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1.
Biol Blood Marrow Transplant ; 17(1): 133-40, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20601032

RESUMO

Although imatinib has become standard first-line therapy in chronic myelogenous leukemia (CML), allogeneic hematopoietic stem cell transplantation (HSCT) is still considered to be an important treatment alternative for patients with drug resistance or advanced disease. We retrospectively analyzed 175 adult CML patients who underwent HSCT at our institution between 1983 and 2007, with the aim to compare outcomes in patient subgroups and to identify prognostic variables. The median follow-up was 65 months. The probability of overall survival (OS) for all patients was 62%, with a significant improvement seen in the imatinib-era (2001-2007) compared to previous time periods (P <.05). Furthermore, a significantly better outcome for patients with chronic phase CML compared to patients with accelerated or blast phase could be observed (P < .05). Cumulative incidence (CI) of treatment-related mortality (TRM) was 9.7% at 100 days and 1 year after HSCT. CI of relapse was 5% at 1 year and 7.5% at 3 years after HSCT. Post-HSCT outcome was not influenced by pretreatment therapy with imatinib, donor type, or a conditioning regimen with total body irradiation (TBI). These data confirm earlier observations and suggest that allogeneic HSCT is still an important treatment option for high-risk patients with CML, and should thus remain an integral component in current and future treatment algorithms.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/tendências , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adulto , Benzamidas , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Prognóstico , Pirimidinas/uso terapêutico , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
2.
Transfus Med Hemother ; 38(5): 292-299, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22670118

RESUMO

BACKGROUND: The Austrian Bone Marrow Donor Registry is the central search coordinating unit in charge of national and international donor searches in Austria. PATIENTS AND METHODS: Between 1988 and 2010, a worldwide search for an unrelated donor of blood stem cells (URD) was initiated for 2,166 Austrian patients with haematological disorders, 1,671 adults and 495 children, by the Austrian Bone Marrow Donor Registry. RESULTS: An URD was identified for 78.3% of the patients between 2008 and 2010, for 76.7% of the patients between 2004 and 2007, for 71.3% between 1996 and 2003, but only for 53.4% of the patients in the initial period of 1988-1995. Thus, results of international donor searches improve over time. In contrast, search duration decreases steadily: Search times of successful searches decreased from about 8 months in the first period between 1988 and 1996 to 1.84 months in 2010. Overall, 1,558 of the 2,166 patients (71.9%) could be provided with a matching donor. However, not every patient provided with a URD was transplanted. Overall, only 1,141 of 2,166 patients (52.7%) proceeded to transplant. CONCLUSION: Figures have significantly improved for the latest period of donor searches between 2008 and 2010. In this period, a donor could be found for 78.3%, and 58.5% of the patients received a transplant.

3.
Biol Blood Marrow Transplant ; 15(11): 1400-6, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19822299

RESUMO

We investigated the impact of ABO and Rhesus (Rh) blood group matching on the outcome of hematopoietic stem cell transplantation (HSCT) of 154 patients matched at 10/10 HLA loci with unrelated donors. ABO and Rh, as potential risk factors, were modeled with the clinical outcome--acute and chronic graft-versus-host disease (aGVHD, cGVHD), relapse, treatment-related mortality (TRM), and overall survival (OS)--by simple, multiple, and competing risk analyses. We found that minor ABO-mismatches represent a significant risk factor for aGVHD (II-IV) with an estimated risk increase of almost 3-fold (hazard ratio [HR]=2.92, 95% confidence interval [CI]: 1.43-5.95, P=.003), and even 4-fold for aGVHD (III-IV) (HR=4.24, 95% CI: 1.70-10.56, P=.002), but not for other transplant endpoints. No significant association of the Rh matching status with any of the HSCT endpoints was seen. These results suggest that ABO minor mismatches may play a role in aGvHD pathophysiology, possibly by providing the setting for T cell activation and antibody mediated damage. To decrease the risk of aGVHD, ABO matching should be considered in HSCT.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/complicações , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Adolescente , Adulto , Doenças da Medula Óssea/cirurgia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Antígenos HLA/imunologia , Humanos , Leucemia/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
4.
Br J Haematol ; 142(3): 436-43, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18544086

RESUMO

The interpretation of the role of HLA-DPB1 in unrelated haematopoietic stem cell transplantation (HSCT) is subject to discussion. We have investigated the role of HLA-DPB1 allele matching in HSCT outcomes in 161 recipients who were HLA-A, -B, -C, -DRB1 and -DQB1-matched with their unrelated donors at the allelic level (10/10). In addition, we analysed the association of polymorphic amino acid mismatches of DPB1 molecule with HSCT end-points, and a previously published permissiveness concept. HLA-DPB1 allele mismatches were significantly associated with an increased incidence of acute graft-versus-host disease (aGvHD) and worse overall survival (OS). The mismatch at amino acid position 69 significantly increased the risk for transplant-related mortality (TRM). Risk factors for aGvHD also included mismatches at positions 8, 9, 35, 76 and 84. This is to our knowledge, the first report of an in vivo effect of single amino acid mismatches on HSCT outcomes. In this study, grouping of allelic mismatches into permissive and non-permissive categories and their association with transplantation end-points was relevant for TRM but not for other clinical end-points.


Assuntos
Aminoácidos/genética , Antígenos HLA-DP/genética , Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Polimorfismo Genético , Doença Aguda , Adolescente , Adulto , Alelos , Doença Crônica , Feminino , Seguimentos , Frequência do Gene , Doença Enxerto-Hospedeiro , Antígenos HLA-DP/imunologia , Cadeias beta de HLA-DP , Transplante de Células-Tronco Hematopoéticas/mortalidade , Teste de Histocompatibilidade/métodos , Humanos , Leucemia/imunologia , Leucemia/mortalidade , Leucemia Mieloide/imunologia , Leucemia Mieloide/mortalidade , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Taxa de Sobrevida , Adulto Jovem
5.
Haematologica ; 90(10): 1405-14, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16219578

RESUMO

BACKGROUND AND OBJECTIVES: Anti-thymocyte globulin (ATG) is given in various conditioning regimens for children and young adults undergoing hematopoietic stem cell transplantation (HSCT) from HLA non-identical donors in order to reduce the risks of graft-versus-host disease (GvHD) and rejection after the transplant. The aim of this study was to define the effect of in vitro T-cell depletion in addition to ATG on the reconstitution of T-cell-mediated immunity. DESIGN AND METHODS: We retrospectively analyzed the engraftment kinetics and clinical performance of 134 patients (median age 5.80 years) who received ATG during myeloablative or reduced intensity conditioning, and either in vitro T-cell-depleted or unmanipulated grafts. RESULTS: T-cell reconstitution was significantly delayed after T-cell-depleted grafts, irrespectively of the conditioning intensity (p<0.001). The incidence of fatal viral and fungal infections was higher in recipients of T-cell-depleted grafts than in those receiving unmanipulated grafts (26.6-29% versus

Assuntos
Soro Antilinfocitário/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Depleção Linfocítica , Linfócitos T/imunologia , Linfócitos T/metabolismo , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos
6.
Transfusion ; 47(8): 1494-502, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17655594

RESUMO

BACKGROUND: Delayed severe immune hemolysis due to donor-derived passenger lymphocytes is observed in minor and/or bidirectional ABO-mismatched transplants, especially after reduced-intensity conditioning (RIC). The incidence is reported in up to 30 percent of patients and can result in multiorgan failure (MOF) and death. STUDY DESIGN AND METHODS: A first group of 32 patients (historical control) underwent RIC followed by allogeneic hematopoietic peripheral blood progenitor cell transplantation at our institution. In 5 of 10 patients with a minor and/or bidirectional ABO-mismatched graft, severe immune hemolysis was observed, leading to death in 3 of them. Therefore, we initiated a protocol with prophylactic red blood cell (RBC) exchange in minor and/or bidirectional ABO mismatch of a second group of patients (study group) and investigated the incidence of hemolysis, transplant-related mortality (TRM), and overall survival (OS) and compared these data with the historical control group. Twenty-two of 80 patients in the study group had a minor and/or bidirectional ABO-mismatched donor. RESULTS: In 20 patients, a prophylactic RBC exchange was performed. Three patients showed mild to moderate citrate reactions, and in 1 patient the procedure had to be stopped because of hypotension. Eighteen of 20 patients engrafted uneventfully, 1 patient rejected his graft, and another 1 showed signs of mild hemolysis. In the minor and/or bidirectional ABO-mismatched setting patients in the study group had a lower risk for TRM at 1 year compared to patients in the historical control group (16% vs. 53%, p < 0.05) and a better 1-year OS (65% vs. 40%, p < 0.05). CONCLUSION: RBC exchange is a safe procedure, reducing the incidence of delayed severe immune hemolysis and thus the risk of TRM in minor and/or bidirectional ABO-mismatched cases.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/sangue , Transfusão de Eritrócitos , Transfusão Total , Hemólise , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Transplante Homólogo
7.
J Pediatr Hematol Oncol ; 27(10): 532-6, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16217256

RESUMO

To analyze the dose effects of rabbit-derived antithymocyte globulin (ATG) in children after allogeneic hematopoietic stem cell transplantation (HSCT), ATG serum levels were monitored in 32 children and adolescents (median age 3.42 years, range 0.34-18.67 years) and the incidence of acute and chronic graft-versus-host disease, rejection, viral infections, EBV-lymphoproliferative disease, and survival was correlated with the ATG dose used. Cumulative doses from 7.5 to 20 mg/kg showed a constant half-life and linear correlation between dose and Cmax, whereas higher doses (30-40 mg/kg) accumulated in the body. High-dose ATG is of no benefit for preventing graft-versus-host disease but is associated with a significant increase in EBV-linked disease, and it appears to enhance the susceptibility to fatal viral infections and rejection. These data strongly support the use of a low-dose ATG regimen in pediatric HSCT.


Assuntos
Soro Antilinfocitário/sangue , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/sangue , Transtornos Linfoproliferativos/patologia , Adolescente , Animais , Soro Antilinfocitário/administração & dosagem , Criança , Pré-Escolar , Ciclosporina/farmacologia , Relação Dose-Resposta a Droga , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/patologia , Feminino , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Herpesvirus Humano 4/isolamento & purificação , Teste de Histocompatibilidade , Humanos , Imunossupressores/administração & dosagem , Incidência , Lactente , Transtornos Linfoproliferativos/etiologia , Masculino , Coelhos , Estudos Retrospectivos , Condicionamento Pré-Transplante
9.
Br J Haematol ; 117(4): 914-23, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12060131

RESUMO

Between 1982 and 2000, 172 patients with acute myelogenous leukaemia (AML) received haematopoietic stem cell transplants (SCT) from related (n = 132) or unrelated (n = 40) donors at four Austrian transplant centres and their results were reported to the Austrian Stem Cell Transplantation Registry. Conditioning for SCT consisted of cyclophosphamide and total body irradiation in 156 (91%) patients. Graft-versus-host disease (GVHD) prophylaxis was with standard cyclosporine and methotrexate in 95 (55%) patients. Median post-transplant follow-up was 5.6 years (range, 0.2--16.7). Multivariate analysis of transplant-related mortality (TRM) identified four variables associated with a lower risk: disease status of first complete remission (CR) at SCT, patient age of 45 years and younger, transplant performed during or after 1995, and lack of acute GVHD. Variables associated with significantly improved leukaemia-free survival were: bone marrow as the stem cell source, disease status of first CR at SCT, and occurrence of chronic GVHD. In multivariate analysis, transplantation performed during or after 1995, first CR at SCT, occurrence of limited chronic GVHD and lack of acute GVHD grades III to IV were associated with increased overall survival. Based on these analyses, options for the improvement of results obtained with allogeneic SCT in patients with AML could be defined.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/cirurgia , Adulto , Fatores Etários , Ciclosporina/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Metotrexato/uso terapêutico , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Irradiação Corporal Total
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