RESUMO
The objective of this retrospective analysis was to compare outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who received either a matched sibling (sib) or an unrelated donor (URD) allogeneic hematopoietic cell transplantation (allo-HCT). Long-term outcome of 172 DLBCL patients receiving URD-HCT between 2000 and 2007 and reported to the European Group for Blood and Marrow Transplantation, was compared with that of 301 subjects, allografted from sib-HCT. With a median follow-up of 45 months, 3-year PFS approached 35% for both groups; overall survival (OS) was 42% for sib-HCT versus 37% for URD (NS). Multivariate analyses confirmed that donor type was not associated with differences in non-relapse mortality (NRM), relapse rate (RR), PFS or OS. Poor performance status (PS) and refractory disease adversely affected PFS and OS. Prior auto-SCT and multiple previous therapies predicted for shorter PFS. NRM was adversely affected by older age (⩾50 years), poor PS and refractory disease, and RR by time from diagnosis to allo-HCT of <36 months, prior auto-SCT, refractory disease, poor PS and in vivo T-cell depletion with alemtuzumab. This large study shows for the first time that URD-HCT is not inferior to sib-HCT, providing a reasonable therapeutic approach for DLBCL patients, having no HLA-identical sibling available.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/terapia , Adolescente , Adulto , Idoso , Criança , Progressão da Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Teste de Histocompatibilidade , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Estudos Retrospectivos , Irmãos , Transplante Autólogo , Transplante Homólogo , Doadores não Relacionados , Adulto JovemRESUMO
BACKGROUND: Limited experience is available on the feasibility and efficacy of autologous stem-cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) beyond 65 years. DESIGN AND METHODS: We analysed 712 patients with MCL treated with ASCT from 2000 to 2007 and reported to the European Group for Blood and Marrow Transplantation registry. Patients>65 years were compared with patients<65 years for the end points non-relapse mortality (NRM), relapse incidence, progression-free survival (PFS), and overall survival (OS). RESULTS: Seventy-nine patients were ≥65 years old. Median time from diagnosis to ASCT was longer in the elderly patients (11 versus 9 months, P=0.005); they had more commonly received at least two treatment lines (62.0% versus 47.9%, P=0.02) and were less commonly in first complete remission at ASCT (35.4% versus 51.2%, P=0.002). Median follow-up after ASCT was 19 and 25 months, respectively. NRM was comparable at 3 months (3.8% versus 2.5%) and at 5 years (5.6% versus 5.0%). There were no differences in relapse rate (66% versus 55% at 5 years), PFS (29% versus 40%) and OS (61% versus 67%) between both populations of patients. CONCLUSION: ASCT beyond 65 years of age is feasible in selected patients with MCL and results in similar disease control and survival as in younger patients.
Assuntos
Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/cirurgia , Transplante de Células-Tronco/mortalidade , Adulto , Distribuição por Idade , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Transplante AutólogoRESUMO
Many parameters predict for outcome after unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (alloSCT). High-resolution HLA-matching significantly impacts outcome and also the European Group of Blood and Marrow Transplantation (EBMT) risk score, based on patient age, disease stage, donor type, time from diagnosis to SCT and gender combination, may predict for non-relapse mortality and overall survival (OS). We evaluated the individual and combined effects of allele-matching and the EBMT risk score in 327 patients with poor-risk acute leukemia or myelodysplasia, who received a T-cell depleted URD alloSCT. Matching for HLA-A, -B, -C and -DRB1 alleles (8/8 match) was associated with a 5-year OS of 40% compared with 30% for mismatched (≤7/8) pairs (P=0.02). Patients with EBMT risk scores of 1-2, 3, 4 and 5-7 had 5-year OS estimates of 53, 43, 30 and 20%, respectively (P<0.001). The favorable prognostic impact of an 8/8 donor was most pronounced if the EBMT risk score was low (1-2). Five-year OS was 74±8% vs 39±11% for fully matched patients with a low-risk EBMT score as compared with EBMT low-risk patients with ≤7/8 donors. These data underscore the importance of incorporating both the EBMT risk score and the degree of high-resolution HLA-matching in the risk assessment prior to URD alloSCT.
Assuntos
Alelos , Transplante de Medula Óssea , Leucemia/cirurgia , Síndromes Mielodisplásicas/cirurgia , Linfócitos T/citologia , Doença Aguda , Adulto , Feminino , Teste de Histocompatibilidade , Humanos , Leucemia/genética , Masculino , Síndromes Mielodisplásicas/genética , Recidiva , RiscoRESUMO
Five patients with adult-onset metachromatic leukodystrophy (MLD) underwent allo-SCT. Conditioning was reduced in intensity and grafts were obtained from voluntary unrelated donors. All but one graft were depleted of T-lymphocytes. Patient age at transplantation varied from 18 to 29 (median, 27) years. Two patients rejected their graft and MLD progressed. The recipient of the unmanipulated graft converted to complete donor chimerism with normalization of arylsulphatase A (ARSA) levels. Despite ARSA normalization, he deteriorated. Another patient was a mixed chimera. Following escalated doses of donor lymphocyte infusions he converted to complete donor chimerism. His levels of ARSA correlated positively with the percentage of donor cells and MLD was not progressive. The fifth patient died after 35 days from complications associated with GVHD. We conclude that results of allo-SCT in symptomatic MLD patients are poor. However, allo-SCT may stop progression of MLD in selected patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucodistrofia Metacromática/cirurgia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: To describe activities in the field of autologous stem cell transplantation in haematological disorders in the Netherlands in the periods before and after 1993 (at that time blood was introduced as source of stem cells). DESIGN: Descriptive, retrospective cohort study. METHOD: Data were collected from the Netherlands Stem Cell Transplantation Registry TYPHON. Details of all transplant patients were reported to TYPHON by the individual transplantation centres. In this overview we describe the changes in transplantation-related mortality, relapse rates and survival in the periods 1 January 1980-31 December 1992 and 1 January 1980-31 December 2002. RESULTS: The number of autologous stem cell transplantations increased almost five-fold in the period 1993-2002. Since 1993 the main indications for transplantation were multiple myeloma (MM) and non-Hodgkin lymphoma (NHL), as well as acute myeloid leukaemia (AML), which was the main indication in the period before 1993. In the period before 1993 most relapses were observed in patients with acute lymphoblastic leukaemia (ALL) and MM, which resulted in low survival rates. After 1993 no great differences in relapse or survival rates were observed between the different disorders. The survival rates for patients with ALL improved during the last research period, especially among younger patients (< 45 years). CONCLUSION: The number of autologous stem cell transplantations has increased considerably since 1993, especially in patients with MM and NHL.
Assuntos
Doenças Hematológicas/mortalidade , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Adulto JovemRESUMO
Natural killer (NK) cells have an important function in the anti-tumor response early after stem cell transplantation (SCT). As part of a prospective randomized phase III study, directly comparing the use of CD3(+)/CD19(+)-depleted peripheral blood stem cell (PBSC) harvests with CD34(+)-selected PBSC harvests in allogeneic human leukocyte antigen-matched SCT, we here show that the use of CD3(+)/CD19(+)-depleted PBSC grafts leads to early NK cell repopulation and reconstitution of the CD56(dim) and CD56(bright) NK cell subsets, with concomitant high cytolytic capacity. In the CD34 group, this process took significantly longer. Moreover, in the CD3/19 group after reconstitution, a higher percentage of killer immunoglobulin-like receptor-positive NK cells was found. Although similar percentages of CD94-positive NK cells were found in both groups, in the CD34 group, almost all expressed the inhibitory CD94:NKG2A complex, whereas in the CD3/19 group, the inhibitory CD94:NKG2A and the activating CD94:NKG2C complex were equally distributed. This preferential development of NKG2C-expressing NK cells in the CD3/19 group was paralleled by a loss of NKG2A-mediated inhibition of NK cell degranulation. These results show that the use of CD3(+)/CD19(+)-depleted grafts facilitates strong NK cell cytolytic responses directly after SCT, and the rapid emergence of an NK cell receptor phenotype that is more prone to activation.
Assuntos
Antígenos CD19/análise , Complexo CD3/análise , Teste de Histocompatibilidade , Células Matadoras Naturais/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/fisiologia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Idoso , Antígeno CD56/análise , Citotoxicidade Imunológica , Humanos , Leucemia/terapia , Pessoa de Meia-Idade , Subfamília D de Receptores Semelhantes a Lectina de Células NK/análise , Estudos Prospectivos , Transplante HomólogoRESUMO
We studied GVHD after donor lymphocyte infusion (DLI) in 328 patients with relapsed CML between 1991 and 2004 . A total of 122 patients (38%) developed some form of GVHD. We analyzed GVHD by clinical presentation (acute or chronic GVHD) and onset time after the first DLI (early (< or =45 days) or late (>45 days)). There was a significant overlap between onset time and clinical presentation. Some form of GVHD occurred at a median of 104 days, acute GVHD at 45 days and chronic GVHD at 181 days after DLI. The clinical presentation was acute GVHD in 71 patients, of whom 31 subsequently developed chronic GVHD subsequently. De novo chronic GVHD was seen in 51 patients. OS for all patients was 69% (95% confidence interval (CI) 63-75) at 5 years, DLI-related mortality was 11% (95% CI 8-15) and disease-related mortality was 20% (95% CI 16-25). Risk factors for developing GVHD after DLI were T-cell dose at first DLI, the time interval from transplant to DLI and donor type. In time-dependent multivariate analysis, GVHD after DLI was associated with a risk of death of 2.3-fold compared with patients without GVHD. Clinical presentation as acute GVHD and early onset GVHD were associated with increased mortality.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Linfócitos/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Recidiva , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemAssuntos
Leucemia/terapia , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/estatística & dados numéricos , Doadores de Tecidos , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos/estatística & dados numéricos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
The aim of the study was to evaluate the clinical performance of two different one-step self-etching adhesives (Hybrid Bond/Sun Medical, Xeno III/Dentsply) in adhesive cervical resin composite restorations. In accordance with a split-mouth study design, 50 patients (57.3+/-13.5) received at least one pair of restorations. In each of two comparable cervical cavities, either the adhesive systems Hybrid Bond or Xeno III was used with the resin composite Filtek Supreme (3M ESPE). After 6, 12 and 24 months, the restorations were scored according to the Ryge and California Dental Association criteria. After 2 years, the resulting scores (percent) of the Ryge evaluation for the groups Hybrid Bond/ Filtek Supreme and Xeno III/ Filtek Supreme were marginal integrity, Alpha (92/78), Bravo (8/2), Charlie (0/0) and Delta (0/10); anatomic form, Alpha (92/82), Bravo (8/8) and Charlie (0/10); secondary caries, Alpha (100/100) and Bravo (0/0); marginal discoloration, Alpha (80/84), Bravo (20/12), Charlie (0/0) and not available (0/4); color match, Oscar (39/47), Alpha (51/45), Bravo (10/4), Charlie (0/0) and not available (0/4); surface, Romeo (78/69), Sierra (22/22), Tango (0/0) and Victor (0/10); tooth vitality, Alpha (98/94), Bravo (2/6); and integrity of tooth, alpha 1 (96/96) and alpha 2 (4/4). After 2 years, all Hybrid Bond restorations were retained and showed clinically acceptable results, while five Xeno III restorations were lost in part or in toto. For marginal integrity, anatomic form and surface, significant differences (p<0.05) were found but did not prove statistically significant after Bonferroni adjustment.
Assuntos
Resinas Compostas , Restauração Dentária Permanente/métodos , Adesivos Dentinários , Cimentos de Resina , Autocura de Resinas Dentárias , Colo do Dente , Corrosão Dentária/métodos , Falha de Restauração Dentária , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
OBJECTIVE: Systemic sclerosis (SSc) is a generalised autoimmune disease, causing morbidity and a reduced life expectancy, especially in patients with rapidly progressive diffuse cutaneous SSc. As no proven treatment exists, autologous haematopoietic stem cell transplantation (HSCT) is employed as a new therapeutic strategy in patients with a poor prognosis. This study reports the effects on survival, skin and major organ function of HSCT in patients with severe diffuse cutaneous SSc. PATIENTS AND METHODS: A total of 26 patients were evaluated. Peripheral blood stem cells were collected using cyclophosphamide (4 g/m2) and rHu G-CSF (5 to 10 microg/kg/day) and were reinfused after positive CD34+ selection. For conditioning, cyclophosphamide 200 mg/kg was used. RESULTS: After a median follow-up of 5.3 (1-7.5) years, 81% (n = 21/26) of the patients demonstrated a clinically beneficial response. The Kaplan-Meier estimated survival at 5 years was 96.2% (95% CI 89-100%) and at 7 years 84.8% (95% CI 70.2-100%) and event-free survival, defined as survival without mortality, relapse or progression of SSc, resulting in major organ dysfunction was 64.3% (95% CI 47.9-86%) at 5 years and 57.1% (95% CI 39.3-83%) at 7 years. CONCLUSION: This study confirms that autologous HSCT in selected patients with severe diffuse cutaneous SSc results in sustained improvement of skin thickening and stabilisation of organ function up to 7 years after transplantation.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Escleroderma Sistêmico/terapia , Adolescente , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Morbidade , Agonistas Mieloablativos/uso terapêutico , Proteínas Recombinantes , Escleroderma Sistêmico/mortalidade , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante AutólogoRESUMO
Donor lymphocyte infusion (DLI) after allogeneic SCT induces complete remissions in approximately 80% of patients with relapsed CML in chronic phase, but some patients do not respond to DLI. We studied absolute numbers of dendritic cell (DC) subsets and chimerism in T cells and two subsets of blood DCs (myeloid DCs (MDCs) and plasmacytoid DCs (PDCs)) in relation to DLI-induced alloreactivity. Based on T cell and DC chimerism, we identified three groups. Four patients were completely donor chimeric in T cells and DC subsets. These patients had an early stage of relapse, and three of the four patients attained complete molecular remission (CMolR) without significant GVHD. Six patients were completely donor in T cells and mixed chimeric in DC subsets. All patients entered CMolR, but this was associated with GVHD in four and cytopenia in three patients. Five patients had mixed chimerism in T cells and complete recipient chimerism in MDC; only two patients entered CMolR. Our data suggest that the combination of donor T cells and mixed chimerism in DC subsets induces a potent graft-versus-leukemia (GVL) effect in association with GVHD. DLI in patients with an early relapse and donor chimerism in both T cells and DC subsets results in GVL reactivity without GVHD.
Assuntos
Células Dendríticas/imunologia , Efeito Enxerto vs Leucemia/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Linfócitos , Linfócitos T/imunologia , Quimeras de Transplante/imunologia , Adulto , Idoso , Doadores de Sangue , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de RemissãoRESUMO
The purpose of this study was to determine the role of pre-emptive donor lymphocyte infusion (pDLI) after partial T-cell-depleted allogeneic SCT in patients with multiple myeloma (MM). A cohort of 24 MM patients was treated with partial T-cell-depleted myeloablative SCT between December 1997 and April 2002. These patients were intended to receive pDLI after SCT. The overall response rate after SCT was 83% (20 of 24 patients) with 10 patients (42%) in complete remission (CR). Transplant-related mortality within 1 year after SCT was 29%. Thirteen patients (54%) received pDLI and four patients in partial remission reached CR. GVHD>grade I after pDLI developed in 4 out of 13 patients (30%). Four patients received therapeutic DLI, without preceding pDLI. Eleven patients (46%) are alive, with a median follow-up of 67 months (range, 48-100 months). Seven of these patients (29%) are in continuous CR (CCR), which was confirmed by a negative patient-specific IgH PCR in four patients. All seven patients in CCR received pDLI. Although myeloablative SCT in MM induces high toxicity, we show that the concept of T-cell depletion followed by pDLI is promising and needs to be investigated in a reduced-intensity conditioning setting.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Depleção Linfocítica , Mieloma Múltiplo/terapia , Linfócitos T/transplante , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quimeras de Transplante , Condicionamento Pré-Transplante/métodos , Transplante HomólogoRESUMO
The literature suggests that cancer survivors with more aggressive treatments are more at risk for postcancer fatigue. In this study, we investigated the prevalence of fatigue after completion of stem cell transplantation (SCT). Furthermore, we studied if medical variables are associated with fatigue and if the model of perpetuating factors of postcancer fatigue derived from previous studies in cancer survivors, without SCT, is applicable in SCT survivors. Ninety-eight patients treated with autologous or allogeneic SCT filled out several questionnaires. Medical characteristics were obtained from the medical charts. All patients had to be in persistent complete remission for at least 1 year. Thirty-five per cent of the patients experienced severe fatigue. The percentage of patients with severe fatigue remained stable during the years after transplantation. Several psychosocial factors, but no medical factors, were associated with fatigue. The model of perpetuating factors appeared to be applicable. Contrary to cancer survivors without SCT, we found no decrease in fatigue complaints during the first years after SCT. Cognitive behaviour therapy (CBT) is a general form of psychotherapy directed at changing condition-related cognitions and behaviours. CBT especially designed for postcancer fatigue, aimed at perpetuating factors, can also be used to manage fatigue in cancer survivors treated with SCT.
Assuntos
Fadiga/etiologia , Transplante de Células-Tronco/efeitos adversos , Adulto , Idoso , Terapia Cognitivo-Comportamental , Fadiga/psicologia , Fadiga/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Neoplasias/terapia , Países Baixos , Psicologia , Fatores de Risco , Transplante de Células-Tronco/psicologia , Inquéritos e Questionários , Fatores de Tempo , Transplante Autólogo , Transplante HomólogoRESUMO
A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase entered the study. Twenty-eight out of 32 patients assigned to group A received two cycles of a combination of intensified cytarabine and idarubicin followed by interferon alfa (IFN-alpha) maintenance, 28 patients in group B received standard treatment by a combination of low-dose cytarabine and IFN-alpha. Forty-nine patients with a human leukocyte antigen-identical sibling donor proceeded to allogeneic stem cell transplantation (allo-SCT) and nine patients were excluded from the analysis. Hematological response was observed in 97% of the patients in group A vs 86% of the patients in group B during the first year of treatment. In group A, 16 patients (50%) achieved a major cytogenetic response, which compared to seven patients (25%) with a major cytogenetic response in group B. With a median follow-up of 58 months (range 34-76), event-free survival was not significantly different between arms A and B. The estimated 5-year survival rate was 56% in the intensified arm and 77% in the low-dose arm (P = 0.05). Recipients of allo-SCT showed a 5-year estimated survival rate of 55%. Although intensified cytarabine induced a higher initial percentage of major and complete cytogenetic responses, responses were not sustained by IFN-alpha maintenance therapy.
Assuntos
Citarabina/uso terapêutico , Interferon-alfa/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/patologia , Adolescente , Adulto , Idoso , Citarabina/administração & dosagem , Citogenética , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Interferon-alfa/efeitos adversos , Leucemia Mieloide de Fase Crônica/genética , Leucemia Mieloide de Fase Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco , Taxa de Sobrevida , Transplante HomólogoRESUMO
In the Netherlands, the practice of private freezing and banking of umbilical-cord blood is increasing. In a questionnaire, Dutch midwives and gynaecologists were asked about their attitude towards cord-blood collection if asked to perform this after delivery. The response rate was 35% (125/356) and 71% (71/100), respectively. Two-thirds of those asked responded that they would comply. The most common application of cord blood is in the treatment of (malignant) blood disorders. The use of autologous cord blood is, however, often not the best choice for treating leukaemia in young children and the number of stem cells is often too low in a single-cord blood sample to treat older children and adults. Although frequently suggested in the lay press, there is no proven effect in other indications, such as amyotrophic lateral sclerosis, multiple sclerosis and myocardial infarction. Information on therapeutic applications of cord blood from companies with commercial interests is leading to the exploitation ofpregnantwomen. The government should consider limiting this practice and prohibiting the activities of these companies in the Netherlands pending scientific evidence for their claims.
Assuntos
Células da Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Sangue Fetal , Conhecimentos, Atitudes e Prática em Saúde , Gestantes/psicologia , Bancos de Sangue , Feminino , Neoplasias Hematológicas/terapia , Histocompatibilidade , Humanos , Países Baixos , Gravidez , Coleta de Tecidos e Órgãos , Transplante AutólogoRESUMO
Blood concentrations of cyclosporine A (CsA) >or=800 microg/l measured 2 h post-dosing, the C2 concentration, is necessary to obtain a maximal pharmacological effect and correlates well with transplant-related complications such as transplant rejection and toxicity. In an open crossover study CsA blood levels were measured during 24 h to generate a pharmacokinetic profile on days 1, 8 and 15 after starting CsA infusion in 21 haematopoietic allogeneic stem cell transplant recipients who were receiving intravenously CsA 3 mg/kg/day either by continuous infusion or by 2 h infusion given every 12 h. C2 levels after the 2 h infusion correlated better than C1 or C3 levels with the area under the concentration-time curve from 0 to 4 h (r2=0.62). C2 levels >or=800 microg/l were also achieved for 20 out of 24 (83%) of cases after the 2 h infusion of CsA without any increase of CsA-related toxicity but for only three of the 23 patients (13%) after continuous infusion. Therefore, we recommend CsA infusions in 2 h during transplant and perform C2 monitoring to obtain therapeutic C2 levels >or=800 microg/l.
Assuntos
Ciclosporina/farmacocinética , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/farmacocinética , Adulto , Distribuição de Qui-Quadrado , Estudos Cross-Over , Ciclosporina/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Transplante HomólogoRESUMO
Thirty-four men and 36 women (median age 43 and 45 years, respectively) underwent stem cell transplantation (SCT) for acute leukaemia in first complete remission or chronic myelogenous leukaemia in first chronic phase between 1981 and 2001 from HLA-identical siblings. The conditioning regimen included TBI and all grafts were partially depleted of T cells. Changes in quality of life (QOL), reproduction and sexuality were studied using a questionnaire, and the previously given information related to these problems was assessed. In addition, endocrine status was assessed and semen analysis was performed. After SCT, patients reported less energy (n=50) and a deterioration in the job situation (n=31). Patients experienced a negative change in sexual relations (n=41). Important problems of sexual dysfunction were vaginal dryness in women (n=19) and erectile dysfunction in men (n=16). None of the patients was fertile based on their gonadotrophin levels, sperm concentrations and reproductive outcomes. Women experienced climacteric symptoms (n=24). Quality of life was negatively influenced by these changes. One-fifth of the patients were not satisfied with the information given with regard to reproduction, premature menopause and sexual problems.
Assuntos
Depleção Linfocítica , Qualidade de Vida , Sexualidade , Transplante de Células-Tronco/psicologia , Linfócitos T/imunologia , Adulto , Terapia Combinada , Família , Feminino , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Seleção de Pacientes , Sêmen/fisiologia , Inquéritos e Questionários , Irradiação Corporal TotalRESUMO
We conducted a prospective, randomised, double-blinded, placebo-controlled pilot study of parenteral nutrition (PN) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant (SCT) recipients to determine its effect on mucosal barrier injury (MBI). All patients had been prepared with idarubicin, cyclophosphamide and total body irradiation. PN (by continuous infusion) started on SCT day -6 for a median of 19 days. MBI measured by sugar permeability tests, daily mucositis score, daily gut score, and citrulline concentrations was not reduced by glutamine-dipeptide. However, the daily gut score was significantly lower for the glutamine group on SCT +7 (p = 0.001) whilst citrulline was lower (p = 0.03) for the placebo group on SCT day +21. Albumin was significantly lower in the placebo group on SCT day +21 (32+/-4 versus 37+/-3, p = 0.001) whilst CRP was higher (74+/-48 versus 34+/-38, p = 0.003). Other transplant-related complications (infections, acute graft-versus-host disease) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality. These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications.
Assuntos
Glutamina/administração & dosagem , Transplante de Células-Tronco , Transplante Homólogo , Adolescente , Adulto , Método Duplo-Cego , Feminino , Glutamina/uso terapêutico , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Países Baixos , Projetos Piloto , PlacebosRESUMO
The impact of the donor gender on outcome in HLA-identical sibling donor hematopoietic stem cell transplantation for multiple myeloma was studied in a retrospective registry study of 1312 patients (476 male to male (M --> M); 334 female to male (F --> M); 258 male to female (M --> F); 244 female to female (F --> F) reported to the European Group for Blood and Marrow Transplantation (EBMT). The best overall survival (OS) from the time of transplantation was found in F --> F (median 41 months) with no significant difference between other groups (median 25 months in M --> M, 18 months in F --> M, 19 months in M --> F) despite a significantly higher nonrelapse mortality in F --> M. This was due to a significantly lower relapse rate (REL) in F --> M compared to all other groups. Before 1994, OS was poorer in F --> M than in M --> M, which improved to similarity from 1994 onwards (median 29 months in M --> M and 25 months in F --> M). The reduced REL contributed to this improvement in F --> M indicting a gender-specific graft vs myeloma effect. Therefore, a female donor is as good as a male one for male patients, while for female patients gender disparity is a negative factor for outcome.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Doadores de Tecidos , Adulto , Feminino , Efeito Enxerto vs Tumor , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Risco , Fatores Sexuais , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
OBJECTIVE: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. METHODS: Only patients with SSc, treated by HSCT in European phase I-II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). RESULTS: Given as median (range). Among 57 patients aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5-81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). CONCLUSION: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.