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1.
Pediatr Transplant ; 23(5): e13464, 2019 08.
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.

2.
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.

3.
Autophagy ; : 1-16, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30290719

RESUMO

Macroautophagy (autophagy) is an evolutionarily conserved recycling and stress response mechanism. Active at basal levels in eukaryotes, autophagy is upregulated under stress providing cells with building blocks such as amino acids. A lysosome-integrated sensor system composed of RRAG GTPases and MTOR complex 1 (MTORC1) regulates lysosome biogenesis and autophagy in response to amino acid availability. Stress-mediated inhibition of MTORC1 results in the dephosphorylation and nuclear translocation of the TFE/MITF family of transcriptional factors, and triggers an autophagy- and lysosomal-related gene transcription program. The role of family members TFEB and TFE3 have been studied in detail, but the importance of MITF proteins in autophagy regulation is not clear so far. Here we introduce for the first time a specific role for MITF in autophagy control that involves upregulation of MIR211. We show that, under stress conditions including starvation and MTOR inhibition, a MITF-MIR211 axis constitutes a novel feed-forward loop that controls autophagic activity in cells. Direct targeting of the MTORC2 component RICTOR by MIR211 led to the inhibition of the MTORC1 pathway, further stimulating MITF translocation to the nucleus and completing an autophagy amplification loop. In line with a ubiquitous function, MITF and MIR211 were co-expressed in all tested cell lines and human tissues, and the effects on autophagy were observed in a cell-type independent manner. Thus, our study provides direct evidence that MITF has rate-limiting and specific functions in autophagy regulation. Collectively, the MITF-MIR211 axis constitutes a novel and universal autophagy amplification system that sustains autophagic activity under stress conditions. Abbreviations: ACTB: actin beta; AKT: AKT serine/threonine kinase; AKT1S1/PRAS40: AKT1 substrate 1; AMPK: AMP-activated protein kinase; ATG: autophagy-related; BECN1: beclin 1; DEPTOR: DEP domain containing MTOR interacting protein; GABARAP: GABA type A receptor-associated protein; HIF1A: hypoxia inducible factor 1 subunit alpha; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPKAP1/SIN1: mitogen-activated protein kinase associated protein 1; MITF: melanogenesis associated transcription factor; MLST8: MTOR associated protein, LST8 homolog; MRE: miRNA response element; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; MTORC2: MTOR complex 2; PRR5/Protor 1: proline rich 5; PRR5L/Protor 2: proline rich 5 like; RACK1: receptor for activated C kinase 1; RPTOR: regulatory associated protein of MTOR complex 1; RICTOR: RPTOR independent companion of MTOR complex 2; RPS6KB/p70S6K: ribosomal protein S6 kinase; RT-qPCR: quantitative reverse transcription-polymerase chain reaction; SQSTM1: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TFE3: transcription factor binding to IGHM enhancer 3; TFEB: transcription factor EB; TSC1/2: TSC complex subunit 1/2; ULK1: unc-51 like autophagy activating kinase 1; UVRAG: UV radiation resistance associated; VIM: vimentin; VPS11: VPS11, CORVET/HOPS core subunit; VPS18: VPS18, CORVET/HOPS core subunit; WIPI1: WD repeat domain, phosphoinositide interacting 1.

4.
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
5.
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.

6.
Turk J Haematol ; 35(1): 12-18, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28404539

RESUMO

OBJECTIVE: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. MATERIALS AND METHODS: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with ß-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%). RESULTS: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all ß-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999. CONCLUSION: While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.


Assuntos
Talassemia/epidemiologia , Distribuição por Idade , Alelos , Demografia , Feminino , Humanos , Masculino , Programas de Rastreamento , Mutação , Fenótipo , Vigilância da População , Sistema de Registros , Talassemia/diagnóstico , Talassemia/prevenção & controle , Talassemia/terapia , Turquia/epidemiologia
7.
Clin Appl Thromb Hemost ; 24(6): 901-907, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29050499

RESUMO

Congenital factor deficiencies (CFDs) refer to inherited deficiency of coagulation factors in the blood. A total of 481 patients with CFDs, who were diagnosed and followed at our Pediatric Hematology and Oncology Clinic between 1990 and 2015, were retrospectively evaluated. Of the 481 cases, 134 (27.8%) were hemophilia A, 38 (7.9%) were hemophilia B, 57 (11.8%) were von Willebrand disease (vWD), and 252 (52.3%) were rare bleeding disorders (RBDs). The median age of the patients at the time of diagnosis and at the time of the study was 4.1 years (range: 2 months to 20.4 years) and 13.4 years (range: 7 months to 31.3 years), respectively. The median duration of the follow-up time was 6.8 years (range: 2.5 months to 24.8 years). One hundred nineteen (47.2%) of 252 patients with RBDs were asymptomatic, 49 (41.1%) of whom diagnosed by family histories, 65 (54.6%) through preoperative laboratory studies, and 5 (4.2%) after prolonged bleeding during surgeries. Consanguinity rate for the RBDs was 47.2%. Prophylactic treatment was initiated in 80 patients, 58 of whom were hemophilia A, 7 were hemophilia B, 13 were RBDs, and 2 were vWD. Significant advances have been achieved during the past 2 decades in the treatment of patients with CFDs, particularly in patients with hemophilias. The rarity and clinical heterogeneity of RBDs lead to significant diagnostic challenges and improper management. In this regard, multinational collaborative efforts are needed with the hope that can improve the management of patients with RBDs.


Assuntos
Transtornos de Proteínas de Coagulação/congênito , Transtornos de Proteínas de Coagulação/diagnóstico , Transtornos de Proteínas de Coagulação/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos
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.
J Forensic Sci ; 61(5): 1369-74, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27320825

RESUMO

Nicolau syndrome (NS) is a dermatological adverse reaction of intramuscular injections and is caused by several mechanisms. The etiopathogenesis remains unclear, and several hypotheses have suggested a vascular origin. Rhabdomyolysis (RM) is the destruction of striated muscle, with the subsequent release of muscle cell contents into circulation. NS and RM diagnoses may overlap. Herein, we present the autopsy findings of a 40-year-old female with NS complicated with RM. On clinical follow-up, creatine kinase (CK) was 7146 IU/L, and urea and creatinine levels were elevated on the third day after intramuscular diclofenac injection. Possible ischemic process triggered the RM and subsequent acute renal failure. The opportunity for an early diagnosis was missed because the patient delayed seeking medical aid. The prognosis worsened, and the patient died due to secondary sepsis. Early diagnosis of NS before the occurrence of complications is the most important issue in patient education and can be life-saving.


Assuntos
Síndrome de Nicolau/complicações , Rabdomiólise/complicações , Lesão Renal Aguda , Adulto , Autopsia , Creatina Quinase , Feminino , Humanos
11.
J Forensic Leg Med ; 39: 76-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26854854

RESUMO

Although cardiac injury is known to be the leading cause of death in electrocution, the differential diagnosis can be challenging in forensic practice since the exact mechanism is poorly understood and there is lack of reliable markers. Thus, death due to electrocution may be classified as a negative autopsy. The serum levels of and myocardial immunostaining loss for cardiac troponins and heart-type fatty acid binding protein (H-FABP) are highly sensitive and specific biomarkers of ischemic myocardial damage and may have a diagnostic value in determining the myocardial injury or the cause of death due to electrocution. Due to this reason, a rat model is prepared to investigate these issues. Thirty-two Wistar albino female rats were included and randomly divided into four groups of eight subjects. Group A was the control group, and Group B, C, and D were exposed to electrical current of 110 volt (V), 220 V, and 600 V, respectively. Blood samples and the hearts were collected from the rats for biochemical and immunostaining analyses. It is found that increased serum H-FABP levels were significantly associated with the higher voltage immediately after electrocution. However, serum cardiac troponin I (cTnI) levels did not show significant changes associated with the higher voltage in the early period of electrocution. As for histopathological examinations, the only significant difference in myocardial immunostaining loss was for H-FABP in Group B. Serum H-FABP levels may have a diagnostic value in the early postmortem period immediately after electrocution. Besides, it seems that serum H-FABP levels may be a better indicator than those of cTnI to reflect the myocardial damage in the early period of the electrocution.


Assuntos
Traumatismos por Eletricidade/diagnóstico , Proteínas de Ligação a Ácido Graxo/metabolismo , Troponina I/metabolismo , Animais , Biomarcadores/sangue , Proteína 3 Ligante de Ácido Graxo , Patologia Legal , Imuno-Histoquímica , Modelos Animais , Miocárdio/metabolismo , Ratos Wistar
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.
J Forensic Leg Med ; 38: 18-23, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26694873

RESUMO

As an opportunistic pathogen with high mortality rates, Cytomegalovirus (CMV) may lead to fatal disseminated CMV infection of the premature and newborn; thus necessitating the demonstration of CMV-DNA with clinical history and/or histopathological findings of CMV infection and defining other bacterial and viral infection agents with real-time polymerase chain reaction (RT-PCR) in udden unexpected death in infancy (SUDI) cases as we aimed in this study. 314 (144 female, 170 male) SUDI cases were prospectively investigated from January 2013 to January 2015 in Istanbul Forensic Medicine Institution. The study includes 87 tissue samples of 39 cases for post-mortem histopathological examination of interstitial pneumonia, myocarditis, meningitis, encephalitis, hepatitis, colitis or tubulointerstitial nephritis and/or accompanying chronic sialadenitis. CMV-DNA was found positive in 35 (40.2%) salivary gland, 19 (21.8%) lung, 1 (1.1%) tonsil, and 1 (1.1%) brain tissues. CMV sialadenitis and/or CMV pneumonia associated with other viral and/or bacterial agents were detected in 23 (60%) of 39 infant cases. The demonstration of CMV-DNA would significantly clarify the cause of death and collection of epidemiological data in SUDI cases with clinical history and histopathological findings of CMV infection accompanying chronic CMV sialadenitis. Furthermore, CMV suppresses the immune system, and may predispose to other bacterial and/or viral infections in these cases. Post-mortem molecular investigations are useful in explaining cause of death in SUDI with a suspicion of infection in forensic autopsies.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/genética , DNA Viral/isolamento & purificação , Morte Súbita do Lactente/etiologia , Encéfalo/virologia , Química Encefálica , Citomegalovirus/isolamento & purificação , Feminino , Patologia Legal , Humanos , Lactente , Recém-Nascido , Pulmão/química , Pulmão/microbiologia , Pulmão/virologia , Masculino , Miocardite/virologia , Tonsila Palatina/química , Tonsila Palatina/virologia , Pneumonia Bacteriana/diagnóstico , Pneumonia Viral/diagnóstico , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , Glândulas Salivares/química , Glândulas Salivares/virologia , Sialadenite/virologia , Vírus/genética , Vírus/isolamento & purificação
14.
Turk J Pediatr ; 57(2): 210-1, 2015 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26690610
15.
Case Rep Pediatr ; 2015: 537530, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26435870

RESUMO

Kasabach-Merritt phenomenon (KMP) is characterized by vascular tumour and consumptive coagulopathy with life-threatening thrombocytopenia, prolonged prothrombin time and partial thromboplastin time, hypofibrinogenemia, and the presence of high fibrin split products. We report a case of 3-year-old boy with local aggressive vascular lesions associated with KMP. Magnetic resonance imaging revealed an extensive lesion at paravertebral and retroperitoneal regions that was infiltrating vertebrae. Although we did not get any response to steroid or propranolol treatment, partial response was observed radiologically with interferon-alpha treatment. Unfortunately, the patient died because of the uncontrolled consumptive coagulopathy that led to intracranial hemorrhage which was caused by huge knee hematoma after minor trauma.

16.
17.
Turk J Haematol ; 32(2): 127-35, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26316480

RESUMO

OBJECTIVE: WNT5A is one of the most studied noncanonical WNT ligands and is shown to be deregulated in different tumor types. Our aim was to clarify whether hypermethylation might be the cause of low WNT5A mRNA levels and whether we could restore this downregulation by reversing the event. MATERIALS AND METHODS: The expression of WNT5A mRNA was studied in a large acute lymphoblastic leukemia (ALL) patient group (n=86) by quantitative real-time PCR. The methylation status was detected by methylation-specific PCR (MSPCR) and bisulphate sequencing. In order to determine whether methylation has a direct effect on WNT5A expression, disease-representative cell lines were treated by 5'-aza-20-deoxycytidine. RESULTS: Here we designed a validation experiment of the WNT5A gene, which was previously examined and found to be differentially expressed by microarray study in 31 T-cell ALL patients. The expression levels were confirmed by quantitative real-time PCR and the expression levels were significantly lower in T-cell ALL patients than in control thymic subsets (p=0.007). MSPCR revealed that 86% of the patients were hypermethylated in the WNT5A promoter region. Jurkat and RPMI cell lines were treated with 5'-aza-20-deoxycytidine and WNT5A mRNA expression was restored after treatment. CONCLUSION: According to our results, WNT5A hypermethylation does occur in ALL patients and it has a direct effect on mRNA expression. Our findings show that epigenetic changes of WNT signaling can play a role in ALL pathogenesis and reversing methylation might be useful as a possible treatment of leukemia.


Assuntos
Metilação de DNA , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Regiões Promotoras Genéticas/genética , Proteína Wnt-5a/genética , Adolescente , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Linhagem Celular Tumoral , Criança , Pré-Escolar , Decitabina , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Células Jurkat , Masculino , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Via de Sinalização Wnt/fisiologia , Proteína Wnt-5a/biossíntese , Proteína Wnt-5a/fisiologia
18.
Pediatr Hematol Oncol ; 32(7): 482-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26271020

RESUMO

In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.


Assuntos
Adrenomedulina/sangue , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Neutropenia Febril Induzida por Quimioterapia/sangue , Precursores de Proteínas/sangue , Adolescente , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Neutropenia Febril Induzida por Quimioterapia/mortalidade , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Taxa de Sobrevida
19.
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
20.
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
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