast with the IPI and PIT, the EPI better classified patients in risk groups according to their clinical outcome. CONCLUSIONS: Our new, validated, prognostic model EPI accurately predicts survival outcome in EATL and may be used for patient selection for new therapeutic strategies and evaluation of clinical trials.


Assuntos
Linfoma de Células T Associado a Enteropatia/diagnóstico , Linfoma de Células T Associado a Enteropatia/mortalidade , Linfoma de Células T Associado a Enteropatia/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
12.
J Clin Pathol ; 66(3): 249-52, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23172553

RESUMO

Tissue biopsy specimens in the form of formalin-fixed paraffin-embedded tissue (FFPET) represent a valuable resource for biomarker identification and validation. However, to date, they remain an underused asset due to uncertainty regarding RNA extraction and the reliability of downstream techniques, including quantitative RT-PCR. Recently, much interest has emerged in the study of microRNAs; small single-stranded RNAs with a role in transcriptional regulation, that are thought to be well preserved in FFPET. In this study, we show that microRNA expression is comparable between FFPET and matched fresh-frozen samples (miR-17-5p: p=0.01, miR-92: p=0.003), and demonstrate that no significant deterioration in expression occurs over prolonged FFPET storage (p=0.06). Furthermore, microRNA expression is equivalent dependant on RNA extraction method (p<0.001) or DNAse treatment of total RNA (p<0.001). Finally, we validate miR-24 as a suitable reference microRNA for diffuse large B-cell lymphoma (DLBCL) FFPET studies.


Assuntos
Perfilação da Expressão Gênica , Marcadores Genéticos/genética , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética , Inclusão em Parafina , Fixação de Tecidos/métodos , Biomarcadores Tumorais/genética , Biópsia , Estudos de Coortes , Fixadores , Formaldeído , Humanos , Linfoma Difuso de Grandes Células B/patologia , Kit de Reagentes para Diagnóstico , Padrões de Referência , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Curr Hematol Malig Rep ; 6(4): 231-40, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21912848

RESUMO

Enteropathy-associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma of T-cell origin. The recent 2008 World Health Organization classification of hematologic malignancies distinguishes between two types of EATL. The disease is associated with celiac disease, particularly with its late, adult onset. Currently, there are no standardized diagnostic or treatment protocols for EATL, mostly because of its rarity. Historically, the patients have been treated with anthracycline-based chemotherapy with or without surgery. The outcome of patients with EATL treated with these approaches is poor. The reported death rates in the biggest studies are approximately 80-84%, with median progression-free survival (PFS) of 3.4-6.0 months and overall survival of 7.1-10.0 months. The 5-year PFS ranged from 3.2% to 18% and OS from 19.7% to 20%. The results of a novel induction regimen with ifosfamide, etoposide, and epirubicin alternating with intermediate-dose methotrexate followed by autologous stem cell transplantation (ASCT) are more promising, with a 5-year PFS of 52% and OS of 60%. The alternative approach, with a more common induction with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone followed by ASCT has also delivered promising results, with a 3-year PFS of 52% and OS of 47%. This review summarizes recently published data on epidemiology and clinical features, as well as standard and novel treatments including high-dose chemotherapy with ASCT and their outcome in EATL.


Assuntos
Linfoma de Células T Associado a Enteropatia/terapia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Doença Celíaca/complicações , Doença Celíaca/terapia , Terapia Combinada/métodos , Linfoma de Células T Associado a Enteropatia/classificação , Linfoma de Células T Associado a Enteropatia/epidemiologia , Humanos , Transplante de Células-Tronco
15.
Int J Antimicrob Agents ; 34(5): 446-50, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19700265

RESUMO

Patients surviving invasive fungal disease (IFD) and needing further antineoplastic chemotherapy are at high risk of recurrent fungal infection. In the absence of randomised controlled trials in this area, secondary prophylactic regimens are diverse. From 448 patients registered with the Multinational Case Registry of Secondary Antifungal Prophylaxis, we performed an analysis of patients receiving caspofungin (CAS) or itraconazole (ITC). All patients had an underlying haematological malignancy and had been diagnosed with an episode of IFD earlier in their course of treatment. Data collected comprised demographics, underlying disease, first episode of IFD, antifungal prophylaxis, incidence and outcome of breakthrough IFD and survival. A total of 75 patients were evaluated, comprising 28 receiving CAS and 47 receiving ITC. Patients in the CAS group were more likely to have had progression of underlying disease (32.1% vs. 8.5%; P=0.028) as well as incomplete response of initial IFD at baseline (85.7% vs. 57.4%; P=0.005). Allogeneic stem cell transplantation was more prevalent in patients receiving CAS (46.4% vs. 14.9%; P=0.010). There was no difference in the occurrence of breakthrough IFD between both groups (32.1% vs. 31.9%). Treatment outcomes for recurrent IFD and overall mortality did not differ between groups. Both ITC and CAS were equally effective in preventing second episodes of IFD. Patients with uncontrolled first IFD, uncontrolled underlying disease or those receiving stem cell transplantation were more likely to have received CAS prophylaxis. Despite antifungal prophylaxis, risk of breakthrough IFD was high in both groups.


Assuntos
Antifúngicos/uso terapêutico , Quimioprevenção/métodos , Equinocandinas/uso terapêutico , Neoplasias Hematológicas/complicações , Itraconazol/uso terapêutico , Micoses/prevenção & controle , Adolescente , Adulto , Idoso , Caspofungina , Feminino , Humanos , Lipopeptídeos , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
16.
Blood ; 111(1): 71-6, 2008 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17890456

RESUMO

To date, there is little information on the impact of more aggressive treatment regimen such as BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) on the fertility of male patients with Hodgkin lymphoma (HL). We evaluated the impact of BEACOPP regimen on fertility status in 38 male patients with advanced-stage HL enrolled into trials of the German Hodgkin Study Group (GHSG). Before treatment, 6 (23%) patients had normozoospermia and 20 (77%) patients had dysspermia. After treatment, 34 (89%) patients had azoospermia, 4 (11%) had other dysspermia, and no patients had normozoospermia. There was no difference in azoospermia rate between patients treated with BEACOPP baseline and those given BEACOPP escalated (93% vs 87%, respectively; P > .999). After treatment, most of patients (93%) had abnormal values of follicle-stimulating hormone, whereas the number of patients with abnormal levels of testosterone and luteinizing hormone was less pronounced-57% and 21%, respectively. In univariate analysis, none of the evaluated risk factors (ie, age, clinical stage, elevated erythrocyte sedimentation rate, B symptoms, large mediastinal mass, extranodal disease, and 3 or more lymph nodes) was statistically significant. Male patients with HL are at high risk of infertility after treatment with BEACOPP.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azoospermia/induzido quimicamente , Fertilidade/efeitos dos fármacos , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Bleomicina/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Etoposídeo/efeitos adversos , Hormônio Foliculoestimulante/sangue , Seguimentos , Alemanha , Humanos , Hormônio Luteinizante/sangue , Masculino , Valor Preditivo dos Testes , Prednisona/efeitos adversos , Procarbazina/efeitos adversos , Prognóstico , Contagem de Espermatozoides , Testosterona/sangue , Vincristina/efeitos adversos
17.
J Clin Oncol ; 26(3): 434-9, 2008 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-18086799

RESUMO

PURPOSE: Lymphocyte-predominant Hodgkin's lymphoma (LPHL) is rare and differs in histologic and clinical presentation from classical Hodgkin's lymphoma (cHL). To shed more light on the prognosis and outcome of LPHL, we reviewed all LPHL patients registered in the German Hodgkin Study Group (GHSG) database, comparing patient characteristics and treatment outcome with cHL patients. PATIENTS AND METHODS: We analyzed retrospectively 8,298 HL patients treated within the GHSG trials HD4 to HD12, of whom 394 had LPHL and 7,904 had cHL. RESULTS: Complete remission and unconfirmed complete remission after first-line treatment was achieved in 91.6% v 85.9% of patients in early favorable stages, 85.7% v 83.3% of patients in early unfavorable stages, and 76.8% v 77.8% of patients in advanced stages of LPHL compared with cHL, respectively. Tumor control (freedom from treatment failure [FFTF]) for LPHL and cHL patients at a median observation of 50 months was 88% and 82% (P = .0093) and overall survival (OS) was 96% and 92%, respectively (P = .0166). In LPHL patients, negative prognostic factors were advanced stage (P = .0092), Hb less than 10.5 g/dL (P = .0171), and lymphopenia (P = .010) for FFTF. Age >or= 45 years (P = .0125), advanced stage (P = .0153), and Hb less than 10.5 g/dL (P = .0014) were negative prognostic factors for OS. CONCLUSION: The better prognosis of LPHL as compared with cHL might allow different treatment strategies, particularly for early-stage LPHL patients.


Assuntos
Doença de Hodgkin/patologia , Linfócitos/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Intervalo Livre de Doença , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
18.
J Clin Oncol ; 25(15): 2000-5, 2007 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-17420510

RESUMO

PURPOSE: To evaluate treatment outcome of patients with early-stage favorable Hodgkin's lymphoma (HL) who experience disease relapse after primary treatment with two cycles of chemotherapy followed by radiotherapy (RT). PATIENTS AND METHODS: Of 1,129 patients with early-stage favorable HL enrolled onto the HD7/HD10/HD13 trials of the German Hodgkin Study Group, 42 patients were identified with treatment failure, of whom eight had primary progressive disease, seven had early relapse (< or = 12 months), and 27 had late relapse (> 12 months). We analyzed this group of patients for risk factors, salvage therapy, and treatment outcome. RESULTS: The median age was 41 years (range, 19 to 72 years); 24 patients were male, 15 patients had outfield relapse, 13 patients infield relapse, and nine patients outfield and infield relapse. At relapse, 24 patients were treated with conventional salvage chemotherapy, 14 patients were treated with high-dose chemotherapy followed by autologous stem-cell transplantation, and four patients were treated with RT alone. At 36 months median follow-up, freedom from second treatment failure (FF2F) and overall survival (OS) were 52% and 67%, respectively. According to the prognostic score for relapsed HL (duration of first remission, clinical stage, and anemia at relapse), patients with two or three poor prognostic features had a significantly worse outcome compared with patients with none or one of these factors (P < .05 for FF2F and OS). CONCLUSION: Relapse after primary treatment with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine followed by RT is rare. In our analysis, results were influenced by a high treatment-related mortality rate. Additional studies are needed to define the optimal salvage therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Idoso , Terapia Combinada , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Taxa de Sobrevida , Fatores de Tempo
19.
Leuk Lymphoma ; 50(10): 1726-30, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19639513
20.
Ann Hematol ; 82 Suppl 2: S186-200, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-13680164

RESUMO

Morbidity and mortality in patients with malignancies, especially leukemia and lymphoma, are increased by invasive fungal infections. Since diagnosis of invasive fungal infection is often delayed, antifungal prophylaxis is an attractive approach for patients expecting prolonged neutropenia. Antifungal prophylaxis has obviously attracted much interest resulting in dozens of clinical trials since the late 1970s. The non-absorbable polyenes are probably ineffective in preventing invasive fungal infections, but may reduce superficial mycoses. Intravenous amphotericin B and the newer azoles were used in clinical trials, but their role in antifungal prophylaxis is still not well defined. Allogeneic stem cell transplant recipients are at particularly high risk for invasive fungal infections. Other well described risk factors are neutropenia >10 days, corticosteroid therapy, sustained immunosuppression, graft versus host disease, and concomitant viral infections. The enormous study efforts are contrasted by a scarcity of risk stratified evidence based recommendations for clinical decision making. The objective of this review accumulating information on about 10.000 patients is to assess evidence based criteria primarily regarding the efficacy of antifungal prophylaxis in neutropenic cancer patients.


Assuntos
Neoplasias Hematológicas/terapia , Micoses/prevenção & controle , Neoplasias/terapia , Medicina Preventiva , Humanos
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