Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 88
Filtrar
2.
Artigo em Inglês | MEDLINE | ID: mdl-31927102

RESUMO

Serious viral infections, due to delayed immune reconstitution, are a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Thus, many transplant centers prospectively track cellular immune recovery by evaluating absolute cell numbers and the phenotypic profile of reconstituting T cell subsets to identify individuals who are at highest risk of infection. Conventional assessments, however, fail to measure either the antigen specificity or functional capacity of reconstituting cells-both factors that correlate with endogenous antiviral protection. In this pilot study, we sought to address this limitation by prospectively investigating the tempo of endogenous immune reconstitution in a cohort of 23 pediatric HSCT patients using both quantitative (flow cytometry) and qualitative (IFNγ ELISpot) measures, which we correlated with either the presence or absence of infections associated with cytomegalovirus, adenovirus, Epstein-Barr virus, BK virus, human herpes virus 6, respiratory syncytial virus, parainfluenza, influenza, and human metapneumovirus. We present data spanning 12 months post-transplant demonstrating the influence of conditioning on immune recovery and highlighting the differential impact of active viral replication on the quantity and quality of reconstituting cells. Judicious use of standard (phenotypic) and novel (functional) monitoring strategies can help guide the clinical care and personalized management of allogenic HSCT recipients with infections.

3.
Pediatr Blood Cancer ; 67(3): e28070, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31774252

RESUMO

BACKGROUND: Transplant-associated thrombotic microangiopathy (TA-TMA) occurs after hematopoietic stem cell transplantation (HSCT) and is characterized by microvascular thrombosis and end-organ injury particularly of the kidneys. TA-TMA is challenging to diagnose and treat, which can lead to long-term complications and death in patients with severe disease. Studies have shown that genetic abnormalities of the alternative complement pathway (AP) are associated with TA-TMA. We hypothesized that patients with TA-TMA may generate elevated levels of the AP activation product, Ba, compared with HSCT patients without TA-TMA. PROCEDURE: We longitudinally measured plasma levels of complement activation products C3a, Ba, and C5a in 14 HSCT patients: 7 with TA-TMA and 7 without TA-TMA. We assessed renal function by calculating estimated glomerular filtration rate (eGFR) and correlated the extent of AP activation with renal dysfunction in both patient populations. RESULTS: The median days from HSCT to study enrollment were 154 (39-237) in the TA-TMA group and 84 (39-253) in the HSCT group without TA-TMA. Median Ba levels (ng/mL) at enrollment were 1096.9 (826.5-1562.0) in the TA-TMA group and 725.7 (494.7-818.9) in the HSCT group without TA-TMA (P = 0.007). Over the study duration, Ba levels inversely correlated with eGFR. There were no differences in C3a, C5a, or sC5b9 levels between the two populations at any measured interval. CONCLUSIONS: We conclude in this preliminary study that Ba protein may serve as a marker for TA-TMA, and furthermore, that components generated in the early phase of AP activation may be involved in the pathogenesis of renal endothelial injury in TA-TMA.

4.
Blood Adv ; 3(18): 2689-2695, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31511228

RESUMO

Allogeneic hematopoietic stem cell transplant (HSCT) for relapsed pediatric non-Hodgkin lymphoma (NHL) is often reserved for patients with certain NHL subtypes or high-risk disease whereas the remainder receive autologous HSCT. Given the aggressive nature of pediatric NHL, we performed allogeneic HSCTs for all patients regardless of disease risk. We report overall survival (OS) and prognostic variables in 36 pediatric patients who underwent allogeneic HSCT between 1998 and 2016. OS at 3 years was 67%. The 3-year OS varied based on NHL subtype: 100% for anaplastic large cell lymphoma (n = 14), 63% for diffuse large B-cell lymphoma (n = 8), 17% for lymphoblastic lymphoma (LL; n = 9) and 80% for other subtypes combined (n = 5). Disease status influenced outcome with 3-year OS of 100% for patients in complete remission (n = 15), 59% with partial remission (PR; n = 17), and 0% with progressive/stable disease (n = 3) (P = .004). Of the 17 patients in PR, all 6 with LL died of relapsed disease, whereas the other 11 attained remission after HSCT and remained disease-free. The cumulative incidence of relapse after HSCT for LL was 78% compared with 15% for all other NHL subtypes combined (P < .0001). Cumulative incidence of nonrelapse mortality (NRM) was low in our cohort at 6%. Hence, allogeneic HSCT is a well-tolerated and useful therapeutic option with low rates of NRM and relapse for all NHL subtypes except LL with active disease at HSCT.

5.
Blood Adv ; 3(17): 2571-2580, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31481503

RESUMO

Cytomegalovirus (CMV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), and standard antiviral therapies are associated with significant side effects and development of drug-resistant mutants. Adoptively transferred donor-derived CMV-specific T cells (CMVSTs) can provide an alternative treatment modality with few side effects but are not widely available due to their patient-specific nature. Here we report the establishment and use of a bank of CMVSTs derived from just 8 CMV-seropositive donors, with HLA types representing the diverse US population, as an "off-the-shelf" therapy to treat drug-refractory infections. To date, we have screened 29 patients for study participation and identified a suitable line, with ≥2 of 8 shared HLA antigens, for 28 (96.6%) patients with a median of 4 shared HLA antigens. Of these, 10 patients with persistent/refractory CMV infections or disease were eligible for treatment; a single infusion of cells produced 3 partial responses and 7 complete responses, for a cumulative response rate of 100% (95% confidence interval, 69.2-100) with no graft-versus-host disease, graft failure, or cytokine release syndrome. Potential wider use of the tested CMVSTs across transplant centers is made more feasible by our ability to produce sufficient material to generate cells for >2000 infusions from a single donor collection. Our data indicate that a "mini" bank of CMVSTs prepared from just 8 well-chosen third-party donors can supply the majority of patients with an appropriately matched line that produces safe and effective anti-CMV activity post-HSCT.

7.
Blood Adv ; 3(14): 2057-2068, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31292125

RESUMO

Adoptive transfer of virus-specific T cells (VSTs) has been shown to be safe and effective in stem cell transplant recipients. However, the lack of virus-experienced T cells in donor cord blood (CB) has prevented the development of ex vivo expanded donor-derived VSTs for recipients of this stem cell source. Here we evaluated the feasibility and safety of ex vivo expansion of CB T cells from the 20% fraction of the CB unit in pediatric patients receiving a single CB transplant (CBT). In 2 clinical trials conducted at 2 separate sites, we manufactured CB-derived multivirus-specific T cells (CB-VSTs) targeting Epstein-Barr virus (EBV), adenovirus, and cytomegalovirus (CMV) for 18 (86%) of 21 patients demonstrating feasibility. Manufacturing for 2 CB-VSTs failed to meet lot release because of insufficient cell recovery, and there was 1 sterility breach during separation of the frozen 20% fraction. Delayed engraftment was not observed in patients who received the remaining 80% fraction for the primary CBT. There was no grade 3 to 4 acute graft-versus-host disease (GVHD) associated with the infusion of CB-VSTs. None of the 7 patients who received CB-VSTs as prophylaxis developed end-organ disease from CMV, EBV, or adenovirus. In 7 patients receiving CB-VSTs for viral reactivation or infection, only 1 patient developed end-organ viral disease, which was in an immune privileged site (CMV retinitis) and occurred after steroid therapy for GVHD. Finally, we demonstrated the long-term persistence of adoptively transferred CB-VSTs using T-cell receptor-Vß clonotype tracking, suggesting that CB-VSTs are a feasible addition to antiviral pharmacotherapy.

8.
Biol Blood Marrow Transplant ; 25(10): 2024-2030, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31201861

RESUMO

Pulmonary complications after hematopoietic cell transplantation (HCT) can lead to significant morbidity and mortality. Limited evaluation of the true incidence of these complications in children and subsequent outcomes of these complications have not been evaluated recently. In April 2018, the National Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; and the National Cancer Institute cosponsored a meeting of experts to describe the status of pulmonary complications in children after HCT, identify critical gaps in knowledge, and explore avenues for research to advance care and optimize outcomes. The Center for International Blood and Marrow Transplant Research was used to evaluate the cumulative incidence of pulmonary complications in children and their respective survival. Of the 5022 children included in this analysis who received allogeneic HCT from 2010 to 2016, 606 developed pulmonary complications within the first year after HCT. Pneumonitis occurred in 388 patients, 125 patients developed pulmonary hemorrhage, and 200 patients had lung graft-versus-host disease (GVHD). For those developing pulmonary complications within 1 year, overall survival 100 days after diagnosis of pulmonary complications was 49% (95% confidence interval [CI], 43% to 54%) for patients with pneumonitis, 23% (95% CI, 16% to 31%) in patients with pulmonary hemorrhage, and 87% (95% CI, 81% to 91%) in patients with pulmonary GVHD. This study demonstrates the approximate incidence of these complications, as well as their significant effects on survival, and can serve as a baseline for future research.

9.
Blood ; 133(7): 754-762, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30545834

RESUMO

Despite improvements, mortality after allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases remains a significant problem. We evaluated whether pre-HCT conditions defined by the HCT Comorbidity Index (HCT-CI) predict probability of posttransplant survival. Using the Center for International Blood and Marrow Transplant Research database, we identified 4083 patients with nonmalignant diseases transplanted between 2007 and 2014. Primary outcome was overall survival (OS) using the Kaplan-Meier method. Hazard ratios (HRs) were estimated by multivariable Cox regression models. Increasing HCT-CI scores translated to decreased 2-year OS of 82.7%, 80.3%, 74%, and 55.8% for patients with HCT-CI scores of 0, 1 to 2, 3 to 4, and ≥5, respectively, regardless of conditioning intensity. HCT-CI scores of 1 to 2 did not differ relative to scores of 0 (HR, 1.12 [95% CI, 0.93-1.34]), but HCT-CI of 3 to 4 and ≥5 posed significantly greater risks of mortality (HR, 1.33 [95% CI, 1.09-1.63]; and HR, 2.31 [95% CI, 1.79-2.96], respectively). The effect of HCT-CI differed by disease indication. Patients with acquired aplastic anemia, primary immune deficiencies, and congenital bone marrow failure syndromes with scores ≥3 had increased risk of death after HCT. However, higher HCT-CI scores among hemoglobinopathy patients did not increase mortality risk. In conclusion, this is the largest study to date reporting on patients with nonmalignant diseases demonstrating HCT-CI scores ≥3 that had inferior survival after HCT, except for patients with hemoglobinopathies. Our findings suggest that using the HCT-CI score, in addition to disease-specific factors, could be useful when developing treatment plans for nonmalignant diseases.


Assuntos
Anemia Aplástica/mortalidade , Doenças Autoimunes/mortalidade , Doenças da Medula Óssea/mortalidade , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Hemoglobinúria Paroxística/mortalidade , Doenças Metabólicas/mortalidade , Adolescente , Adulto , Anemia Aplástica/patologia , Anemia Aplástica/terapia , Doenças Autoimunes/patologia , Doenças Autoimunes/terapia , Doenças da Medula Óssea/patologia , Doenças da Medula Óssea/terapia , Criança , Pré-Escolar , Comorbidade , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Hemoglobinúria Paroxística/patologia , Hemoglobinúria Paroxística/terapia , Humanos , Lactente , Recém-Nascido , Masculino , Doenças Metabólicas/patologia , Doenças Metabólicas/terapia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
10.
Biol Blood Marrow Transplant ; 25(1): 157-162, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30144562

RESUMO

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a complication of hematopoietic stem cell transplant (HSCT) that causes severe multiorgan injury. The kidneys are almost universally affected. There is no proven therapy, but therapeutic plasma exchange (TPE) is commonly used to treat TA-TMA at Texas Children's Hospital (TCH). To date, there have been no studies assessing the long-term efficacy of TPE in preventing the development of chronic kidney disease (CKD) in TA-TMA patients. In this study we retrospectively analyzed the incidence of CKD in TA-TMA pediatric patients treated with TPE to determine if this treatment modality improves renal morbidity. We reviewed records between January 2007 and June 2017 of pediatric HSCT patients diagnosed with TA-TMA, identified through an internal database maintained at TCH. To be included patients must have completed a course of TPE per the "TPE in TA-TMA" institutional protocol at TCH. CKD was defined as kidney damage for at least 3 months and stratified into stages 1 through 5 according to estimated glomerular filtration rate. Stages 4 and 5 were considered "severe CKD." In the 10-year timeframe 15 patients with TA-TMA completed a course of TPE per our institutional protocol and were subsequently followed for a median of 963 days. Fourteen patients developed CKD, and 5 of these 14 patients developed severe CKD. The cumulative incidence of severe CKD development was 33% (95% confidence interval. 11% to 57%). 6 patients required dialysis, and 2 patients received a renal transplant. 5 patients received eculizumab in addition to TPE. In our patients a TPE course of at least 7 weeks (and up to 25 weeks) was not effective in the prevention of CKD. Our data indicate a need for alternative therapeutic measures to prevent the development of CKD in TA-TMA patients.


Assuntos
Taxa de Filtração Glomerular , Transplante de Células-Tronco Hematopoéticas , Troca Plasmática , Insuficiência Renal Crônica , Microangiopatias Trombóticas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/prevenção & controle , Estudos Retrospectivos , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/fisiopatologia , Microangiopatias Trombóticas/terapia
12.
Pediatr Blood Cancer ; 65(12): e27348, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30207052

RESUMO

BACKGROUND: After allogeneic hematopoietic stem cell transplantation (HSCT), patients have an increased susceptibility to infections, thought to be due in part to hypogammaglobulinemia. Thus, prophylactic administration of intravenous immunoglobulins (IVIG) has been administered to patients after HSCT as standard of care. This study compares the viral infection rate between dosing IVIG by IgG levels versus by routine monthly administration in pediatric patients after HSCT. PROCEDURE: In this retrospective chart review, we abstracted from electronic medical records data on pediatric patients undergoing HSCT from 2010 to 2012 for 6 months post-HSCT. We compared rates of infection between patients treated with routine IVIG prophylaxis and patients given IVIG prophylaxis based on IgG tough levels (IgG levels were checked every 2 weeks). RESULTS: Data were available and reviewed for 50 patients dosed with IVIG every 28 days (Group 1) and 100 patients dosed with IVIG based on IgG level > 400 mg/dl (Group 2). There was no significant difference in age (P = 0.98) or sex (P = 0.42), reason for HSCT, alemtuzumab use (P = 0.602), or reduced intensity conditioning (P = 1.00). Significantly more haploidentical donors were in Group 1 (P = 0.04), otherwise there was no significant difference in donor type between groups. Significantly less acute graft versus host disease occurred (P = <0.001) in Group 2 (P = <0.001). PCR documented viral infections were not significantly different (P = 0.412) (Table 1). Group 2 patients received significantly less IVIG (P < 0.001). CONCLUSION: Dosing IVIG to maintain an IgG level > 400 mg/dl is a cost-effective and safe way to prevent viral infections in pediatric patients undergoing HSCT.


Assuntos
Alemtuzumab/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Imunoglobulinas Intravenosas/administração & dosagem , Controle de Infecções , Condicionamento Pré-Transplante , Doença Aguda , Adolescente , Adulto , Fatores Etários , Aloenxertos , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/farmacocinética , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos
13.
Blood ; 132(17): 1737-1749, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30154114

RESUMO

The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD4+ and CD4+CD45RA+ cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD4+ cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune/imunologia , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/terapia , Genótipo , Humanos , Contagem de Linfócitos , Estudos Retrospectivos
14.
Pediatr Transplant ; 22(5): e13210, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29719098

RESUMO

Relapsed ALK-positive ALCL often is responsive to CRZ monotherapy. The subsequent role of allogeneic HCT after achieving second remission is poorly understood. We report 6 children who underwent allogeneic HCT for relapsed ALCL after CRZ. Age at transplant ranged from 10.7 to 22.6 years. Follow-up ranged from 0.9 to 4.5 years. All patients engrafted. Three of 4 patients that received a reduced-toxicity conditioning regimen containing fludarabine, alemtuzumab, and low-dose irradiation showed progressive mixed chimerism. Five patients remain in remission. One patient developed isolated CNS relapse 3.6 years after HCT despite a lack of previous CNS involvement. No acute transplant-related complications were experienced. One patient developed chronic renal disease secondary to transplant-associated microangiopathy and one patient chronic GVHD secondary to DLI. Ultimately, allogeneic HCT appears safe and potentially curative after remission induction with CRZ. The role of conditioning therapy, ablative or reduced intensity, remains uncertain for patients' post-CRZ monotherapy, and further studies may be warranted.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Anaplásico de Células Grandes/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Adolescente , Criança , Crizotinibe , Feminino , Humanos , Masculino , Recidiva , Transplante Homólogo , Adulto Jovem
15.
Blood ; 132(1): 89-100, 2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29632024

RESUMO

The HLH-2004 criteria are used to diagnose hemophagocytic lymphohistiocytosis (HLH), yet concern exists for their misapplication, resulting in suboptimal treatment of some patients. We sought to define the genomic spectrum and associated outcomes of a diverse cohort of children who met the HLH-2004 criteria. Genetic testing was performed clinically or through research-based whole-exome sequencing. Clinical metrics were analyzed with respect to genomic results. Of 122 subjects enrolled over the course of 17 years, 101 subjects received genetic testing. Biallelic familial HLH (fHLH) gene defects were identified in only 19 (19%) and correlated with presentation at younger than 1 year of age (P < .0001). Digenic fHLH variants were observed but lacked statistical support for disease association. In 28 (58%) of 48 subjects, research whole-exome sequencing analyses successfully identified likely molecular explanations, including underlying primary immunodeficiency diseases, dysregulated immune activation and proliferation disorders, and potentially novel genetic conditions. Two-thirds of patients identified by the HLH-2004 criteria had underlying etiologies for HLH, including genetic defects, autoimmunity, and malignancy. Overall survival was 45%, and increased mortality correlated with HLH triggered by infection or malignancy (P < .05). Differences in survival did not correlate with genetic profile or extent of therapy. HLH should be conceptualized as a phenotype of critical illness characterized by toxic activation of immune cells from different underlying mechanisms. In most patients with HLH, targeted sequencing of fHLH genes remains insufficient for identifying pathogenic mechanisms. Whole-exome sequencing, however, may identify specific therapeutic opportunities and affect hematopoietic stem cell transplantation options for these patients.


Assuntos
Testes Genéticos , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Linfo-Histiocitose Hemofagocítica/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lactente , Recém-Nascido , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Herança Multifatorial
16.
Biol Blood Marrow Transplant ; 24(8): 1643-1650, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29630926

RESUMO

There is a lack of consensus regarding the role and method of hematopoietic stem cell transplantation (HSCT) on patients with chronic granulomatous disease (CGD). Long-term follow-up after HSCT in these patient population is essential to know its potential complications and decide who will benefit the most from HSCT. We report the outcome of HSCT and long-term follow-up in 24 patients with CGD, transplanted in our center from either related (n = 6) or unrelated (n = 18) donors, over a 12-year period (2003 to 2015), using high-dose alemtuzumab in the preparative regimen. We evaluated the incidence and timing of adverse events and potential risk factors. We described in detailed the novel finding of increased autoimmunity after HSCT in patients with CGD. At a median follow-up of 1460 days, 22 patients were full donor chimeras, and 2 patients had stable mixed chimerism. All assessable patients showed normalization of their neutrophil oxidative burst test. None of the patients developed grades II to IV acute graft-versus-host disease, and no patient had chronic graft-versus-host disease. Twelve of 24 patients developed 17 autoimmune diseases (ADs). Severe ADs (cytopenia and neuropathy) occurred exclusively in the unrelated donor setting and mainly in the first year after HSCT, whereas thyroid AD occurred in the related donor setting as well and more than 3 years after HSCT. Two patients died due to infectious complications after developing autoimmune cytopenias. One additional patient suffered severe brain injury. The remaining 21 patients have long-term Lansky scores ≥ 80. The outcome of HSCT from unrelated donors is comparable with related donors but might carry an increased risk of developing severe AD. A lower dose of alemtuzumab may reduce this risk and should be tested in further studies.


Assuntos
Alemtuzumab/uso terapêutico , Doenças Autoimunes/etiologia , Doença Granulomatosa Crônica/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quimerismo , Seguimentos , Doença Granulomatosa Crônica/terapia , Síndrome de Guillain-Barré/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Pancitopenia/etiologia , Doadores não Relacionados
17.
Subst Abus ; 39(2): 199-205, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29522379

RESUMO

BACKGROUND: Despite high rates of chronic pain among their patients, opioid agonist treatment (OAT) counselors report an absence of training to manage chronic pain. METHODS: A multidisciplinary team developed a tailored training for counselors to screen and address chronic pain via a brief psychosocial intervention, and implemented it with 52 addiction counselors. Data on knowledge (9 true-false items) as well as attitudes, interest, and perceived ability (scored on 5-point Likert-type scales) were collected from counselors before (pre-test), after (post-test) training, and after 6 months (follow-up). RESULTS: Pre-test knowledge scores varied considerably. Compared to pre-test, mean counselor knowledge scores increased significantly post-training and at follow-up (p's.<05). The training was associated with increases in positive attitudes toward the role of counselors in managing chronic pain, interest in assessing chronic pain, and counselor ability to assess as well as suggest appropriate interventions for pain (all p's <.05). Perceived ability to assess chronic pain and suggest appropriate treatment interventions were higher at follow-up than at pre-test (p's <.05). CONCLUSIONS: Findings related to the initial evaluation of this training were promising, and future research is warranted to further examine the efficacy of training drug counselors on psychosocial interventions to manage chronic pain among OAT patients.


Assuntos
Dor Crônica/terapia , Conselheiros/educação , Conselheiros/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Manejo da Dor/psicologia , Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Feminino , Humanos , Masculino , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos , Manejo da Dor/métodos , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Psicoterapia/educação
18.
Biol Blood Marrow Transplant ; 24(7): 1424-1431, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29550628

RESUMO

Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed acute lymphoblastic leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T cell depletion used and, consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes among different donor types. One hundred and twenty-four pediatric patients underwent HSCT from a matched sibling donor (MSD; n = 48), an unrelated matched donor (UMD; n = 56), or a haploidentical donor (n = 20). We observed a similar 3-year event-free survival (EFS) for MSD recipients (of .64) and for UMD recipients (.62), but a significantly lower EFS for recipients of haploidentical transplants (.35; P = .01). Relapse was the main cause of HSCT failure and was significantly higher in the haploidentical donor group (.47 versus .19 for MSD and .24 for UMD; P = .02). Treatment-related mortality was evenly distributed among the donor groups (.17, .16, and .15 for the MSD, UMD, and haploidentical groups, respectively). Rates of infection-related mortality were lower than previously reported. Relapse is the main obstacle for successful HSCT in the contemporary era, and this effect is most evident in recipients of haploidentical donor grafts. Newer methods to improve graft-versus-leukemia effect are being evaluated and will need to be incorporated into the management of high-risk patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Criança , Pré-Escolar , Feminino , História do Século XXI , Humanos , Lactente , Recém-Nascido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
19.
Pediatr Transplant ; 22(3): e13141, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29388318

RESUMO

BK virus hemorrhagic cystitis is a complication of HCST. Response to IV cidofovir is unpredictable, and treatment carries risk of toxicity. We report the largest series of pediatric patients with BKHC after HSCT successfully treated with intravesicular cidofovir. There was no significant decrease in urine or plasma BK PCR. There was significant decrease in pain score on days 3 and 7, with associated decrease in morphine use. No patients experienced toxicities associated with IV cidofovir. Intravesicular cidofovir appears to be safe and effective for symptomatic treatment of BKHC in pediatric patients after HSCT.


Assuntos
Antivirais/administração & dosagem , Vírus BK , Cistite/tratamento farmacológico , Citosina/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Organofosfonatos/administração & dosagem , Infecções por Polyomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Administração Intravesical , Adolescente , Antivirais/uso terapêutico , Criança , Cidofovir , Cistite/etiologia , Citosina/administração & dosagem , Citosina/uso terapêutico , Feminino , Humanos , Masculino , Organofosfonatos/uso terapêutico , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia
20.
J Allergy Clin Immunol ; 141(3): 1036-1049.e5, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29241729

RESUMO

BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. METHODS: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. RESULTS: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. CONCLUSIONS: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.


Assuntos
Diabetes Mellitus Tipo 1/congênito , Diarreia , Fatores de Transcrição Forkhead , Doenças Genéticas Ligadas ao Cromossomo X , Transplante de Células-Tronco Hematopoéticas , Doenças do Sistema Imunitário/congênito , Imunossupressão , Mutação , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/terapia , Diarreia/genética , Diarreia/imunologia , Diarreia/mortalidade , Diarreia/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/mortalidade , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/mortalidade , Doenças do Sistema Imunitário/terapia , Lactente , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA