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1.
Br J Haematol ; 196(4): 1018-1030, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34750806

RESUMO

We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
2.
Biol Blood Marrow Transplant ; 25(10): 2079-2085, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31229642

RESUMO

Beyond its impact on bone health, numerous studies have investigated the immune-regulatory properties of vitamin D and shown how its deficiency can affect outcomes in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in acute or chronic graft-versus-host disease. This survey, carried out by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT), describes the current clinical practice discrepancies across the EBMT HSCT programs. We therefore recommend the development of evidence-based guidelines to standardize evaluation criteria and to harmonize the management of vitamin D deficiency in patients undergoing allogeneic HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Deficiência de Vitamina D/terapia , Vitamina D/uso terapêutico , Europa (Continente) , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Inquéritos e Questionários , Transplante Homólogo/métodos , Vitamina D/farmacologia
3.
Ann Oncol ; 29(1): 271-279, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29361136

RESUMO

Background: Cancer mutations generate novel (neo-)peptides recognised by T cells, but the determinants of recognition are not well characterised. The difference in predicted class I major histocompatibility complex (MHC-I) binding affinity between wild-type and corresponding mutant peptides (differential agretopicity index; DAI) may reflect clinically relevant cancer peptide immunogenicity. Our aim was to explore the relationship between DAI, measures of immune infiltration and patient outcomes in advanced cancer. Patients and methods: Cohorts of patients with advanced non-small-cell lung cancer (NSCLC; LUAD, n = 66) and melanoma (SKCM, n = 72) were obtained from The Cancer Genome Atlas. Three additional cohorts of immunotherapy treated patients with advanced melanoma (total n = 131) and NSCLC (n = 31) were analysed. Neopeptides and their clonal status were defined using genomic data. MHC-I binding affinity was predicted for each neopeptide and DAI values summarised as the sample mean DAI. Correlations between mean DAI and markers of immune activity were evaluated using measures of lymphocyte infiltration and immune gene expression. Results: In univariate and multivariate analyses, mean DAI significantly correlated with overall survival in 3/5 cohorts, with evidence of superiority over nonsynonymous mutational and neoantigen burden. In these cohorts, the effect was seen for mean DAI of clonal but not subclonal peptides. In SKCM, the association between mean DAI and survival bordered significance (P = 0.068), reaching significance in an immunotherapy-treated melanoma cohort (P = 0.003). Mean DAI but not mutational nor neoantigen burden was positively correlated with independently derived markers of immune infiltration in both SKCM (P = 0.027) and LUAD (P = 0.024). Conclusions: The association between mean DAI, survival and measures of immune activity support the hypothesis that DAI is a determinant of cancer peptide immunogenicity. Investigation of DAI as a marker of immunologically relevant peptides in further datasets and future clinical studies of neoantigen based immunotherapies is warranted.


Assuntos
Adenocarcinoma de Pulmão/genética , Antígenos de Histocompatibilidade Classe I/genética , Melanoma/genética , Proteínas de Neoplasias/genética , Neoplasias Cutâneas/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/terapia , Estudos de Coortes , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imunoterapia , Melanoma/imunologia , Melanoma/terapia , Proteínas de Neoplasias/imunologia , Estadiamento de Neoplasias , Peptídeos/genética , Peptídeos/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia
4.
Ann Oncol ; 27(12): 2251-2257, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-28007754

RESUMO

BACKGROUND: To evaluate long-term outcome of myeloablative allogeneic stem cell transplantation (allo-SCT) (MAC) versus reduced-intensity allo-SCT (RIC) in patients with relapsed/refractory Hodgkin's lymphoma (HL) in recent years. PATIENTS AND METHODS: A total of 312 patients (63 MAC and 249 RIC) with relapsed/refractory HL who received allo-SCT between 2006 and 2010 and were reported to the EBMT Database were included in the study. RESULTS: With a median follow-up for alive patients of 56 (26-73) months, there were no significant differences in non-relapse mortality (NRM) between MAC and RIC. Relapse rate (RR) was somewhat lower in the MAC group (41% versus 52% at 24 months, P = 0.16). This lower RR translated into a marginal improvement in event-free survival (EFS) for the MAC group (48% versus 36% at 24 months, P = 0.09) with no significant differences in overall survival (73% for MAC and 62% for RIC at 24 months, P = 0.13). Multivariate analysis after adjusting for disease status at the time of allo-SCT showed that the use of MAC was of borderline statistical significance for predicting a lower RR and EFS [HR 0.7, 95% CI (0.5-1.0), P = 0.1] and [HR 0.7, 95% CI (0.5-1.0), P = 0.07], respectively, after allo-SCT. CONCLUSIONS: With modern transplant practices, the NRM associated with MAC for HL has strongly decreased, resulting into non-significant improvement of EFS because of a somewhat better disease control compared with RIC transplants. The intensity of conditioning regimens should be considered when designing individual allo-SCT strategies or clinical trials in patients with relapsed/refractory HL.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Transplante de Células-Tronco/métodos , Transplante Homólogo/métodos , Adulto , Idoso , Medula Óssea , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Doença de Hodgkin/patologia , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Condicionamento Pré-Transplante , Transplante Homólogo/efeitos adversos , Resultado do Tratamento
5.
Br J Cancer ; 108(8): 1560-5, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23511566

RESUMO

The past few years have witnessed something of a renaissance in the field of cancer immunotherapy, relating largely to the clinical advances that have been associated with the development of monoclonal antibodies targeting the immune inhibitory co-receptors CTLA-4 and PD-1 and to the pursuit of genetically modified antigen-redirected adoptive T-cell therapies. These advances are based on a more substantial understanding of the factors restricting effective immune therapies that has been derived from the study of pre-clinical models of tumour growth in immune competent mice. Just as the recognition of the importance of positive co-stimulatory signaling has been instrumental to recent advances in the development of genetically modified antigen-specific adoptive cellular therapies, an increasing awareness of the ability of tumours to subvert multiple immune inhibitory pathways, effectively blunting the development or expansion of any anti-tumour immunity, is fostering the development of novel therapies that appear active as monotherapies but may achieve their greatest impact in combinatorial regimens. This mini-review will focus on attempts to target co-inhibitory members of the immunoglobulin superfamily.


Assuntos
Antígenos de Diferenciação/imunologia , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Animais , Humanos
6.
Clin Infect Dis ; 49(7): 1061-8, 2009 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19705974

RESUMO

BACKGROUND: A retrospective study of the clinical, epidemiologic, and virologic features of norovirus gastroenteritis in 12 adult allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: Norovirus infection was diagnosed by reverse-transcriptase polymerase chain reaction. Strains were genotyped by nucleic acid sequence of the most highly conserved region of the norovirus gene encoding the capsid S (shell) domain. RESULTS: Ten of 12 patients presented with vomiting of short duration, but diarrhea was present in all. The median time from onset to norovirus diagnosis was 1 month (range, 0.25-6.0 months). Eleven patients were receiving immunosuppression when norovirus infection was diagnosed: 8 for graft-versus-host disease (GVHD) in an organ other than gut, 1 for previous gut GVHD, and 2 for presumed gut GVHD that proved to be norovirus gastroenteritis. Six patients required enteral or parenteral nutrition for severe weight loss. In 10 patients, diarrhea lasted a median of 3 months (range, 0.5-14 months) and virus was shed at a high level throughout. The remaining 2 patients died after 4 months of diarrhea (one died of unrelated complications, and the other died of malnutrition). The noroviruses found were GII (untyped), GII-3, GII-4, and GII-7 in 1, 1, 9, and 1 patients, respectively. Eleven of the 12 patients had acquired their infection in the community. Phylogenetic analysis of the GII-4 strains demonstrated that all differed. CONCLUSIONS: Noroviruses are a hitherto unsuspected cause of prolonged morbidity and mortality in adults after allogeneic HSCT. The use of reverse-transcriptase polymerase chain reaction to detect high viral load levels in feces distinguishes norovirus gastroenteritis from gut GVHD.


Assuntos
Infecções por Caliciviridae/epidemiologia , Gastroenterite/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Norovirus/isolamento & purificação , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Infecções por Caliciviridae/virologia , Fezes/virologia , Feminino , Gastroenterite/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Norovirus/classificação , Norovirus/genética , RNA Viral/genética , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Análise de Sequência de DNA , Adulto Jovem
7.
Clin Exp Immunol ; 157(1): 9-19, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19659765

RESUMO

The generation and maintenance of immune responses are controlled by both co-stimulatory and co-inhibitory signalling through T cell co-receptors, many of which belong to the immunoglobulin-like superfamily or the tumour necrosis factor receptor superfamily. Agonistic or antagonistic monoclonal antibodies targeting these co-receptors have the potential to enhance immunity. Furthermore, their activity on the immunosuppressive regulatory T cell populations which are prevalent within many tumours provides an additional rationale for their use as anti-cancer therapies. This review summarizes the interactions between cancer and the immune system, highlighting the ways in which these new classes of immunostimulatory antibodies might enhance anti-tumour immunity and summarizing early clinical experience with their use.


Assuntos
Imunoterapia/métodos , Neoplasias/terapia , Animais , Anticorpos Monoclonais/uso terapêutico , Antígenos CD/imunologia , Antígeno CTLA-4 , Humanos , Imunoglobulinas/imunologia , Ativação Linfocitária , Neoplasias/imunologia , Linfócitos T Reguladores/imunologia , Fator de Necrose Tumoral alfa/imunologia
8.
Bone Marrow Transplant ; 41(9): 765-70, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18195684

RESUMO

This study compares outcome of reduced-intensity conditioned transplant (RIT) with outcome of conventional non-transplant therapy in patients with Hodgkin's lymphoma relapsing following autograft. There were 72 patients in two groups who had relapsed, and received salvage therapy with chemotherapy+/-radiotherapy. One group (n=38) then underwent alemtuzumab-containing RIT. The second group-historical controls (n=34), relapsing before the advent of RIT-had no further high-dose therapy. This group was required to respond to salvage therapy and live for over 12 months post-relapse, demonstrating potential eligibility for RIT, had this been available. Overall survival (OS) from diagnosis was superior following RIT (48% at 10 years versus 15%; P=0.0014), as was survival from autograft (65% at 5 years versus 15%; P< or =0.0001). For the RIT group, OS at 5 years from allograft was 51%, and in chemoresponsive patients was 58%, with current progression-free survival of 42%. Responses were seen in 8 of 15 patients receiving donor lymphocyte infusions (DLI) for relapse/progression, with durable remission in five patients at median follow-up from DLI of 45 months (28-55). These data demonstrate the potential efficacy of RIT in heavily pre-treated patients whose outlook with conventional therapy is dismal, and provide evidence of a clinically relevant graft-versus-lymphoma effect.


Assuntos
Efeito Enxerto vs Tumor , Doença de Hodgkin/mortalidade , Doença de Hodgkin/prevenção & controle , Transplante de Células-Tronco , Condicionamento Pré-Transplante , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Transplante Autólogo , Transplante Homólogo
9.
Clin Pharmacol Ther ; 82(3): 325-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17637786

RESUMO

Bone marrow transplantation has evolved significantly over the past 40 years. The initial rationale of using donor bone marrow to guarantee a supply of hematopoietic stem cells uncontaminated by tumor remains a relevant principle today. However, the donor hematopoietic cells also exert an important immunological, therapeutic effect in the recipient. This synopsis will consider the balance of conditioning therapy intensity and immunological effect of allogeneic stem cell transplantation, informing the positioning of these approaches in current treatment algorithms.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco/tendências , Humanos , Leucemia/terapia , Linfoma/terapia , Mieloma Múltiplo/terapia , Doadores de Tecidos
10.
Leuk Lymphoma ; 48(5): 881-4, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17487730

RESUMO

Treatment options for patients who relapse following autologous transplantation for Hodgkin's lymphoma are limited. There are anecdotal reports of lengthy remissions following second autologous procedures, although treatment-related toxicity can be significant. We report a single centre experience of second autologous transplant performed in seven highly selected patients, who relapsed following initial high-dose therapy. They were all young and had slow tempo disease, which was still sensitive to conventional dose chemotherapy. All received BEAM conditioning for the first transplant, and six of the seven received BEAM for the second. All six of these patients regenerated successfully and with no delay, the final patient dying during the procedure following alternative conditioning. Only one case of presumed carmustine-related pneumonitis was seen, which responded rapidly to corticosteroid therapy. Four patients have subsequently relapsed, of whom three have died at 29, 33, and 38 months postprocedure. One is alive with active disease at 68 months, and the final two are alive and in continuing complete remission at 104 and 68 months.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Transplante Autólogo/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carmustina/uso terapêutico , Citarabina/uso terapêutico , Feminino , Seguimentos , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/mortalidade , Humanos , Masculino , Melfalan/uso terapêutico , Podofilotoxina/uso terapêutico , Prognóstico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Condicionamento Pré-Transplante
12.
Bone Marrow Transplant ; 35(11): 1065-9, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15806119

RESUMO

Patients undergoing haemopoietic stem cell transplants (HSCT) are at high risk of varicella zoster virus (VZV) reactivation, with a significant incidence of dissemination. This study reports a retrospective analysis of 247 allogeneic HSCT recipients receiving anti-viral prophylaxis with low-dose oral aciclovir 400 mg/day, administered until immunosuppression was discontinued and the CD4(+) cell count exceeded 200/mm(3). Viral reactivation was successfully suppressed by aciclovir prophylaxis, with only one case of breakthrough infection. The cumulative incidence of zoster infection at 1 year post transplant was 2% and at 5 years 34%. In all, 64 patients discontinued prophylaxis. Zoster developed in 26 of these, giving a cumulative incidence of infection at 1 year after stopping aciclovir of 39% and at 3 years 44%. Infection occurred in a localised dermatomal distribution in 93% of cases. This supports previous findings that aciclovir prophylaxis prevents early VZV reactivation, although the long-term incidence is not affected as infection occurs once prophylaxis is discontinued. Such infection, however, is mild and localised. This study does not support the idea that use of such low-dose aciclovir regimens reduces the zoster incidence by permitting subclinical reactivation during prophylaxis, and therefore the re-establishment of protective anti-viral immunity.


Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Varicela/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3/metabolismo , Transplante Homólogo/efeitos adversos , Adulto , Linfócitos T CD4-Positivos/citologia , Varicela/etiologia , Estudos de Coortes , Herpes Zoster/etiologia , Humanos , Imunossupressores/farmacologia , Leucemia/terapia , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Linfócitos T/metabolismo , Fatores de Tempo , Condicionamento Pré-Transplante/métodos
13.
Best Pract Res Clin Haematol ; 14(4): 723-39, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11924918

RESUMO

Allogeneic stem cell transplantation (SCT) has become the treatment of choice for some patients with haematological malignancies, allowing dose escalation of chemo-radiotherapy beyond the limits imposed by bone marrow toxicity. However, it is now apparent that dose escalation alone does not eradicate the malignancy in many cases and that an associated immune-mediated graft-versus-malignancy effect may be equally important. Its presence is supported by the following observations: anecdotal reports that patients with relapsed leukaemia following SCT may re-enter remission after withdrawal of immunosuppressive drugs; the lower risk of relapse associated with the development of graft-versus-host-disease (GVHD); and an increased risk of relapse in patients receiving syngeneic transplants or T-cell depleted allogeneic marrow grafts. More directly compelling evidence has been provided by the efficacy of donor lymphocyte infusions, particularly for relapsed chronic-phase CML. Issues that remain to be resolved include the precise nature of the effector cells and their target antigens, the best strategies for separating graft-versus-malignancy from GVHD, the role of adjuvant chemotherapy/cytokines, and the role of non-myeloablative transplantation.


Assuntos
Efeito Enxerto vs Leucemia/imunologia , Transfusão de Leucócitos/métodos , Antígenos de Neoplasias/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Humanos , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/métodos , Subpopulações de Linfócitos T/imunologia , Transplante Homólogo/efeitos adversos , Transplante Homólogo/imunologia , Transplante Homólogo/métodos
14.
Bone Marrow Transplant ; 27(11): 1215-7, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11551034

RESUMO

We report the case of a 46-year-old male who developed dermatomyositis and a sarcoid-like reaction in association with testicular relapse of multiple myeloma. The myositis progressed despite chemotherapy directed at the underlying malignant disorder and immunosuppressive treatment. There was, however, a dramatic and sustained response to high-dose chemotherapy and autologous peripheral blood stem cell transplantation which resulted in resolution of the myopathy and partial resolution of the sarcoid-like reaction. This case report highlights the potential of autologous stem cell transplantation as treatment for para-neoplastic disorders associated with haematological malignancies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dermatomiosite/terapia , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/complicações , Sarcoidose/terapia , Terapia Combinada , Dermatomiosite/diagnóstico , Dermatomiosite/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Recidiva , Sarcoidose/diagnóstico , Sarcoidose/etiologia , Neoplasias Testiculares/terapia , Resultado do Tratamento
15.
Bone Marrow Transplant ; 30(6): 401-4, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12235526

RESUMO

In common with other plasma cell dyscrasias in which a small tumour burden is associated with severe clinical symptoms (notably systemic AL amyloidosis) the possible benefits of dose intensification are yet to be fully explored in POEMS syndrome. One important issue is whether the toxicity of the procedure is significantly increased in this group. We report two cases of POEMS syndrome with solitary asymptomatic bone lesions treated with high-dose melphalan (200 mg/m(2)) and peripheral blood stem cell (PBSC) rescue. In both cases there was minimal peri-transplant morbidity and a subsequent substantial and maintained improvement in the peripheral neuropathy.


Assuntos
Síndrome POEMS/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/toxicidade , Pessoa de Meia-Idade , Síndrome POEMS/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
16.
Bone Marrow Transplant ; 25(6): 677-8, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10734304

RESUMO

We report a case of a 34-year-old man with T-ALL and beta-thalassaemia major who underwent a one antigen mismatched related donor bone marrow transplant. Five months post transplant chimeric studies revealed full donor haemopoiesis and the patient remains leukaemia and thalassaemia free at 12 months post transplant. Cumulative risk factors contributing to the increased transplant-related mortality in patients with two different marrow disorders are discussed.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas/efeitos adversos , Transplante de Medula Óssea/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Talassemia beta/terapia , Adulto , Doenças da Medula Óssea/imunologia , Doenças da Medula Óssea/terapia , Transplante de Medula Óssea/efeitos adversos , Intervalo Livre de Doença , Grécia/etnologia , Humanos , Isoantígenos/efeitos adversos , Masculino , Repetições de Microssatélites , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Fatores de Risco , Doadores de Tecidos , Quimeras de Transplante , Transplante Homólogo , Talassemia beta/complicações , Talassemia beta/imunologia
17.
Bone Marrow Transplant ; 24(7): 807-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10516687

RESUMO

We report a 45-year-old female with AML who underwent a T cell-depleted sibling allograft and relapsed a year later with extramedullary disease involving the lung parenchyma and presenting with the clinical and radiological features of interstitial pneumonitis. The patient was treated with donor lymphocyte infusion (DLI) resulting in complete resolution of the radiological signs. The unusual presentation and the management options are discussed.


Assuntos
Transplante de Medula Óssea , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/terapia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/terapia , Transfusão de Linfócitos , Transplante de Medula Óssea/patologia , Diagnóstico Diferencial , Feminino , Humanos , Leucemia Mieloide/patologia , Doenças Pulmonares Intersticiais/patologia , Transfusão de Linfócitos/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
18.
Bone Marrow Transplant ; 28(9): 827-34, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11781642

RESUMO

We evaluated the outcome of two modes of T cell depletion for HLA-identical sibling stem cell transplants in 34 consecutive adult patients: group A (n = 11) received PBSC post CliniMACs immuno-magnetic enrichment of CD34(+) cells and group B (n = 23) received bone marrow following in vitro incubation with CAMPATH-1M and complement. All patients received an identical conditioning regimen which consisted of in vivoCAMPATH-1H 20 mg over 5 days, thiotepa 10 mg/kg, cyclophosphamide 120 mg/kg and 14.4 Gy TBI. No additional graft-versus-host disease prophylaxis was given. The mean T cell dose administered was 0.02 +/- 0.05 x 10(6)/kg for group A and 2.8 +/- 2.8 10(6)/kg for group B (P < 0.001). With a median follow-up of 28 months overall survival was 36.4% for group A at 12 months compared to 78.3% for group B (P = 0.001). Transplant-related mortality in group A at 12 months was 63.6% as compared to 18.0% in group B (P = 0.003). Most of the procedure-related deaths in group A occurred secondary to infection. These results suggest that extensive in vitro T cell depletion of peripheral blood stem cells in combination with in vivo T cell depletion may have profound effects upon the incidence of infections following allogeneic stem cell transplantation and this may adversely effect transplant-related mortality.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Depleção Linfocítica/efeitos adversos , Linfócitos T , Adulto , Alemtuzumab , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Separação Imunomagnética , Incidência , Infecções/etiologia , Infecções/mortalidade , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Linfócitos T/imunologia , Linfócitos T/transplante , Transplante Homólogo , Resultado do Tratamento
19.
Leuk Lymphoma ; 43(3): 531-6, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12002756

RESUMO

Peripheral blood progenitor cells (PBPCs) have become the stem cell source of choice in autologous transplantation. In a prospective randomised trial, we previously demonstrated that autologous transplantation using filgrastim-mobilised PBPCs resulted in faster haematopoietic recovery with shorter hospitalisation and reduced platelet transfusions compared to bone marrow transplant (BMT). This study is a follow-up analysis evaluating the long-term clinical outcome. Seventy-two patients with advanced Hodgkin's disease or high-grade lymphoma were randomised to receive either filgrastim-mobilised PBPCs (n = 37) or bone marrow (n = 35) after BEAM chemotherapy. Fourteen patients withdrew from the study before commencing high-dose chemotherapy. Fourteen of the 58 patients who received treatment with chemotherapy and transplant have died, 6 (19%) in the ABMT arm and 8 (30%) in the PBPC transplant (PBPCT) arm. Twenty-five patients (81%) in the ABMT arm and 17 (63%) in the PBPCT arm, who received treatment, were in complete remission at the date of last follow-up. Progression-free survival and overall survival (OS) were similar for both arms (OS 81% at 46 months for ABMT versus 63% for PBPC; p = 0.38). Further prospective studies with larger number of patients need to be done to assess which source of stem cells may translate into a long-term clinical benefit for the patient.


Assuntos
Linfoma/mortalidade , Linfoma/terapia , Transplante de Células-Tronco/mortalidade , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Células Sanguíneas/transplante , Transplante de Medula Óssea , Intervalo Livre de Doença , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Transplante Autólogo/métodos , Transplante Autólogo/mortalidade
20.
Clin Exp Med ; 4(1): 1-9, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15598080

RESUMO

Imatinib mesylate represents the first of a new generation of molecularly targeted therapies engineered to disrupt signal transduction pathways. It is a tyrosine kinase inhibitor with relatively selective activity against the Abelson (ABL) proto-oncogene, platelet-derived growth factor receptor, and c-KIT receptor. Deregulated tyrosine kinase activity has been implicated as a central pathogenic event in a number of human malignancies, most notably chronic myeloid leukemia. In this myeloproliferative disorder the t(9;22) reciprocal translocation results in the generation of a novel fusion oncoprotein, BCR-ABL, with constitutive tyrosine kinase activity. Imatinib inhibits this activity, inducing remarkable rates of hematological and cytogenetic remission in excess of those seen with alternative medical therapies. Following a large phase III study comparing its efficacy with the combination of interferon alpha and low-dose cytarabine, it has emerged as the current gold standard therapy for patients with chronic-phase disease without a potential bone marrow donor and those considered unsuitable for bone marrow transplantation. Its integration into the management of those patients who might be considered for transplantation, which has historically been considered the only potentially curative approach, remains a major challenge. The increasing recognition and subsequent molecular characterization of resistance mechanisms has reinforced the need to exercise caution against deferring a proven curative therapy in favor of a treatment approach that is still investigational, with the spectre of increased numbers of patients progressing to sudden-onset blast crisis remaining the potential dark cloud in the silver lining for imatinib.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/economia , Benzamidas , Resistencia a Medicamentos Antineoplásicos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/economia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Piperazinas/efeitos adversos , Piperazinas/economia , Proto-Oncogene Mas , Pirimidinas/efeitos adversos , Pirimidinas/economia
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