Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Br J Haematol ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674662

RESUMO

The relevance of donor-specific human leukocyte antigen (HLA) antibodies in HLA-mismatched haematopoietic cell transplant (HCT) is known, but the importance of HLA antibodies in HLA-matched HCT is unclear. We hypothesized that HLA antibodies detected before HCT would cause platelet transfusion refractoriness during HCT and investigated this in a multi-centre study. Pre-HCT samples from 45 paediatric patients with sickle cell disease (SCD) undergoing HLA-matched HCT were tested for HLA class I antibodies. The number of platelet transfusions received before day +45 was compared between those with and without antibodies. Thirteen of 45 (29%) patients had a positive HLA class I antibody screen, and these patients received significantly more platelet transfusions than patients without antibodies (median 19 vs. 7·5, P = 0·028). This platelet transfusion association remained significant when controlling for conditioning regimen. Among alloimmunized patients, there was no association between the panel-reactive antibody and the number of platelet transfusions. Patients with HLA class I antibodies also had a higher incidence of acute graft-versus-host disease (GVHD): 6/13 (46%) vs. 3/32 (9%), P = 0·011. Pre-HCT HLA class I alloimmunization is associated with increased platelet transfusion support and acute GVHD in paediatric HLA-matched HCT for SCD. Further studies are needed to investigate the pathobiology of this association.

2.
Pediatr Transplant ; 23(6): e13496, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31124253

RESUMO

INTRODUCTION: The effects of RIC for HSCT on male fertility remain unknown. We investigated spermatogenesis and gonadal hormonal status among adolescent male patients who received RIC HSCT for non-malignant diseases. PATIENTS AND METHODS: Patients with non-malignant disease who had undergone a RIC HSCT were recruited and evaluated for spermatogenesis via semen analysis and gonadal hormonal function via serum hormone levels. Those who had received prior chemotherapy or radiation were excluded from the study. We reviewed the charts to record demographic factors, conditioning regimen and complications during and after transplant. RESULTS: Five patients were enrolled. The median age at the time of transplant was 15 years (range, 11-19 years), and the median time between bone marrow transplant and semen analysis was 5 years (range, 3-11 years). Median age of patients was 20 years (range, 18-25 years) at the time of the study. Serum FSH and LH levels were elevated in four patients, and inhibin B levels were low for age in three patients. Semen analysis showed two patients had azoospermia, and the remaining three patients showed severe oligozoospermia. Normal morphology and motility were seen in only one patient. CONCLUSION: This case series suggests that RIC transplants may be associated with impaired spermatogenesis and sequential follow-up is necessary given the potential for either permanent impairment or delayed recovery. Further larger studies are needed to confirm these findings.

3.
Transfusion ; 58(9): 2122-2127, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30179262

RESUMO

BACKGROUND: After hematopoietic stem cell transplantation (HSCT) autoimmune hemolytic anemia (AIHA) is a known and fairly common complication. It is often refractory to conventional therapies including corticosteroids, intravenous immunoglobulin, splenectomy, and the more recently described use of monoclonal antibodies. The high morbidity associated with these severe persistent cases elucidates the gaps in alternative therapies available for treatment. STUDY DESIGN AND METHODS: We described the successful use of abatacept for severe refractory AIHA after HSCT in three patients. RESULTS: Three pediatric patients with refractory AIHA after allogeneic stem cell transplantation were observed to be unresponsive to multitude immunosuppressive therapies, resulting in persistent transfusion dependency. Treatment with abatacept, a fusion protein that inhibits T-cell activation by binding to CD80/CD86 on antigen-presenting cells (APCs), thus blocking the required CD28 interaction between APCs and T cells, resulted in the resolution of hemolysis. CONCLUSION: Abatacept may provide significant clinical benefit in the management of AIHA after HSCT.


Assuntos
Abatacepte/uso terapêutico , Anemia Hemolítica Autoimune/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Adolescente , Anemia Hemolítica Autoimune/etiologia , Anemia Falciforme/terapia , Bacteriemia/complicações , Tipagem e Reações Cruzadas Sanguíneas , Criança , Pré-Escolar , Resistência a Medicamentos , Substituição de Medicamentos , Feminino , Fatores de Troca do Nucleotídeo Guanina/deficiência , Humanos , Síndrome de Job/complicações , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Staphylococcus aureus Resistente à Meticilina , Pneumonia por Pneumocystis/complicações , Indução de Remissão , Estudos Retrospectivos , Infecções Estafilocócicas/complicações , Viroses/complicações
4.
Biol Blood Marrow Transplant ; 24(3): 537-541, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29196075

RESUMO

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by a triad of immunodeficiency, eczema, and thrombocytopenia. Currently, hematopoietic stem cell transplantation (HSCT) is the most reliable curative treatment with excellent results for patients with HLA-matched family or unrelated donors. However, even after fully myeloablative preparative regimens, mixed donor chimerism is a potential concern. We performed a retrospective chart review of 12 children who underwent allogeneic HSCT for WAS to report our experience. The median age at transplant was 10.5 months (range, 3 to 39). The median nucleated cell dose from the marrow was 4.55 × 109/kg (range, .3 to 7.9). The median times to neutrophil and platelet engraftment were 19 days (range, 13 to 27) and 18.5 days (range, 12 to 31), respectively. The rate of overall survival was 92% with median follow-up of 67 months (range, 3 to 146). Two patients developed grade IV acute graft-versus-host disease, and 1 died on day +99. Five of 12 patient's (42%) had mixed donor chimerism (range, 12% to 85%) at day +180. None of the pretransplant patient parameters was predictive of mixed chimerism. Nonetheless, of these 5 patients, 2 had normalization of the platelet count despite the mixed chimerism, 2 had full donor chimerism after receiving a second transplant with the same donor, and 1 remains transfusion dependent awaiting a second transplant. Hence, even with a significant rate of mixed chimerism, HSCT provides substantial benefit to WAS patients, with excellent overall survival.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Síndrome de Wiskott-Aldrich , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Síndrome de Wiskott-Aldrich/sangue , Síndrome de Wiskott-Aldrich/mortalidade , Síndrome de Wiskott-Aldrich/terapia
5.
Pediatr Blood Cancer ; 65(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28960811

RESUMO

BACKGROUND: Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) are frequently diagnosed with vitamin D deficiency, which may impact outcomes. OBJECTIVES: To estimate the prevalence of vitamin D deficiency and examine its association with short-term survival in pediatric HSCT patients. METHODS: Patients undergoing HSCT at Phoenix Children's Hospital were retrospectively identified. Routine serum 25-hydroxyvitamin D measurements were described prior to transplant and at 100 days and 1-year post-HSCT. Associations of pre-HSCT vitamin D groups (i.e., normal ≥30 ng/ml, insufficient 20-29 ng/ml, and deficient <30 ng/ml) with demographics, clinical factors, and outcomes were examined using nonparametric tests and Cox proportional hazards analyses. RESULTS: Among 72 study subjects, the median vitamin D pre-HSCT was 26 ng/ml (range: 19-34 ng/ml). Levels were insufficient and deficient in 25 (35%) and 20 (28%) patients, respectively, with only two (3%) patients on supplemental therapy pre-HSCT. Despite supplemental therapy provided to 46 (74%) subjects, insufficient/deficient rates did not significantly change between pre-HSCT and 100 days post-HSCT, but mean vitamin D levels significantly increased by 1-year post-HSCT (P = 0.01).Vitamin D pre-HSCT was not associated with the development of acute or chronic graft-versus-host disease (GVHD) or delayed engraftment. Overall 1-year survival was significantly lower for patients with deficient (65%) compared to normal (93%) pre-HSCT vitamin D (P = 0.001). CONCLUSION: Suboptimal vitamin D levels are common in pediatric patients scheduled to receive HSCT and are associated with lower overall 1-year survival. Further study is warranted to delineate the mechanisms underlying the role of vitamin D in successful HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Vitamina D/análogos & derivados , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasias/sangue , Neoplasias/mortalidade , Neoplasias/terapia , Taxa de Sobrevida , Fatores de Tempo , Vitamina D/sangue , Deficiência de Vitamina D/terapia
6.
Biol Blood Marrow Transplant ; 21(7): 1321-5, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25840334

RESUMO

Genetically derived hematologic cytopenias are a rare heterogeneous group of disorders. Allogeneic hematopoietic cell transplantation (HCT) is curative but offset by organ toxicities from the preparative regimen, graft rejection, graft-versus-host disease (GVHD), or mortality. Because of these possibilities, consideration of HCT can be delayed, especially in the unrelated donor setting. We report a prospective multicenter trial of reduced-intensity conditioning (RIC) with alemtuzumab, fludarabine, and melphalan and HCT in 11 children with marrow failure of genetic origin (excluding Fanconi anemia) using the best available donor source (82% from unrelated donors). The median age at transplantation was 23 months (range, 2 months to 14 years). The median times to neutrophil (>500 × 10(6)/L) and platelet (>50 × 10(9)/L) engraftment were 13 (range, 12 to 24) and 30 (range, 7 to 55) days, respectively. The day +100 probability of grade II to IV acute GVHD and the 1-year probability of limited and extensive GVHD were 9% and 27%, respectively. The probability of 5-year overall and event-free survival was 82%; 9 patients were alive with normal blood counts at last follow-up and all were successfully off systemic immunosuppression. In patients with genetically derived severe hematologic cytopenias, allogeneic HCT with this RIC regimen was successful in achieving a cure. This experience supports consideration of HCT early in such patients even in the absence of suitable related donors.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Agonistas Mieloablativos/uso terapêutico , Neutropenia/terapia , Trombocitopenia/terapia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adolescente , Alemtuzumab , Anticorpos Monoclonais Humanizados/uso terapêutico , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/uso terapêutico , Lactente , Masculino , Melfalan/uso terapêutico , Neutropenia/genética , Neutropenia/imunologia , Neutropenia/mortalidade , Estudos Prospectivos , Risco , Irmãos , Análise de Sobrevida , Trombocitopenia/genética , Trombocitopenia/imunologia , Trombocitopenia/mortalidade , Transplante Homólogo , Resultado do Tratamento , Doadores não Relacionados , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
7.
Pediatr Blood Cancer ; 62(7): 1270-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25755151

RESUMO

BACKGROUND: Hematopoietic cell transplantation (HCT) is curative in patients with severe aplastic anemia (SAA). HCT is considered at presentation when a HLA-matched related donor (MRD) is available and has a high success rate. Unrelated donor (URD) transplants are typically undertaken if immunosuppressive therapy fails. Increased toxicity and graft rejection are often encountered in this setting. PROCEDURE: We report a prospective multi-center trial of HCT in 17 children with SAA following novel reduced intensity conditioning with alemtuzumab, fludarabine and melphalan, and the best available donor. Nine were URD transplants matched at 7-8/8 loci, and performed following failure of immune suppression. Median follow up was 61 months (range 6-128). RESULTS: All patients engrafted. Estimated 5 year event-free and overall-survival was 88% (95%CI 65.7-96.7). Five year overall survival for MRD and URD transplants was 100% and 78% (95%CI 45-93.6) respectively. Median times to neutrophil and platelet engraftment was 14 (range 10-27) and 23.5 (range 11-65) days respectively. Treatment related mortality was 12%. The incidence of grade II-IV and III-IV acute graft-versus-host disease was 29% and 18% respectively. At two years, all but one patient discontinued immunosuppression successfully. Laboratory measures of immune reconstitution normalized at one year and infection rates were low in the latter part of the first year. CONCLUSIONS: HCT using this RIC approach was well tolerated and successful in achieving donor engraftment and early immune reconstitution with good quality of life free of immune suppression. Children with SAA can be successfully transplanted using alemtuzumab based conditioning.


Assuntos
Anemia Aplástica/terapia , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Adolescente , Alemtuzumab , Anemia Aplástica/complicações , Anemia Aplástica/mortalidade , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Taxa de Sobrevida , Transplante Homólogo , Doadores não Relacionados
8.
J Pediatr Hematol Oncol ; 37(2): e94-e101, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25333837

RESUMO

Single fraction total body irradiation (SFTBI) as part of a myeloablative preparative regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies was shown to have similar survival compared with fractionated total body irradiation (FTBI)-containing regimens, with less acute toxicity. The objective of this study was to determine long-term toxicity >2 years following SFTBI-based HSCT. Twenty-one patients were evaluated at a median follow-up of 6.8 years. Thyroid dysfunction was found in 21% of patients, 1 of whom (5.2%) was symptomatic; 23% had gonadal failure; 50% of patients with growth potential had linear growth disturbance; 27% had mild to moderate pulmonary disease; and 25% had cataracts. Intelligence quotient was stable. cGVHD was present in 28%, and 4 patients (19%) were on immune suppression 2 years posttransplant. Overall survival subsequent to 2 years posttransplant was 76% in this cohort of patients. No secondary malignancies were observed. In conclusion, the toxicities of SFTBI occurred at similar or reduced frequency compared with FTBI. SFTBI should be considered for patients who may benefit from a radiation-containing HSCT preparative regimen.


Assuntos
Ciclofosfamida/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Irradiação Corporal Total/efeitos adversos , Adolescente , Adulto , Antineoplásicos Alquilantes/efeitos adversos , Criança , Pré-Escolar , Terapia Combinada , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Humanos , Lactente , Masculino , Prognóstico , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
9.
J Clin Rheumatol ; 20(4): 224-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24847751

RESUMO

Scurvy is rare in developed countries but is known to cause lower-extremity pain and refusal to ambulate in children. Since the discovery of the link between scurvy and dietary deficiency of ascorbic acid, there has been a substantial decrease in its prevalence and recognition. Here we describe 3 cases of scurvy in young children presenting with difficulty walking. Only 1 of 3 patients had gingival lesions at the initial presentation. Two cases underwent an extensive evaluation for hematologic and rheumatologic diseases before the diagnosis of scurvy was made. Dietary histories eventually revealed that all 3 patients had sharply limited intake of fruits and vegetables secondary to oral aversion, and 1 patient had autism. Radiographic changes of long bones were observed in all patients. Interestingly, all patients had concomitant vitamin D deficiency. After replacement with vitamin C, all patients recovered and started to walk again with improved leg pain. These clinical manifestations and radiologic findings highlight the importance for rheumatologists to have a higher index of suspicion for scurvy in nonambulatory children.


Assuntos
Limitação da Mobilidade , Escorbuto/diagnóstico , Ácido Ascórbico/uso terapêutico , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Escorbuto/tratamento farmacológico , Caminhada
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA