Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Pediatr Hematol Oncol ; 42(1): e38-e41, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31688620

RESUMO

BACKGROUND: Hydroxyurea is a well-established disease-modifying medication for sickle cell disease (SCD). At some institutions, hydroxyurea can only be ordered by "chemotherapy-certified" providers which may not include pediatric resident physicians. METHODS: We conducted a survey of 39 American pediatric hospitals regarding their policy on resident hydroxyurea ordering for SCD. Our institution changed its policy in June 2016 to allow residents to order hydroxyurea for hospitalized patients with SCD who were already on hydroxyurea at home. We conducted a retrospective review of the medical records of a random sample of patients with SCD on hydroxyurea admitted the year before and the year after this policy change. RESULTS: In our national survey, 51% of surveyed hospitals allowed residents to order hydroxyurea, 19% required a second signature, and 30% did not allow residents to order hydroxyurea. In our institutional study, patients after the policy change were significantly more likely to have received their home hydroxyurea by hospital day 1: before 62/90 (69%) versus after 105/119 (88%), P=0.0005. The proportion of patients who inappropriately received hydroxyurea was very low in both groups: before 1/91 (1%) versus after 3/126 (2%), P=0.64, with no serious adverse clinical events due to inappropriate hydroxyurea administration. CONCLUSIONS: Considerable national variation in practice currently exists in regards to resident hydroxyurea ordering hospital policies. A policy allowing residents to order hydroxyurea significantly increased the likelihood of a patient receiving hydroxyurea while hospitalized with no significant increase in inappropriate hydroxyurea administration. Resident hydroxyurea ordering seems safe and beneficial.

2.
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.

3.
Pediatr Blood Cancer ; 66(5): e27601, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30609269

RESUMO

BACKGROUND: Sickle cell disease (SCD) is increasingly recognized as a red blood cell disorder modulated by abnormally increased inflammation. We have previously shown that in patients with SCD not on a disease-modifying therapy (hydroxyurea or chronic transfusions), natural killer (NK) cell numbers are increased. In the current study, we further investigated the NK cell function to determine if there was evidence of increased activation and cytotoxicity. PROCEDURE: We conducted a cross-sectional study of 44 patients with HbSS/HbSß0 thalassemia at steady state (hydroxyurea = 13, chronic transfusion = 11, no disease-modifying therapy = 20) and 23 healthy controls. Using a fresh blood sample, NK immunophenotyping was performed as follows: NK cells (CD3- CD56+ lymphocytes) were evaluated for makers associated with activation (NKG2D, NKp30, NKp44, and CD69) and maturity (CD57, killer immunoglobulin-like receptors (KIR), and CD56dim). Degranulation and cytotoxicity assays were performed to evaluate NK cell function. RESULTS: Patients with SCD who were not on disease-modifying therapy had a higher number of NK cells with an immunophenotype associated with increased cytotoxicity (NKG2D+ , NKp30+ , CD56dim+ , and KIR+ NK cells) compared with healthy controls and patients on hydroxyurea. NK cells from SCD patients not on disease-modifying therapy demonstrated significantly increased cytotoxicity (measured by assaying NK cell killing of the K562 cell line) compared with healthy controls (P = 0.005). Notably, NK cell cytotoxicity against K562 cells in the hydroxyurea or chronic transfusion patients was not significantly different from that in healthy controls. CONCLUSION: SCD is associated with increased NK cell function as well as increased NK cell numbers, which appears to be normalized with disease-modifying therapy.


Assuntos
Anemia Falciforme/imunologia , Anemia Falciforme/patologia , Biomarcadores/metabolismo , Citotoxicidade Imunológica/imunologia , Células Matadoras Naturais/imunologia , Adolescente , Adulto , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/metabolismo , Antidrepanocíticos/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Hidroxiureia/uso terapêutico , Imunofenotipagem , Lactente , Células Matadoras Naturais/metabolismo , Masculino , Prognóstico , Adulto Jovem
4.
Pediatr Blood Cancer ; 65(8): e27102, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29667775

RESUMO

Pre-implantation genetic diagnosis (PGD) is an option for parents who have a child with sickle cell disease (SCD) to have another child without SCD. We conducted a survey of 19 parents with at least one child with SCD to investigate views on PGD. Before education, 44% of parents were aware of PGD. All parents rated PGD education as important. All parents considering another child also reported interest in using PGD if insurance covered its costs. Parents who have a child with SCD appear to be interested in PGD and educational tools informing this group about PGD should be developed.


Assuntos
Anemia Falciforme , Conhecimentos, Atitudes e Prática em Saúde , Pais/educação , Pais/psicologia , Diagnóstico Pré-Implantação/psicologia , Análise Citogenética/métodos , Feminino , Humanos , Gravidez
5.
Am J Hematol ; 90(12): 1135-41, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26361243

RESUMO

Alloimmunization against red blood cell (RBC) antigens is a cause of morbidity and mortality in transfused patients with sickle cell disease (SCD). To investigate distinguishing characteristics of patients who develop RBC alloantibodies after transfusion (responders) versus those who do not (non-responders), a cross-sectional study of 90 children with SCD on chronic RBC transfusion therapy at a single institution was conducted in which 18 immune parameters (including T and B cell subsets) were tested via flow cytometry, and medical records were reviewed. RBC alloimmunization was present in 26/90 (29%) patients, with anti-E, K, and C among the most commonly detected alloantibodies despite prophylactic matching for these antigens at the study institution. In addition, RBC autoantibodies had been detected in 18/26 (69%) of alloimmunized versus 7/64 (11%) of non-alloimmunized patients (P < 0.0001). Alloimmunized patients were significantly older (median 13.0 years vs. 10.7 years, P = 0.010) and had more RBC unit exposures (median 148 U vs. 82 U, P = 0.020) than non-alloimmunized patients. Sex, age at initiation of chronic transfusion, splenectomy, stroke, and transfusion outside of the study institution were not significantly associated with RBC alloimmunization. Alloimmunized patients had a significantly increased percentage of CD4+ T memory cells compared to non-alloimmunized patients (57% vs. 49%, P = 0.0047), with no other significant differences in immune cell subsets or laboratory values detected between these groups. Additional research of RBC alloimmunization is needed to optimize transfusion therapy and to develop strategies to prevent alloimmunization.


Assuntos
Anemia Falciforme/sangue , Transfusão de Eritrócitos/métodos , Imunofenotipagem/métodos , Isoanticorpos/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Adulto Jovem
6.
Br J Haematol ; 170(2): 247-56, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25891976

RESUMO

Blood transfusions can induce alloantibodies to antigens on red blood cells (RBCs), white blood cells and platelets, with these alloantibodies affecting transfusion and transplantation. While transfusion-related alloimmunization against RBC antigens and human leucocyte antigens (HLA) have been studied, transfusion-related alloimmunization to minor histocompatibility antigens (mHA), such as H-Y antigens, has not been clinically characterized. We conducted a cross-sectional study of 114 children with sickle cell disease (SCD) and tested for antibodies to 5 H-Y antigens and to HLA class I and class II. Few patients had H-Y antibodies, with no significant differences in the prevalence of any H-Y antibody observed among transfused females (7%), transfused males (6%) and never transfused females (4%). In contrast, HLA class I, but not HLA class II, antibodies were more prevalent among transfused than never transfused patients (class I: 33% vs. 13%, P = 0·046; class II: 7% vs. 8%, P = 0·67). Among transfused patients, RBC alloantibody history but not amount of transfusion exposure was associated with a high (>25%) HLA class I panel reactive antibody (Odds ratio 6·8, 95% confidence interval 2·1-22·3). These results are consistent with immunological responder and non-responder phenotypes, wherein a subset of patients with SCD may be at higher risk for transfusion-related alloimmunization.


Assuntos
Anemia Falciforme/imunologia , Anemia Falciforme/terapia , Transfusão de Eritrócitos , Antígeno H-Y/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Isoanticorpos/imunologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Transfusão de Eritrócitos/efeitos adversos , Feminino , Humanos , Imunofenotipagem , Isoanticorpos/sangue , Masculino , Razão de Chances , Adulto Jovem
7.
Br J Haematol ; 169(4): 574-83, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25753210

RESUMO

Sickle cell disease (SCD) is increasingly appreciated as an inflammatory condition associated with alterations in immune phenotype and function. In this cross-sectional study we performed a multiparameter analysis of 18 immune markers in 114 paediatric SCD patients divided by treatment group [those receiving hydroxycrabamide (HC, previously termed hydroxyurea), chronic transfusion (CT), or no disease-modifying therapy] and 29 age-matched African American healthy controls. We found global elevation of most immune cell counts in SCD patients receiving no disease-modifying therapy at steady state. Despite the decrease in percentage of haemoglobin S associated with CT therapy, the abnormal cellular immune phenotype persisted in patients on CT. In contrast, in both univariate and multivariate analysis, treatment with HC was associated with normalization of the vast majority of leucocyte populations. This study provides additional support for HC treatment in SCD, as it appears that HC decreases the abnormally elevated immune cell counts in patients with SCD.


Assuntos
Anemia Falciforme/imunologia , Anemia Falciforme/terapia , Antidrepanocíticos/administração & dosagem , Transfusão de Sangue , Hidroxiureia/administração & dosagem , Leucócitos/imunologia , Adolescente , Afro-Americanos , Anemia Falciforme/sangue , Criança , Seguimentos , Humanos , Contagem de Leucócitos
8.
Blood ; 124(6): 861-6, 2014 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-24963044

RESUMO

Hematopoietic stem cell transplant (HSCT) is the only cure for sickle cell disease (SCD). HSCT using an HLA-identical sibling donor is currently an acceptable treatment option for children with severe SCD, with expected HSCT survival >95% and event-free survival >85%. HSCT for children with less severe SCD (children who have not yet suffered overt disease complications or only had mild problems) is controversial. It is important to consider the ethical issues of a proposed study comparing HLA-identical sibling HSCT to best supportive care for children with less severe SCD. In evaluating the principles of nonmaleficence, respect for individual autonomy, and justice, we conclude that a study of HLA-identical sibling HSCT for all children with SCD, particularly hemoglobin SS and Sß(0)-thalassemia disease, is ethically sound. Future work should explore the implementation of a large trial to help determine whether HSCT is a beneficial treatment of children with less severe SCD.


Assuntos
Anemia Falciforme/terapia , Transplante de Células-Tronco Hematopoéticas/ética , Anemia Falciforme/complicações , Anemia Falciforme/mortalidade , Criança , Ensaios Clínicos como Assunto/ética , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Doadores Vivos/ética , Fatores de Risco , Irmãos
9.
Pediatr Blood Cancer ; 61(5): 810-4, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24357218

RESUMO

BACKGROUND: Daunorubicin, a component of the four-drug induction chemotherapy regimen for de novo pediatric high-risk acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy), was unavailable in 2011 due to a national drug shortage. During this time, our institution substituted mitoxantrone 6.25 mg/m(2) for daunorubicin 25 mg/m(2) on induction Days 1, 8, 15, and 22. While mitoxantrone has been shown to be effective for relapsed ALL, it has not been studied in de novo pediatric ALL/LLy. PROCEDURE: We conducted a retrospective cohort study of newly diagnosed patients with ALL or LLy at our institution 1/2009-4/2013 to compare induction toxicity and response of patients treated with mitoxantrone versus daunorubicin. RESULTS: Eleven patients received mitoxantrone, 121 patients received daunorubicin. Induction toxicities including deaths, intensive care unit admissions, fever, bacteremia, and invasive fungal disease were similar for the two groups. Mean number of days hospitalized during induction was also similar (mitoxantrone 9.7 days vs. daunorubicin 11.2 days, P = 0.60). Minimal residual disease prevalence at the end of induction was not significantly different (mitoxantrone 33.3% vs. daunorubicin 23.0%, P = 0.44). The only significant difference between the groups was that a higher proportion of patients who received mitoxantrone had consolidation delayed due to myelosuppression (mitoxantrone 30.0% vs. daunorubicin 6.0%, P = 0.03). CONCLUSION: Induction toxicity and response for new ALL/LLy patients treated with mitoxantrone in place of daunorubicin were similar to the toxicity and response seen with conventional daunorubicin. Mitoxantrone is a reasonable replacement for daunorubicin in times of drug shortage.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Asparaginase/administração & dosagem , Criança , Daunorrubicina/administração & dosagem , Dexametasona/administração & dosagem , Substituição de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Mitoxantrona/administração & dosagem , Polietilenoglicóis/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Prednisona/administração & dosagem , Prognóstico , Indução de Remissão , Vincristina/administração & dosagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA