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1.
Pediatr Transplant ; 23(5): e13464, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31081274

RESUMO

IRIS is a phenomenon describing localized inflammatory reactions at BCG vaccination site and development of lymphadenopathy as immune system recovers. It is a rare entity in children following haploidentical HSCT. We represent the successful treatment of a case with fluctuating lymphadenopathy due to BCG vaccine during immune reconstitution period following ex vivo T-cell-depleted haploidentical HSCT.

4.
J Clin Immunol ; 39(1): 37-44, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30543054

RESUMO

PURPOSE: Human signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations present with a broad range of manifestations ranging from chronic mucocutaneous candidiasis and autoimmunity to combined immunodeficiency (CID). So far, there is very limited experience with hematopoietic stem cell transplantation (HSCT) as a therapeutic modality in this disorder. Here, we describe two patients with heterozygous STAT1 GOF mutations mimicking CID who were treated with HSCT. METHODS: Data on the HSC sources, conditioning regimen, graft-versus-host disease (GvHD) and antimicrobial prophylaxis, and the post-transplant course including engraftment, GvHD, transplant-related complications, infections, chimerism, and survival were evaluated. Pre- and post-transplant immunological studies included enumeration of circulating interferon gamma (IFN-γ)- and interleukin 17 (IL-17)-expressing CD4+ T cells and analysis of IFN-ß-induced STAT1 phosphorylation in patient 1 (P1)'s T cells. RESULTS: P1 was transplanted with cord blood from an HLA-identical sibling, and P2 with bone marrow from a fully matched unrelated donor using a reduced toxicity conditioning regimen. While P1 completely recovered from her disease, P2 suffered from systemic CMV disease and secondary graft failure and died due to severe pulmonary involvement and hemorrhage. The dysregulated IFN-γ production, suppressed IL-17 response, and enhanced STAT1 phosphorylation previously found in the CD4+ T cells of P1 were normalized following transplantation. CONCLUSION: HSCT could be an alternative and curative therapeutic option for selected STAT1 GOF mutant patients with progressive life-threatening disease unresponsive to conventional therapy. Morbidity and mortality-causing complications included secondary graft failure, infections, and bleeding.

5.
Pediatr Transplant ; 22(4): e13192, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29663666

RESUMO

T-cell-depleted HAPLO HSCT is an option to treat children with high-risk acute leukemia lacking an HLA-identical donor. We reviewed the outcome of children with acute leukemia after HAPLO (n = 21) and HLA-MUD (n = 32) transplantation. The proportion of patients with ≥CR2 was significantly higher in HAPLO transplantation than MUD transplantation. Patients with MUD transplantation were significantly higher ABO incompatible than patients with HAPLO transplantation. There was no difference between the 2 groups in terms of engraftment, aGvHD and cGvHD, VOD, hemorrhagic cystitis, infections, and relapse. The 5-year OS of MUD transplantation and HAPLO transplantation groups was found 65.8% and 71.1%, respectively (log-rank 0.51). The 5-year RFS was 80.7% for MUD transplantation group and 86.9% for HAPLO transplantation group (log-rank 0.48). There was no statistically significant difference between 2 groups according to TRM (25% MUD transplantation vs 16.3% HAPLO transplantation, log-rank 0.48). These data suggest that survival for patients with high-risk acute leukemia after HAPLO transplantation with ex vivo ɑß+ T-cell depletion is comparable with MUD transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante Haploidêntico/métodos , Doadores não Relacionados , Criança , Feminino , Seguimentos , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Procedimentos de Redução de Leucócitos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Risco , Linfócitos T , Resultado do Tratamento
6.
Med Mycol ; 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29608706

RESUMO

Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

7.
Leuk Lymphoma ; 59(1): 85-96, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28571522

RESUMO

We examined outcomes of 62 pediatric patients with relapsed or refractory non-Hodgkin lymphoma (rr-NHL) who underwent hematopoietic stem cell transplantation (HSCT). The overall survival (OS) and event-free survival (EFS) rates were 65% and 48%, respectively. Survival rates for patients with chemosensitive disease at the time of HSCT were significantly higher than those of patients with chemoresistant disease (69% vs. 37%, p = .019 for OS; 54% vs. 12%, p < .001 for EFS; respectively). A chemoresistant disease at transplantation was the only factor that predicted a limited OS (hazard ratio = 10.00) and EFS (hazard ratio = 16.39) rates. Intensive chemotherapy followed by HSCT could be an effective strategy for treating children with rr-NHL and may offer improved survival for a significant group of pediatric patients, particularly those with chemosensitive disease at transplantation.


Assuntos
Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Adolescente , Criança , Pré-Escolar , Resistencia a Medicamentos Antineoplásicos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/terapia , Masculino , Estadiamento de Neoplasias , Prognóstico , Recidiva , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Resultado do Tratamento , Turquia/epidemiologia
8.
Turk J Pediatr ; 60(5): 598-603, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30968645

RESUMO

Çakan M, Aktay-Ayaz N, Gemici H, Annayev A, Çitak A, Akçay A, Öztürk G. Sustained hyperferritinemia in a child with macrophage activation syndrome secondary to systemic juvenile idiopathic arthritis - perforinopathy: case based review. Turk J Pediatr 2018; 60: 598-603. Systemic juvenile idiopathic arthritis is a subtype of juvenile idiopathic arthritis and characterized by arthritis and many systemic features like fever, rash, hepatosplenomegaly, lymphadenopathy and serositis. Macrophage activation syndrome is the most dreadful complication of systemic juvenile idiopathic arthritis and can cause mortality and morbidity if not recognized and treated early and aggressively. Hemophagocytic lymphohistiocytosis (HLH) is characterized by diminished or absent activities of natural killer cells and cytotoxic T lymphocytes leading to cytokine storm and uncontrolled activation of T cells and macrophages. Primary (familial) HLH is a group of autosomal recessive disorders caused by mutations in the perforin and other related genes and distinctive for onset during early infancy and high rate of mortality. Secondary HLH may be caused by infectious, oncologic and rheumatologic disorders. The term Perforinopathy is used to describe cases with classical familial HLH and also for cases with familial HLH gene mutations but not following a classical familial HLH course. Herein we report a case of chronic perforinopathy in which clinical symptoms started with systemic juvenile idiopathic arthritis and severe macrophage activation syndrome that needed plasma exchange and extracorporeal membrane oxygenation during acute period and ongoing interleukin-1 blockage for sustained hyperferritinemia.


Assuntos
Artrite Juvenil/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Síndrome de Ativação Macrofágica/complicações , Criança , Citocinas , Oxigenação por Membrana Extracorpórea/métodos , Ferritinas/sangue , Humanos , Imunossupressores/uso terapêutico , Linfo-Histiocitose Hemofagocítica/diagnóstico , Síndrome de Ativação Macrofágica/diagnóstico , Masculino , Troca Plasmática/métodos
9.
J Pediatr Hematol Oncol ; 39(4): 249-253, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28267081

RESUMO

The aim of this study was to determine usefulness of measurements of maximal systolic velocity of the hepatic artery with Doppler ultrasonography in the diagnosis of venoocclusive disease (VOD) after hematopoietic stem cell transplantation. We prospectively obtained 5 sonograms per patient: pretransplantation, day +1, +7, +14, and +28 on 36 nonconsecutive children who underwent hematopoietic stem cell transplantation. We examined the hepatic artery, the portal, hepatic and splenic veins, the thickness of the gallbladder wall, the presence of ascites, and the liver and spleen size. The diagnosis of VOD was based on clinical and laboratory data. Patients were divided into 2 groups: those with VOD (n=18) and those without VOD (n=18). The variance of 2 groups was analyzed. Vmax of the hepatic artery had a strong correlation with clinical VOD diagnosis (P<0.001). There was no statistically significant difference in the other Doppler parameters. The results of our study showed that the measurement of Vmax of the hepatic artery can provide important support in the diagnosis of VOD and can be useful in the follow-up of treatment response.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Artéria Hepática/fisiopatologia , Hepatopatia Veno-Oclusiva/diagnóstico , Neoplasias/complicações , Adolescente , Velocidade do Fluxo Sanguíneo , Criança , Pré-Escolar , Feminino , Artéria Hepática/diagnóstico por imagem , Hepatopatia Veno-Oclusiva/diagnóstico por imagem , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Lactente , Masculino , Neoplasias/terapia , Ultrassonografia Doppler , Adulto Jovem
10.
Biol Blood Marrow Transplant ; 23(5): 790-794, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28192253

RESUMO

Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008. The median age of the patients' at the time of the transplantation was 8 years (range, 3 to 16 years) and the median age of the donors was 2 years (range, .5 to 6 years). The most common indication for HSCT was thalassemia major (42 of all patients, 80%). The stem cell source in all of the transplantations was bone marrow. In 37 of the transplantations, umbilical cord blood of the same donor was also used. In 50 of the 52 patients, full engraftment was achieved with a mean of 4.6 × 106 CD 34+ cells per kg of recipient weight. Ninety-six percent of the patients have been cured through hematopoietic stem cell transplantation without any complication. Primary engraftment failure was seen in only 2 patients with thalassemia major. All of the donors and the patients are alive with good health status. Preimplantation genetic diagnosis with HLA matching offers a life-saving chance for patients who need transplantation but lack an HLA genoidentical donor.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade/métodos , Diagnóstico Pré-Implantação , Talassemia beta/terapia , Adolescente , Transplante de Medula Óssea , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Feminino , Sobrevivência de Enxerto , Antígenos HLA/análise , Humanos , Gravidez , Irmãos , Doadores de Tecidos
11.
Turk J Haematol ; 33(4): 265-272, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27094103

RESUMO

OBJECTIVE: The prognostic factors and a new childhood prognostic index after autologous hematopoietic stem cell transplantation (AHSCT) in patients with relapsed/refractory Hodgkin's lymphoma (HL) were evaluated. MATERIALS AND METHODS: The prognostic factors of 61 patients who underwent AHSCT between January 1990 and December 2014 were evaluated. In addition, the Age-Adjusted International Prognostic Index and the Childhood International Prognostic Index (CIPI) were evaluated for their impact on prognosis. RESULTS: The median age of the 61 patients was 14.8 years (minimum-maximum: 5-20 years) at the time of AHSCT. There were single relapses in 28 patients, ≥2 relapses in eight patients, and refractory disease in 25 patients. The chemosensitivity/chemorefractory ratio was 36/25. No pretransplant radiotherapy, no remission at the time of transplantation, posttransplant white blood cell count over 10x103/µL, posttransplant positron emission tomography positivity at day 100, and serum albumin of <2.5 g/dL at diagnosis were correlated with progression-free survival. No remission at the time of transplantation, bone marrow positivity at diagnosis, and relapse after AHSCT were significant parameters for overall survival. CONCLUSION: The major factors affecting the progression-free and overall survival were clearly demonstrated. A CIPI that uses a lactate dehydrogenase level of 500 IU/L worked well for estimating the prognosis. We recommend AHSCT at first complete remission for relapsed cases, and it should also be taken into consideration for patients with high prognostic scores at diagnosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/epidemiologia , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Turquia/epidemiologia , Adulto Jovem
12.
Stem Cells Int ; 2016: 1641402, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26783400

RESUMO

This study evaluated the efficacy of mesenchymal stem cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. We report the first experience using MSCs to treat refractory aGVHD in 33 pediatric patients undergoing allogeneic HSCT from Turkey. Totally, 68 doses of bone marrow derived MSCs were infused. The median dose of MSC was 1.18 × 10(6) cells per kg body weight. Overall, complete response (CR) was documented in 18 patients, partial response (PR) was documented in 7 patients, and no response (NR) was documented in 8 patients. The 2-year estimated probability of overall survival (OS) for patients achieving CR and PR/NR was 63.8% and 29.4%, respectively (p = 0.0002). While the cumulative incidence of transplant related mortality (TRM) at day 100 after first MSC infusion was 46.6% in PR/NR patients, there was no any TRM at day 100 after first MSC infusion in CR patients (p = 0.001). Twelve patients developed chronic GVHD (cGVHD); eight of them were alive, with five having extensive disease and three having limited disease. In conclusion, MSCs appear to be safe and effective treatment option for pediatric patients with steroid refractory aGVHD. But the efficacy of MSCs on cGVHD in aGVHD patients treated with MSCs seems to be limited.

13.
Blood Coagul Fibrinolysis ; 27(6): 637-44, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26340456

RESUMO

The plasminogen (Plg) protein is the inactive proenzyme form of plasmin that dissolves fibrin thrombi by a process called fibrinolysis. It has been shown that homozygous or compound-heterozygous deficiency of this protein is a major cause of a rare inflammatory disease affecting mainly mucous membranes found in different body sites. In this study, five individual Turkish patients and nine Turkish families with type 1 Plg deficiency were investigated for PLG gene mutations. All of the coding regions of the PLG gene mutations were screened for mutations using denaturing high-pressure liquid chromatography (DHPLC). Samples showing a different DHPLC profile were subjected to DNA sequencing analysis. Here, we described five novel mutations namely, Cys49Ter, +1 IVS6 G>A, Gly218Val, Tyr283Cys, and Gly703Asp. Previously identified five nonsynonymous (Lys38Glu, Glu180Lys, Gly420Asp, Asp453Asn, Pro763Ser), five synonymous (330 C>T, 582 C>T, 771 T>C, 1083 A>G, 2286 T>G), and a 3' untranslated region (3' UTR) mutation (c.*45 A>G) were also reported in this present study. In this study, we have identified a total of eight mutations, five of which are novel. The mutations/polymorphisms identified in eight of the patients do not explain the disease phenotype. These cases probably carry other pathological mutations (homozygous or compound heterozygous) that cannot be detected by DHPLC.


Assuntos
Conjuntivite/genética , Hidrocefalia/genética , Mutação , Plasminogênio/deficiência , Plasminogênio/genética , Dermatopatias Genéticas/genética , Regiões 3' não Traduzidas , Cromatografia Líquida de Alta Pressão/métodos , Conjuntivite/sangue , Conjuntivite/complicações , Conjuntivite/diagnóstico , Feminino , Expressão Gênica , Heterozigoto , Homozigoto , Humanos , Hidrocefalia/sangue , Hidrocefalia/complicações , Hidrocefalia/diagnóstico , Masculino , Fases de Leitura Aberta , Fenótipo , Análise de Sequência de DNA , Dermatopatias Genéticas/sangue , Dermatopatias Genéticas/complicações , Dermatopatias Genéticas/diagnóstico , Turquia
14.
Turk J Pediatr ; 57(2): 210-1, 2015 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26690610
15.
Pediatr Transplant ; 19(7): 745-52, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26346042

RESUMO

This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty-nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU + etoposide + ara-C + melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow-up period of 39 months, 46 patients were alive. At five yr, the probabilities of OS, EFS, the relapse rate, and the non-relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at five yr was 72.3% and 19%, respectively (p < 0.001). Multivariate analysis showed that chemoresistant disease at the time of transplantation was the only factor predicting limited both OS (hazard ratio = 4.073) and EFS (hazard ratio = 4.599). AutoHSCT plays an important role for the treatment of rrHL in children and adolescents, and survival rates are better for patients with chemosensitive disease at the time of transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Adolescente , Criança , Feminino , Seguimentos , Doença de Hodgkin/mortalidade , Humanos , Masculino , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
16.
Pediatr Transplant ; 19(6): 645-51, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26156679

RESUMO

The ABO incompatibility between donor and recipient is not considered a barrier to successful allogeneic HSCT. Nevertheless, conflicting data still exist about the influence of ABO incompatibility on transplant outcome in pediatric patients with thalassemia. Fifty-one children with beta-thalassemia major who underwent allogeneic HSCT were enrolled this study. Twenty-three of them (45%) received an ABO-incompatible transplant [minor ABO mismatch: six (26%), major ABO mismatch: fourteen (61%), and bidirectional mismatch: three (13%)]. In this study, ABO incompatibility did not significantly impair GVHD, VOD, neutrophil and platelet engraftment, TRM, OS and TFS. Particularly in major and bidirectional ABO-mismatched patients, a delayed erythroid recovery was recorded as compared to the group receiving an ABO-compatible graft (median time, 31 and 38 days vs. 19.5 days; p: 0.02 and p: 0.03). Median time to red cell transfusion independence was significantly longer in major ABO-incompatible patients (median time, 87 days vs. 32 days; p: 0.001). Therefore, whenever feasible, major ABO-mismatched donors should be avoided in HSCT recipients, to prevent delayed erythroid recovery with prolonged RBC transfusion needs and impaired quality of life.


Assuntos
Sistema do Grupo Sanguíneo ABO/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Talassemia beta/terapia , Adolescente , Criança , Pré-Escolar , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Incidência , Lactente , Masculino , Cuidados Pós-Operatórios/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/métodos , Resultado do Tratamento , Talassemia beta/imunologia , Talassemia beta/mortalidade
17.
J Pediatr Hematol Oncol ; 37(7): 543-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26207778

RESUMO

Cytomegalovirus (CMV) infection is one of the most common complications after allogeneic hematopoietic stem cell transplantations (HSCT). Valganciclovir (VGC) has increasingly been used as prophylaxis against CMV infection after solid organ transplantation, but data on the efficacy and safety of VGC in pediatric HSCT patients are limited. We present our experience with VGC following ganciclovir (GCV) as preemptive therapy in pediatric HSCT patients. A total of 46 patients (38% patients) were found to be positive for CMV reactivation. Patients were treated with GCV (group I, n: 22) or GCV followed by VGC (GCV+VGC, group II, n: 24). VGC was preferred in the treatment of outpatients, whereas inpatients were treated with GCV. There was no significant difference in CMV clearance (P=0.78), treatment duration (P=0.087), and second CMV infection (P=0.3) between the 2 groups. The length of hospital stay was 21 days in GCV group, 14 days in VGC following GCV group (P=0.07). There were no treatment-related side effect in both groups. In conclusion, oral administration of VGC as preemptive therapy was found to be safe and effective. It is also a more suitable application for pediatric patients instead of an intravenous route. It could reduce the duration of inpatient stay and cost of hospitalization.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/fisiologia , Ganciclovir/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ativação Viral/efeitos dos fármacos , Administração Oral , Adolescente , Criança , Pré-Escolar , Feminino , Ganciclovir/administração & dosagem , Humanos , Lactente , Masculino , Estudos Retrospectivos , Valganciclovir
18.
Blood ; 126(16): 1885-92; quiz 1970, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26185129

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day +90) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken.


Assuntos
Ciclosporina/administração & dosagem , Rejeição de Enxerto , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Metotrexato/administração & dosagem , Neutropenia , Doadores não Relacionados , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade , Humanos , Incidência , Masculino , Oriente Médio , Neutropenia/congênito , Neutropenia/epidemiologia , Neutropenia/terapia , Estudos Retrospectivos , Sociedades Médicas
19.
Leuk Res ; 39(8): 906-12, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26111797

RESUMO

The MN1 (Meningioma 1) gene is overexpressed in certain subtypes of acute myeloid leukemia (AML) and high levels of MN1 expression in mouse bone marrow cells results in myeloid leukemia. We showed that compared with control bone marrow (BM) MN1 expression was increased (2-fold or more) in 29 out of 73 (40%) pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient BM. Additional analysis of MN1 expression in sub-groups within our cohort carrying different chromosome translocations showed that carriers of the good prognostic marker t(12;21)(TEL-AML1) (n=27) expressed significantly more MN1 than both healthy controls (n=9) (P=0.02) and the group carrying the t(9;22)(BCR-ABL) (n=9) (P=0.001). In addition, AML1 expression was also upregulated in 31 out of 45 (68%) B-ALL patient BM compared with control and there was a significant correlation between MN1 and AML1 expression (r=0.3552, P=0.0167). Retroviral MN1 overexpression increased the colony forming activity of mouse Pro-B/Pre-B cells in vitro. Our results suggest that deregulated MN1 expression contributes to the pathogenesis of pediatric B-ALL. Further investigation into the clinical and biological significance of elevated MN1 expression in TEL-AML1(positive) leukemia might provide insight into additional molecular mechanisms contributing to B-ALL and may lead to improved treatment options for patients.


Assuntos
Linfócitos B/fisiologia , Células da Medula Óssea/fisiologia , Células-Tronco Hematopoéticas/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Proteínas Supressoras de Tumor/genética , Adolescente , Animais , Células da Medula Óssea/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Criança , Pré-Escolar , Ensaio de Unidades Formadoras de Colônias , Feminino , Regulação Leucêmica da Expressão Gênica , Células-Tronco Hematopoéticas/metabolismo , Humanos , Lactente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cultura Primária de Células , Adulto Jovem
20.
Indian J Pediatr ; 82(5): 450-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25274444

RESUMO

OBJECTIVE: To determine outcome of neuroblastoma (NBL) in children under 18 mo of age who had been treated with national protocols. METHODS: The characteristics and treatment outcomes of 27 children were evaluated retrospectively. RESULTS: The event-free survival (EFS) at 60 and 108 mo were 84.7 % ± 7.7 and 72.6 % ± 7.7, respectively. The overall survival (OS) was 91.7 % ± 8 at 108 mo. The only significant risk factor for OS in children with neuroblastoma was the treatment response at the end of therapy (p = 0.001). "Wait and see" policy was applied to two infants with low risk NBL and one infant with stage 4S neuroblastoma and all 3 of these infants have been in remission at last followup. Four of the five patients with MYCN-amplified neuroblastoma were alive at a median follow-up time of 54 mo (range: 5-108 mo). CONCLUSIONS: The EFS and OS of the present group were similar to that of the previous series which included children under 18 mo of age with neuroblastoma. Well known prognostic factors did not affect EFS and OS significantly; this may be related to the retrospective design of the present study and the small number of patients reviewed. High survival rate in infants with MYCN-amplified tumors suggests the difference in the biology of infant neuroblastoma.


Assuntos
Neuroblastoma/diagnóstico , Intervalo Livre de Doença , Feminino , Seguimentos , Amplificação de Genes , Humanos , Lactente , Recém-Nascido , Masculino , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/genética , Neuroblastoma/mortalidade , Neuroblastoma/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
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