RESUMO
BACKGROUND: We conducted a retrospective survey within the European Society for Blood and Marrow Transplantation (EBMT) registry to assess the outcomes of cord blood transplantation (CBT) in secondary acute myeloid leukaemia (sAML). METHODS: Inclusion criteria consisted of ≥18 years of age, sAML, first CBT between 2002 and 2016, and either first complete remission (CR) or active disease at CBT. RESULTS: One hundred forty-six patients met the study inclusion criteria. Status at transplantation was first CR (n = 97), primary refractory sAML (n = 30) or relapsed (n = 19) sAML. Neutrophil engraftment was achieved in 118 patients while the remaining 25 patients (17%) failed to engraft. This includes 13% of patients transplanted in first CR versus 30% of those transplanted with active disease (P = 0.008). Two-year incidences of relapse were 25% in first CR patients versus 36% in those with advanced disease (P = 0.06) while 2-year incidences of nonrelapse mortality were 35% and 49% (P = 0.03), respectively. At 2-year overall survival, leukaemia-free survival and graft-versus-host disease (GVHD)-free relapse-free survival were 42% vs. 19% (P < 0.001), 40% vs. 16% (P < 0.001), and 26% vs. 12% (P = 0.002) in first CR patients versus those with advanced disease, respectively. CONCLUSIONS: We report here the first study of CBT in a large cohort of sAML patients. Main observation was that CBT rescued approximately 40% of patients with sAML in first CR.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation. METHODS: Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate. RESULTS: The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. CONCLUSIONS: The occurrence of grade II-IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Adulto JovemRESUMO
The EBMT risk score is an established tool successfully used in the prognosis of survival post-HSCT and is applicable for a range of haematological disorders. One of its main advantages is that score generation involves summation of clinical parameters that are available pretransplant. However, the EBMT risk score is recognized as not being optimal. Previous analyses, involving patients with various diagnoses, have shown that non-HLA gene polymorphisms influence outcome after allogeneic HSCT. This study is novel as it focuses only on patients having acute leukaemia (N = 458) and attempts to demonstrate how non-HLA gene polymorphisms can be added to the EBMT risk score in a Cox regression model to improve prognostic ability for overall survival. The results of the study found that three genetic factors improved EBMT risk score. The presence of MAL (rs8177374) allele T in the patient, absence of glucocorticoid receptor haplotype (consisting of rs6198, rs33389 and rs33388) ACT in the patient and absence of heat-shock protein 70-hom (+2437) (rs2227956) allele C in the patient were associated with decreased survival time. When compared to the EBMT risk score, the scores combining EBMT risk score with the genetic factors had an improved correlation with clinical outcome and better separation of risk groups. A bootstrapping technique, involving repeated testing of a model using multiple validation sets, also revealed that the newly proposed model had improved predictive value when compared to the EBMT risk score alone. Results support the view that non-HLA polymorphisms could be useful for pretransplant clinical assessment and provide evidence that polymorphisms in the recipient genotype may influence incoming donor cells, suppressing the initiation of the graft versus leukaemia effect and reducing survival.
Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia/genética , Leucemia/imunologia , Adulto , Feminino , Genômica , Genótipo , Proteínas de Choque Térmico HSP70/genética , Haplótipos/genética , Teste de Histocompatibilidade , Humanos , Leucemia/patologia , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Transplante Homólogo/efeitos adversosRESUMO
Double unrelated cord blood transplant (dUCBT) has been used to circumvent cell dose limitation of single UCBT; however, few data are available describing outcomes, infectious disease, and immune recovery. We analyzed 35 consecutive dUCBT recipients with high-risk malignant disorders (n=21) and bone marrow failure syndromes (n=14). Median follow-up was 32 months. Conditioning regimen was myeloablative in 14 and reduced intensity in 21 patients. Median infused nucleated cell dose was 4 × 10(7) /kg. Median time to absolute neutrophil count >0.5 × 10(9) /L was 25 days. Cumulative incidence (CI) of acute grade II-IV graft-versus-host disease was 47%. Estimated overall survival at 2 years was 48%. CI of first viral infections at 1 year was 92%. We observed 49 viral infections in 30 patients, 34 bacterial infections in 19 patients, and 16 fungal or parasitic infections in 12 patients. Lymphocyte subset analyses were performed at 3, 6, 9, and >12 months after dUCBT. Decreased T-cell and B-cell counts with expansion of natural killer cells were observed until 9 months post transplantation. Recovery of thymopoiesis measured by T-cell receptor excision circles was impaired until 9 months after dUCBT, when the appearance of new thymic precursors was observed. Delayed immune recovery and high incidence of infectious complications were observed after dUCBT in patients with high-risk hematological diseases.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Síndrome Inflamatória da Reconstituição Imune/patologia , Adolescente , Adulto , Anemia Aplástica , Infecções Bacterianas/etiologia , Doenças da Medula Óssea , Transtornos da Insuficiência da Medula Óssea , Criança , Feminino , Hemoglobinúria Paroxística/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Neoplasias/terapia , Doenças Parasitárias/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Viroses/etiologia , Adulto JovemRESUMO
The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.
Assuntos
Transplante de Medula Óssea/métodos , Países em Desenvolvimento/estatística & dados numéricos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Humanos , Fatores SocioeconômicosRESUMO
Patients with bone marrow failure syndromes (BMFS) who reject a first allogeneic transplant or fail immunosuppressive therapy (IST) have an especially grim prognosis. We report 14 patients (eight adults, six children) transplanted with double cord blood transplantation (dUCBT) for BMFS. Neutrophil recovery was observed in eight patients, with full donor chimerism of one unit, and acute GVHD in 10. With a median follow-up of 23 months, the estimated 2 years overall survival was 80 +/- 17% and 33 +/- 16% for patients with acquired and inherited BMFS, respectively. Transplantation of two partially HLA-matched UCB thus enables salvage treatment of high-risk patients with BMFS.
Assuntos
Doenças da Medula Óssea/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Adolescente , Adulto , Anemia Aplástica/terapia , Criança , Métodos Epidemiológicos , Anemia de Fanconi/terapia , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Terapia de Salvação/métodos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) have a potential immunomodulatory role in autoimmune disease; however, the qualitative properties and haematopoietic support capacity of MSCs derived from patients with autoimmune disease is unclear. OBJECTIVES: To further characterise phenotypically and functionally bone marrow (BM)-derived MSCs from patients with systemic sclerosis (SSc). METHODS: Key parameters of BM-derived MSC function and phenotype were assessed in 12 patients with SSc and compared with 13 healthy normal controls. The parameters included the ability to: form colony-forming unit fibroblasts (CFU-F), differentiate along the adipogenic and osteogenic lineages, express cell surface antigens defining the MSCs population, support normal haematopoiesis and suppress in vitro lymphocyte proliferation induced by either anti-CD3epsilon plus anti-CD28 monoclonal antibodies or the mixed lymphocyte reaction. RESULTS: SSc MSCs were shown to have a similar characteristic phenotype, capacities to form CFU-F and to differentiate along adipogenic and osteogenic lineages as those of healthy donor MSCs. The ability of SSc MSCs to support long-term haematopoiesis was also identical to that of controls. Both healthy donor and SSc BM MSCs reduced the proliferation of autologous and allogeneic peripheral blood mononuclear cells in a cell number dependent fashion. CONCLUSIONS: These results show that BM-derived MSCs from patients with SSc under the described culture conditions exhibit the same phenotypic, proliferative, differentiation potential and immunosuppressive properties as their healthy counterparts and could therefore be considered in an autologous setting. Further studies are needed to ensure the quality and safety of large-scale expansion of patient MSCs prior to their potential use in clinical trials.
Assuntos
Doenças Autoimunes/imunologia , Células da Medula Óssea/imunologia , Células-Tronco Mesenquimais/imunologia , Escleroderma Sistêmico/imunologia , Adulto , Doenças Autoimunes/terapia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Feminino , Fibroblastos/patologia , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunofenotipagem , Teste de Cultura Mista de Linfócitos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/terapiaRESUMO
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
Umbilical cord blood transplant (UCBT) is now used more frequently for transplanting children with high-risk malignancies. The advantages are the rapid availability of donor cells, the possibility of using HLA-mismatched transplants and the decreased risk of acute and chronic GvHD. The Eurocord registry has collected and analyzed data on unrelated CBTs performed in European Blood and Marrow Transplant Group (EBMT) and non-EBMT centers. The literature shows that after UCBT relapse rate (RR), disease-free survival and overall survival of children with acute leukemia are similar to other hematopoietic stem cell sources (matched unrelated BM). Disease status at the time of transplantation is found in several studies to be a very important determinant of long-term outcome. In conclusion, UCB is a valuable alternative source of hematopoietic stem cell transplantation in children with acute leukemia who need an allogeneic transplant, but lack a suitable sibling donor.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Intervalo Livre de Doença , Europa (Continente) , Humanos , Sistema de Registros , Transplante HomólogoRESUMO
Aplastic anemia is a rare disease in children that is most commonly idiopathic and less often a hereditary disorder. Hereditary bone marrow failure (BMF) syndromes, however, should be considered both in children and in adults before any attempt at treatment. Precise diagnosis is important because it will modify prognostic treatment options and the results of bone marrow transplantation. In this review, we will report recent results of treatment of Fanconi anemia and other hereditary BMF syndromes.
Assuntos
Anemia Hipoplástica Congênita/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas/métodos , Anemia Hipoplástica Congênita/genética , Pré-Escolar , Humanos , Estimativa de Kaplan-Meier , Agonistas Mieloablativos/uso terapêutico , Relações entre Irmãos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodosRESUMO
Bronchiolitis obliterans (BO) is a potentially life-threatening complication following allogeneic stem cell transplantation (SCT) and usually carries a poor prognosis. Immunosuppressive medications are the main treatment, but are rarely effective, especially when the disease is severe. Thus, both early detection and alternative therapeutic approaches of post SCT BO are needed. We report our experience with Budesonide/Formoterol, an inhaled steroid and long-acting bronchodilatator combination, in a group of patients with mild to moderately severe BO after SCT whose systemic immunosuppressive treatment had not been modified. Thirteen patients were treated. The diagnosis of BO was based on the presence of respiratory symptoms and air-trapping on expiratory lung high-resolution computed tomography in all patients, associated with irreversible airflow obstruction in seven cases. The median follow-up was 12.8 months (range: 5-29 months). All patients improved clinically, and both forced expiratory volume in 1 (FEV(1)) and mean expiratory flow values increased significantly during follow-up (534+/-268 ml in absolute values and 36+/-27% compared to pretreatment values for FEV(1); P<0.02). These encouraging results provide new insights in the therapeutic approach of BO after SCT and require confirmation in a larger group of patients with a longer follow-up.
Assuntos
Bronquiolite Obliterante/tratamento farmacológico , Broncodilatadores/administração & dosagem , Budesonida/administração & dosagem , Etanolaminas/administração & dosagem , Glucocorticoides/administração & dosagem , Transplante de Células-Tronco , Administração por Inalação , Adolescente , Adulto , Bronquiolite Obliterante/diagnóstico por imagem , Bronquiolite Obliterante/etiologia , Combinação de Medicamentos , Feminino , Seguimentos , Fumarato de Formoterol , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiografia , Transplante HomólogoRESUMO
We analyzed long-term outcomes and psycho-social aspects in 112 children with malignancies surviving 1 year after hematopoietic stem cell transplantation. At 10 years, overall survival was 75+/-5%, TRM 18+/-4% and relapse 14+/-3%; 10-year cumulative incidence of infections was 31+/-4%, cataract 44+/-4%, pulmonary dysfunction 20+/-4%, bone and joint complications 29+/-5%, hypothyroidism 36+/-4%, cardiac complications 11+/-3% and secondary malignancies 7+/-3%. Total body irradiation (TBI) was the most significant risk factor associated with cataract, pulmonary impairment, osteoarticular complications and hypothyroidism. Chronic graft-versus-host disease was associated with higher incidence of pulmonary dysfunction. The number of complications per patient increased with time. Half of the patients had psychological disturbance, 13 signs of depression and 16 a history of eating behavior disorders; 54% of patients with one or more long-term complications had psychological problems. Sixty-nine patients had learning difficulties and 36 achieved normal scholarship. With increased follow-up, development of late effects and of psycho-social disturbance are of major concern. While the use of single-dose TBI has now been abandoned, other risk factors are still of concern in the early 2000s.
Assuntos
Neoplasias Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas , Adolescente , Doenças Ósseas/etiologia , Doenças Ósseas/mortalidade , Doenças Ósseas/psicologia , Catarata/etiologia , Catarata/mortalidade , Catarata/psicologia , Criança , Pré-Escolar , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Transtornos da Alimentação e da Ingestão de Alimentos/mortalidade , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/psicologia , Humanos , Hipotireoidismo/etiologia , Hipotireoidismo/mortalidade , Hipotireoidismo/psicologia , Incidência , Lactente , Infecções , Artropatias/etiologia , Artropatias/mortalidade , Artropatias/psicologia , Pneumopatias/etiologia , Pneumopatias/mortalidade , Pneumopatias/psicologia , Masculino , Segunda Neoplasia Primária , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Irradiação Corporal TotalRESUMO
This paper describes the trends in haematopoietic stem cell transplantation (HSCT) activity for children in Europe over the last three decades. We analysed 31,713 consecutive paediatric HSCTs reported by the European Group for Blood and Marrow Transplantation (EBMT) centres between 1970 and 2002. Data were taken from the EBMT registry and were compared according to period and centre category (paediatric or combined). Since 1996, there has been a significant increase in the number of HSCTs performed exclusively by paediatric centres, as well as in the number of alternative donor HSCTs, and in the use of peripheral blood stem cells (P<0.0001). The number of allogeneic HSCTs (allo-HSCTs) for acute lymphoblastic leukaemia, acute myeloblastic leukaemia and chronic myeloid leukaemia remained stable, whereas it increased for myelodysplastic syndromes and lymphomas, and decreased significantly for non-malignant diseases (P<0.0001). Multivariate analysis showed that younger age, human leukocyte antigen genoidentical donors, HSCT performed after 1996 and transplant centres performing more than 10 allo-HSCT/year were all associated with decreased transplant-related mortality (TRM) (P<0.0001). The number of autologus HSCTs (auto-HSCTs) for acute leukaemia decreased significantly, whereas it increased for solid tumours (P<0.0001). Multivariate analysis showed that both auto-HSCT performed before 1996 and paediatric solid tumours (P<0.0001) had higher TRM. Indications for paediatric HSCT have changed considerably during the last seven years. These changes provide tools for decision making in health-care planning and counselling.
Assuntos
Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Transplante de Medula Óssea/estatística & dados numéricos , Criança , Coleta de Dados , Europa (Continente) , Humanos , Leucemia/terapia , Sistema de Registros , Transplante Autólogo , Transplante HomólogoRESUMO
Allogeneic hematopoietic cell transplantation (HCT) from siblings or unrelated donors (URD) during complete remission (CR) may improve leukemia-free survival (LFS) in FMS-like tyrosine kinase 3+ (FLT3+) acute myeloid leukemia (AML), which has poor prognosis because of high relapse rates. Umbilical cord blood (UCB) HCT outcomes are largely unknown in this population. We found that compared with sibling HCT, relapse risks were similar after UCB (n=126) (hazard ratio (HR) 0.86, P=0.54) and URD (n=91) (HR 0.81, P=0.43). UCB HCT was associated with statistically higher non-relapse mortality compared with sibling HCT (HR 2.32, P=0.02), but not vs URD (HR 1.72, P=0.07). All three cohorts had statistically nonsignificant 3-year LFS: 39% (95% confidence interval (CI): 30-47) after UCB, 43% (95% CI: 30-54) after sibling and 50% (95% CI: 40-60) after URD. Chronic graft-versus-host disease rates were significantly lower after UCB compared with either sibling (HR 0.59, P=0.03) or URD (HR 0.49, P=0.001). Adverse factors for LFS included high leukocyte count at diagnosis and HCT during CR2 (second CR). UCB is a suitable option for adults with FLT3+ AML in the absence of an human leukocyte antigen-matched sibling and its immediate availability may be particularly important for FLT3+ AML where early relapse is common, thus allowing HCT in CR1 (first CR) when outcomes are best.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/mortalidade , Recidiva Local de Neoplasia/mortalidade , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Doadores não Relacionados , Adulto JovemRESUMO
For patients with acquired severe aplastic anemia without a matched sibling donor and not responding to immunosuppressive treatment, bone marrow transplantation from a suitable alternative donor is often attempted. We examined risks of graft failure, graft-versus-host disease and overall survival after 318 alternative donor transplants between 1988 and 1998. Sixty-six patients received allografts from 1-antigen and 20 from >1-antigen mismatched related donors; 181 from matched and 51 from mismatched unrelated donors. Most patients were young, had had multiple red blood cell transfusions and poor performance score at transplantation. We did not observe differences in risks of graft failure and overall mortality by donor type. The probabilities of graft failure at 100 days after 1-antigen mismatched related donor, >1-antigen mismatched related donor, matched unrelated donor and mismatched unrelated donor transplants were 21, 25, 15 and 18%, respectively. Corresponding probabilities of overall survival at 5 years were 49, 30, 39 and 36%, respectively. Although alternative donor transplantation results in long-term survival, mortality rates are high. Poor performance score and older age adversely affect outcomes after transplantation. Therefore, early referral for transplantation should be encouraged for patients who fail immunosuppressive therapy and have a suitable alternative donor.
Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea , Adolescente , Adulto , Transplante de Medula Óssea/efeitos adversos , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/terapia , Antígenos HLA/análise , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do TratamentoRESUMO
We report long-term outcome in 102 patients with cCML transplanted from an HLA-identical sibling donor from 1982 to 1998. The conditioning regimen was based on cyclophosphamide associated with either total body irradiation (TBI) (37 patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin and methotrexate in the majority of the patients. Fifteen year overall survival was estimated at 53% (95% confidence interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis to transplantation, older age at time of transplantation and GvHD (acute grade III-IV or chronic extensive). The main cause of death was infection, related to GvHD in 69% of patients. Splenectomy also significantly increased the risk of bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late malignancies occurred in seven patients, four of whom had an invasive cancer. Other frequent late complications included cataracts, psychological depression, osteonecrosis and hypothyroidism. These complications were more frequent following splenectomy, TBI and in patients with chronic extensive GvHD. We conclude that allogeneic transplantation with a related donor can cure more than half of CML patients in chronic phase, although physicians should be alert to long-term complications.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Teste de Histocompatibilidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Seguimentos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Recidiva , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Doadores de Tecidos , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do TratamentoRESUMO
Thirty-seven patients with chronic granulocytic leukemia have been treated with supralethal chemoradiotherapy followed by transplantation of bone marrow from HLA-identical donors. All patients showed engraftment, and the Philadelphia chromosome (PH1) disappeared in each case. Four patients had syngeneic grafts before blast crisis and are still alive; 2 are in remission not maintained by therapy, and 2 others are receiving chemotherapy after having relapsed in the chronic phase. Thirty-three patients had allogeneic grafts; only 2 received the grafts during blast crisis, and neither is a long-term survivor. Of the 13 patients who had grafts in the accelerated phase, 6 died of complications related to the transplantation, and 1 died after a myeloblastic relapse. Thus 6 patients are in unmaintained remission with a median follow-up of 13 months. Eighteen patients received grafts in the chronic phase. All 10 survivors are in unmaintained remission with a median follow-up of 14 months; in this group, no patient has relapsed. The granulocytic hyperplasia of the chronic phase can be more effectively ablated than established blastic leukemia. The mortality rate of transplant-related complications must be weighted against the typical rate of progression of chronic granulocytic leukemia. Although a longer follow-up period is needed for full evaluation, bone marrow transplantation may now be offered to patients in the chronic phase in an attempt to achieve long-term survival or cure of more than one-half of these patients.
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide/terapia , Adolescente , Adulto , Contagem de Células Sanguíneas , Criança , Seguimentos , Doença Enxerto-Hospedeiro , Humanos , Leucemia Mieloide/mortalidade , Pessoa de Meia-Idade , Cromossomo Filadélfia , Esplenectomia , Transplante HomólogoRESUMO
Umbilical cord blood (UCB) emerged in the last 20 years as a valid alternative source of hematopoietic stem cell (HSC) in allogeneic transplantation setting, mainly in the absence of a fully human leucocyte antigen (HLA)-matched sibling. The probability of finding a matched unrelated donor through the registries varies from 20 to 70%, depending on the ethnicity of the patients. Therefore, patients in need may benefit of an HLA-mismatched hematopoietic stem cell transplantation from haploidentical donors or from UCB. One of the advantages of using UCB is the lower incidence of acute graft-versus-host-disease and allowance of greater HLA mismatch. Conversely, the low number of HSCs and lymphocytes and specific immunological features of T cells are associated with delayed engraftment and immune reconstitution and consequently, increased opportunistic infections. Nevertheless, retrospective studies showed similar results comparing UCB with other stem cell sources, both in pediatric and adult setting. The ability to use partially HLA-matched UCB units allows expanding the donor pool. Many UCB banks have strategies to increase their inventory including UCB grafts that have rare haplotypes. HLA and cell dose are very important factors associated with outcomes after umbilical cord blood transplantation (UCBT) that interact with each other. Increasing cell dose counterbalances the number of HLA disparities. Understanding those interactions, the role of HLA mismatches and other immunogenic factors, are important to allow clinicians to choose the best cord blood graft for patients. This review will describe the role of HLA in UCBT setting.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Antígenos HLA/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/imunologia , Doença Aguda , Adulto , Contagem de Células , Criança , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/genética , Haplótipos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Células-Tronco Hematopoéticas/citologia , Teste de Histocompatibilidade , Humanos , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/prevenção & controle , Resultado do Tratamento , Doadores não RelacionadosRESUMO
Thirty-two children ranging in age from 1.5 to 16 years with poor-prognosis acute lymphoblastic leukemia (ALL) were treated with myeloablative immunosuppressive therapy consisting of cyclophosphamide (CPM) and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) while in first complete remission (CR). The main reasons for assignment to BMT were WBC count greater than 100,000/microL, structural chromosomal abnormalities, and resistance to initial induction therapy. All children were transplanted with marrow from histocompatible siblings. Twenty-seven patients are alive in first CR for 7 to 82 months post-transplantation (median, 30 months). The actuarial disease-free survival rate is 84.4% (confidence interval, 7.2% to 29%) and the actuarial relapse rate is 3.5% (confidence interval, 0.9% to 13%). Four patients died of transplant-related complications, 16 developed low-grade acute graft-v-host disease (GVHD), and six developed chronic GVHD. The very low incidence of relapse (one of 28 long-term survivors) precluded the determination of the prognostic significance of the different poor-outcome features. Moreover, two infants treated with busulfan, CPM, and cytarabine (Ara-C) relapsed promptly in the marrow. In summary, as a means of providing long-term disease-free survival and possible cure, BMT should be considered for children with ALL presenting poor-prognostic features, particularly certain chromosomal translocations [t(4;11), t(9;22)], very high WBC counts, notably if associated with a non-T immunophenotype, and, perhaps, a poor response to initial therapy with corticosteroids (CS), or infants less than 6 months of age.
Assuntos
Transplante de Medula Óssea , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Multicêntricos como Assunto , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: Optimal postremission therapy remains controversial in adult patients with acute lymphoblastic leukemia (ALL). In a large multicentric trial (LALA87), we compared allogeneic bone marrow transplantation (BMT) with other postremission therapies (chemotherapy or autologous transplantation) using the result of the human leukocyte antigen (HLA) typing as a random allocation. PATIENTS AND METHODS: Patient eligibility requirements were as follows: (1) inclusion in LALA87 trial, (2) complete response to induction or salvage therapy, (3) age 15 to 40 years, and (4) at least one potential sibling donor. Patients with an HLA-identical sibling were assigned to the BMT group, while patients without a sibling donor constituted the control group. Allogeneic transplantation was scheduled for patients in the BMT group; in the control group, patients were randomly allocated to receive chemotherapy or autologous transplantation. RESULTS: Of 284 eligible points, 257 entered the study: 116 were allocated to the BMT group and 141 to the control group. The 5-year survival rates were not statistically significantly different between the two groups. When only patients with high-risk ALL were considered (those with [1] Philadelphia chromosome [Ph1] ALL, [2] null or undifferentiated ALL, or [3] c-ALL with either age greater than 35 years or WBC count > 30 x 10(9)/L or time to achieve complete remission > 4 weeks), overall survival (P = .03) and disease-free-survival (P = .01) were better for the BMT group compared with the control group (5-year overall survival rates, 44% v 20%; 5-year disease-free survival rates, 39% v 14%). CONCLUSION: Allogeneic transplantation does not improve survival in patients with standard-risk ALL and should be recommended only for patients with adverse prognostic factors.