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1.
Pediatr Transplant ; : e13592, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587440

RESUMO

BACKGROUND: The objective of the study was to analyze the profile of infections in children with BMF following alloHCT. METHODS: Data of 169 consecutive children with inherited and acquired BMF treated with alloHCT between 2012 and 2017 in Polish pediatric transplant departments were analyzed in registry-based retrospective study, with respect to the type of infection, and clinical outcome. RESULTS: At least 1 infection was diagnosed in 107/169 patients (60.4%). In total, 182 infections were diagnosed. The most common were VI (96; 52.7%), followed by BI (71; 39.0%), and FI (15; 8.2%), P < .001. The most common etiological factors of VI were as follows: CMV (38.5%), EBV (22.9%), and BK virus (24%); while of BI were as follows: Staphylococcus spp. (17; 23.9%), Enterococcus faecium (10; 14.1%), and Klebsiella pneumoniae (9; 12.7%). No difference was found between the occurrence of infections with respect to donor type, graft source, and conditioning type. GvHD had no impact on the incidence of VI, BI, and FI. Fifteen FI were diagnosed in 12 patients, of which 14 FI were diagnosed in children transplanted for FA. Of total 107 children, 9 died (8.4%), of which 4 (3.7%) due to infections: bacterial sepsis (2) and invasive FI (2). CONCLUSION: Infections in children with BMF following alloHCT remain an important cause of morbidity. Children with FA had high incidence of FI. In our analysis, aGvHD had no impact on the occurrence on infections, although the study was not strong enough to prove such a difference.

2.
Mycoses ; 62(11): 990-998, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31429997

RESUMO

The objective of the study was the analysis of incidence and outcome of invasive fungal disease (IFD) in children treated for malignancy (PHO, paediatric hematology-oncology) or undergoing hematopoietic cell transplantation (HCT) over a period of six consecutive years in nationwide study. A total number of 5628 patients with newly diagnosed malignancies and 971 patients after HCT (741 allo-HCT and 230 auto-HCT) were screened for infectious complications in biennial reports. IFD incidence was lower among PHO patients: 8.8% vs 21.2% (P < .0001) and survival from IFD was better: 94.2% vs 84.1% (P < .0001). Auto-HCT patients had lower incidence (10.9% vs 24.4%) and lower mortality than allo-HCT patients. Introduction of national antifungal prophylaxis programme in HCT and acute leukaemia patients decreased incidence of IFD in HCT (from 23.1% to 13.4%) and AML on conventional chemotherapy (from 36% to 23%) but not in ALL patients during chemotherapy. In multivariate analysis, the incidence of IFD was higher in patients after HCT, diagnosed for ALL, AML or NHL, and in patients > 10 years old. Factors contributing to death with infection were as follows: undergoing HCT, diagnosis of acute leukaemia (ALL or AML) and duration of treatment of infection > 21 days. In conclusion, the incidence of IFD in allo-HCT and in AML patients on chemotherapy has decreased after introduction of national programme of antifungal prophylaxis, while the incidence of IFD in ALL patients on chemotherapy did not change significantly. The outcome of IFD both in PHO and HCT patients has largely improved in comparison with historical international data.

3.
Ann Hematol ; 98(9): 2197-2211, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321454

RESUMO

Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter cross-sectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; p < 0.0001). Infections with Gram-negative bacteria were more frequent than Gram-positives in adults (64.6% vs 44.8%; p < 0.0001). Outcome of bacterial infections was better in children (95.5% vs 91.4%; p = 0.0011). The IFD incidence (25.3% vs 6.3%; p < 0.0001) and outcome (88.0% vs 74.9%; p < 0.0001) were higher in children. The incidence of viral infections was higher in children after allo-HCT (56.3% vs 29.3%; p < 0.0001), and auto-HCT (6.6% vs 0.8%; p < 0.0001). Outcome of viral infections was better in children (98.6% vs 92.3%; p = 0.0096). Infection-related mortality was 7.8% in children and 18.4% in adults (p < 0.0001). No child after auto-HCT died of infection. Adult age, mismatched transplants, acute leukemia, chronic GVHD, CMV reactivation, infection with Gram-negatives, and duration of infection > 21 days were risk factors for death from infection. In conclusion, pediatric patients have 2.9-fold higher incidence and 2.5-fold better outcome of infections than adults after HCT.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas/epidemiologia , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Infecções Bacterianas/etiologia , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Infecções por Citomegalovirus/etiologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Lactente , Recém-Nascido , Infecções Fúngicas Invasivas/etiologia , Leucemia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
4.
Ann Transplant ; 24: 374-382, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31235684

RESUMO

BACKGROUND The objective of this study was the analysis of transplant outcomes and survival in children treated with allogeneic hematopoietic cell transplantation (alloHCT) for non-malignant disorders, with a focus on risk factor analysis of transplant-related mortality (TRM). MATERIAL AND METHODS The treatment outcome was analyzed retrospectively in 10 consecutive years in 4 pediatric transplant centers in Poland. To compare the outcomes, patient data were analyzed according to the diagnosis, age at transplant, donor type, stem cell source, conditioning regimens, transplanted CD34+ cells dose, and pediatric TRM score. RESULTS From 183 analyzed patients, 27 (14.8%) died, all of them due to transplant-related complications. TRM occurred more frequently in matched unrelated donor (MUD) transplant recipients vs. matched sibling donor (MSD) transplant recipients (p=0.02); in peripheral blood (PB) recipients vs. bone marrow (BM) recipients (p=0.004); and in patients receiving >5×106/kg CD34+ cells (p<0.0001). OS differed significantly according to underlying disease comparing to other diagnoses. Lower survival was found in patients transplanted from MUD (p=0.02). OS was higher in patients receiving BM (p=0.001) and in those receiving ≤5×106/kg CD34+ cells (p<0.001). Multivariate analysis showed lower probability of TRM in BM recipients (p=0.04). The probability of TRM was higher in SCID patients (p=0.02) and in patients receiving >5×106/kg CD34+ cells (p=0.0001). CONCLUSIONS Underlying disease, stem cell source, and CD34+ dose higher than 5×106/kg were the most important risk factors for TRM, and they all affected OS.

5.
J Allergy Clin Immunol ; 143(6): 2238-2253, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30660643

RESUMO

BACKGROUND: CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium species infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT). OBJECTIVE: We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics. METHODS: We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables' relevance with respect to survival and cure. RESULTS: Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 78.2%, 58.1%, and 72.3% 5 years after HSCT. Results were better in transplantations performed in 2000 or later and in children less than 10 years old at the time of HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT at 2 years or less from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC), and bone marrow-derived stem cells. Most rejections occurred after reduced-intensity or nonmyeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was 50% or greater donor in 85.2%. CONCLUSION: HSCT is curative in patients with CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS, and DFS. Prospective studies are required to compare the risks of HSCT with those of lifelong supportive therapy.

6.
Adv Clin Exp Med ; 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30462382

RESUMO

BACKGROUND: Acute kidney injury (AKI) occurs in up to 30% of pediatric intensive care unit (PICU) patients and is associated with a high mortality rate. OBJECTIVES: The objective of the study was to evaluate factors associated with the outcome and to identify the prognostic factors in children receiving continuous renal replacement therapy (CRRT). MATERIAL AND METHODS: This was a retrospective, single-center study, including 46 patients. RESULTS: Logistic regression analysis demonstrated significant effects on patient survival exerted by the percentage of fluid overload (FO%) (odds ratio (OR): 1.030; p = 0.044). In the group of patients with FO% < 25%, the mortality was 33.3%, and in the FO% ≥ 25% group, the mortality was 67.9% (p < 0.001). The probability of death without multi-organ failure (MOF) was 13%, while with MOF it was 74%. There was no difference in the duration of hospitalization between the CRRT patients (mean: 21.9 days) and the general population of children hospitalized in PICU in the same period (n = 3,255; mean: 25.4 days); however, a significant difference was noted in mortality between the 2 groups of patients (54% vs 6.5%; p < 0.001). CONCLUSIONS: The mortality of PICU CRRT patients is more than 8-fold higher than the mortality of the total PICU population. Coexisting MOF increases the mortality almost 6 times. The mortality of children with FO% ≥ 25% was more than 2-fold higher than the mortality of children with FO% < 25%.

7.
Transfus Apher Sci ; 57(3): 316-322, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29880247

RESUMO

The purpose of the survey was to evaluate the development and current use of hematopoietic stem cell transplantation (HSCT) in Poland between 1989-2016. The data for analysis (indication, number of performed HSCT, HSCT type, donor type, and stem cell source, year) have been collected annually using a standardized form. In Poland, between 1989-2016, the number of pediatric transplant beds grew from one to 40 and number and rate of transplants increased annually from 1/year (0.8/10 million) to 186/year (248/10 million). During the analyzed time period 2506 HSCTs were performed, including 1718 (68.6%) allogeneic transplants (allo-HSCT) with142 in 2016 and 788 (31.4%) autologous transplants (auto-HSCT) with 44 in 2016. Among 1718 allo-HSCT, 74% were performed for malignancy (ALL 47.2%, AML 26.2%, MDS 10.8%, CML 8.1%, NHL/HD 6.1%, others 2.5%), and 26% for non-malignant disorders (SAA 41%, congenital immunodeficiencies 35.4%, hereditary bone marrow failure 16%, metabolic disorders 7%). Among 788 auto-HSCTs, 30.8% were done for hematological malignancy (NHL 41.2%, AML 23.9%, HD 17.7%, ALL 15.6%, other 1.5%), while the remaining 69.2% for solid tumors (neuroblastoma 59.8%, Ewing's sarcoma 20.4%, other 19.8%). In Poland, between 1989-2016, the infrastructure indispensable to perform HSCT in every child with indication for this therapeutic procedure was created, and HSCT became an important part of pediatric treatment, especially in pediatric oncology, hematology, and in primary immunodeficiencies.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Criança , Feminino , Humanos , Masculino , Polônia
8.
Hum Immunol ; 79(6): 403-412, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29605688

RESUMO

Serious risks in unrelated hematopoietic stem cell transplantation (HSCT) including graft versus host disease (GvHD) and mortality are associated with HLA disparity between donor and recipient. The increased risks might be dependent on disparity in not-routinely-tested multiple polymorphisms in genetically dense MHC region, being organized in combinations of two extended MHC haplotypes (Ehp). We assessed the clinical role of donor-recipient Ehp disparity levels in N = 889 patients by the population-based detection of HLA allele phase mismatch. We found increased GvHD incidences and mortality rates with increasing Ehp mismatch level even with the same HLA mismatch level. In multivariate analysis HLA mismatch levels were excluded from models and Ehp disparity level remained independent prognostic factor for high grade acute GvHD (p = 0.000037, HR = 10.68, 95%CI 5.50-32.5) and extended chronic GvHD (p < 0.000001, HR = 15.51, CI95% 5.36-44.8). In group with single HLA mismatch, patients with double Ehp disparity had worse 5-year overall survival (45% vs. 56%, p = 0.00065, HR = 4.05, CI95% 1.69-9.71) and non-relapse mortality (40% vs. 31%, p = 0.00037, HR = 5.63, CI95% 2.04-15.5) than patients with single Ehp disparity. We conclude that Ehp-linked factors contribute to the high morbidity and mortality in recipients given HLA-mismatched unrelated transplant and Ehp matching should be considered in clinical HSCT.


Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Haplótipos/genética , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Histocompatibilidade , Adolescente , Adulto , Alelos , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Antígenos HLA/imunologia , Neoplasias Hematológicas/mortalidade , Humanos , Lactente , Isoantígenos/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
9.
Pediatr Transplant ; 22(3): e13158, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29396905

RESUMO

The aim of the study was to assess the risk of TRM in pediatric patients treated for malignant disorders with allogeneic HSCT, according to different risk factors. The treatment outcome was analyzed in 299 pediatric patients treated in pediatric transplant departments from 2006 to 2015. To compare the outcome, patients were analyzed all together and in groups according to the diagnosis, age at transplant, donor type, disease status, stem cell source, and pediatric TRM score. At the end of the observation time, 82 patients were alive, 82 died, of which 40 due to transplant-related reasons. The most frequently observed causes of TRM were toxic complications effecting with organ failure (38%), followed by infections (26%), PTLD (14.3%), and GvHD (16.7%). There was no statistical difference in the incidence of TRM depending on stem cell source (P = .209) and primary diagnosis (P = .301). According to TRM score, TRM was significantly higher in high-risk group (P = .006). High-risk patients had lower survival comparing to low/intermediate group (P = .0001). OS did not differ between ALL, AML, and MDS/JMML groups. The study confirmed the utility of factors included in TRM score stratification in assessing the risk of transplant procedure in pediatric patients transplanted for malignancies.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia/terapia , Linfoma/terapia , Síndromes Mielodisplásicas/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Leucemia/mortalidade , Linfoma/mortalidade , Masculino , Síndromes Mielodisplásicas/mortalidade , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Adulto Jovem
10.
J Ultrason ; 16(65): 204-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27446604

RESUMO

Infections in immunocompromised patients after hematopoietic stem cell transplantation can have a severe and atypical course. Some opportunistic pathogens are difficult to detect in microbiological tests, and that is why treatment success depends on an accurate clinical diagnosis. This article presents a case of a 7-year-old girl with severe aplastic anemia treated with bone marrow transplantation with post-transplantation period complicated by persistent, hectic fever, with peak episodes of 39-40°C, lasting several weeks. Repeated microbiological tests failed to reveal the etiological agent, and empirical anti-infective treatment was ineffective. In the fourth week of fever, imaging showed multiple foci resembling abscesses in the patient's internal organs and, subsequently, in soft tissues. The characteristics of these changes and data concerning environmental exposure led to the clinical diagnosis of cat scratch disease (bartonellosis) with multi-organ involvement and enabled the targeted treatment to be implemented. Fever subsided and organ lesions regressed. In this case, repeated ultrasound imaging was the basic diagnostic tool that helped arrive at a correct diagnosis and implement effective treatment of this life-threatening complication after hematopoietic stem cell transplantation.

12.
Cytokine ; 76(2): 182-186, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25982843

RESUMO

The present study aimed to assess the impact of the CXCL12 gene polymorphism (rs1801157) on clinical outcome of hematopoietic stem cell transplantation from unrelated donors. Toxic complications were less frequent among patients transplanted from donors carrying the CXCL12-3'-A allele (42/79 vs. 105/151, p=0.014 and 24/79 vs. 73/151, p=0.009, for grade II-IV and III-IV, respectively). Logistic regression analyses confirmed a role of donor A allele (OR=0.509, p=0.022 and OR=0.473, p=0.013 for grade II-IV and III-IV toxicity). In addition, age of recipients (OR=0.980, p=0.036 and OR=0.981, p=0.040, respectively) was independently protective while female to male transplantation and HLA compatibility were not significant. The incidence of aGvHD (grades I-IV) was lower in patients having A allele (52/119 vs. 113/204, p=0.043) and AA homozygous genotype (6/25 vs. 159/298, p=0.005). Independent associations of both genetic markers with a decreased risk of aGvHD were also seen in multivariate analyses (A allele: OR=0.591, p=0.030; AA homozygosity: OR=0.257, p=0.006) in which HLA compatibility seemed to play less protective role (p<0.1) while recipient age and donor-recipient gender relation were not significant. Moreover, CXCL12-3'-A-positive patients were less prone to early HHV-6 reactivation (2/34 vs. 19/69, p=0.026). The presence of the CXCL12-3'-A variant was found to facilitate outcome of unrelated HSCT.


Assuntos
Quimiocina CXCL12/genética , Transplante de Células-Tronco Hematopoéticas , Polimorfismo de Nucleotídeo Único , Doadores não Relacionados , Adolescente , Adulto , Fatores Etários , Alelos , Criança , Pré-Escolar , Feminino , Genótipo , Doença Enxerto-Hospedeiro/genética , Herpesvirus Humano 6/fisiologia , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Transplante Homólogo , Ativação Viral , Adulto Jovem
14.
Biol Blood Marrow Transplant ; 21(5): 829-39, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25617806

RESUMO

Some cancers treated with allogeneic hematopoietic stem cell transplantation (HSCT) are sensitive to natural killer cell (NK) reactivity. NK function depends on activating and inhibitory receptors and is modified by NK education/licensing effect and mediated by coexpression of inhibitory killer-cell immunoglobulin-like receptor (KIR) and its corresponding HLA I ligand. We assessed activating KIR (aKIR)-based HLA I-dependent education capacity in donor NKs in 285 patients with hematological malignancies after HSCT from unrelated donors. We found significantly adverse progression-free survival (PFS) and time to progression (TTP) in patients who received transplant from donors with NKs educated by C1:KIR2DS2/3, C2:KIR2DS1, or Bw4:KIR3DS1 pairs (for PFS: hazard ratio [HR], 1.70; P = .0020, Pcorr = .0039; HR, 1.54; P = .020, Pcorr = .039; HR, 1.51; P = .020, Pcorr = .040; and for TTP: HR, 1.82; P = .049, Pcorr = .096; HR, 1.72; P = .096, Pcorr = .18; and HR, 1.65; P = .11, Pcorr = .20, respectively). Reduced PFS and TTP were significantly dependent on the number of aKIR-based education systems in donors (HR, 1.36; P = .00031, Pcorr = .00062; and HR, 1.43; P = .019, Pcorr = .038). Furthermore, the PFS and TTP were strongly adverse in patients with missing HLA ligand cognate with educating aKIR-HLA pair in donor (HR, 3.25; P = .00022, Pcorr = .00045; and HR, 3.82; P = .027, Pcorr = .054). Together, these data suggest important qualitative and quantitative role of donor NK education via aKIR-cognate HLA ligand pairs in the outcome of HSCT. Avoiding the selection of transplant donors with high numbers of aKIR-HLA-based education systems, especially for recipients with missing cognate ligand, is advisable.


Assuntos
Efeito Enxerto vs Tumor/imunologia , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade Classe I/imunologia , Células Matadoras Naturais/imunologia , Receptores KIR/imunologia , Doadores não Relacionados , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Feminino , Efeito Enxerto vs Tumor/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Antígenos de Histocompatibilidade Classe I/genética , Teste de Histocompatibilidade , Humanos , Lactente , Células Matadoras Naturais/patologia , Masculino , Pessoa de Meia-Idade , Receptores KIR/genética
15.
Pediatr Transplant ; 19(2): E51-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25523867

RESUMO

NBS is a rare autosomal recessive congenital disorder associated with chromosome instability caused by a mutation in the NBN gene (8q21). Clinical manifestations include microcephaly, growth retardation, combined immunodeficiency, and a strong predisposition to develop (mainly lymphatic) malignancies. There is no specific treatment for patients with NBS, and the prognosis is generally poor. The therapeutic option for some patients with NBS may be HSCT. We present a case of safe and successful non-myeloablative UCB transplantation in the 19th month of the life of a female child with NBS concomitant with SCID.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Síndrome de Quebra de Nijmegen/terapia , Condicionamento Pré-Transplante , Pré-Escolar , Aberrações Cromossômicas , Feminino , Sangue Fetal/citologia , Genótipo , Humanos , Sistema Imunitário/fisiopatologia , Síndromes de Imunodeficiência/terapia , Mutação , Síndrome de Quebra de Nijmegen/imunologia , Reação em Cadeia da Polimerase , Doadores de Tecidos , Quimeras de Transplante
16.
Am J Hematol ; 89(10): E176-83, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25044365

RESUMO

Among cancers treated with allogeneic hematopoietic stem-cell transplantation (HSCT), some are sensitive to natural killer (NK) cell reactivity, described as the "missing self" recognition effect. However, this model disregarded the NK cell licensing effect, which highly increases the NK cell reactivity against tumor and is dependent on the coexpression of inhibitory killer cell immunoglobulin-like receptor (iKIR) and its corresponding HLA Class I ligand. We assessed clinical data, HLA and donor iKIR genotyping in 283 patients with myelo- and lymphoproliferative malignancies who underwent HSCT from unrelated donors. We found dramatically reduced overall survival (OS), progression free survival (PFS), and time to progression (TTP) among patients with malignant diseases with the lack of HLA ligand cognate with this iKIR involved in NK cell licensing in corresponding donor (events 83.3% vs. 39.8%, P = 0.0010; 91.6% vs. 47.7%, P = 0.00010; and 30.0% vs. 17.3%, P = 0.013, for OS, PFS, and TTP, respectively). The extremely adverse PFS have withstand the correction when patient group was restricted to HLA mismatched donor-recipient pairs. The incidence of aGvHD was comparable in two groups of patients. In malignant patients after HSCT the missing HLA ligand for iKIR involved in NK cell licensing in corresponding donor ("missing licensing proof") induced extremely adverse survival of the patients due to the progression of malignancy and not to the aGvHD. Avoiding the selection of HSCT donors with the "missing licensing proof" in the malignant patient is strongly advisable.


Assuntos
Seleção do Doador/métodos , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais , Neoplasias/terapia , Doadores não Relacionados , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Feminino , Genótipo , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Lactente , Masculino , Neoplasias/imunologia , Neoplasias/patologia , Receptores KIR/imunologia
17.
Contemp Oncol (Pozn) ; 18(1): 48-53, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24876821

RESUMO

AIM OF THE STUDY: Recent studies showed relatively better outcome for children with refractory (refAML) and relapsed acute myeloid leukemia (relAML). Treatment of these patients has not been unified within Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) so far. The goal of this study is to analyze the results of this therapy performed between 2005-2011. MATERIAL AND METHODS: The outcome data of 16 patients with refAML and 62 with relAML were analyzed retrospectively. Reinduction was usually based on idarubicine, fludarabine and cytarabine with allogenic hematopoietic stem cell transplant (alloHSCT) in 5 refAML and 30 relAML children. RESULTS: Seventy seven percent relAML patients entered second complete remission (CR2). Five-year OS and disease-free survival (DFS) were estimated at 16% and 30%. The outcome for patients after alloHSCT in CR2 (63%) was better than that of those not transplanted (36%) with 5-year OS of 34% vs. 2-year of 7% and 5-year DFS of 40% vs. 12.5%. Second complete remission achievement and alloHSCT were the most significant predictors of better prognosis (p = 0.000 and p = 0.024). The outcome of refAML children was significantly worse than relAML with first remission (CR1) rate of 33%, OS and DFS of 25% at 3 years and 53% at 2 years, respectively. All survivors of refAML were treated with alloHSCT after CR1. CONCLUSIONS: The uniform reinduction regimen of the documented efficacy and subsequent alloHSCT in remission is needed to improve the outcome for ref/relAML children treated within PPLLSG. The focus should be on the future risk-directed both front and second line AML therapy.

18.
Exp Hematol ; 42(4): 252-60, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24407162

RESUMO

Visfatin (VF) is an adipocytokine that performs many functions, including enhancing cell proliferation and biosynthesis of nicotinamide mononucleotides and dinucleotides. It also seems to be involved in the development of glucose metabolism disturbances. The goal of the study was the determination of VF concentrations in children with leukemia who are treated with stem cell transplantation. VF concentrations were measured in plasma before and after oral glucose tolerance test (OGTT; 60 and 120 minutes) in 22 children with leukemia treated with hematopoietic stem cell transplantation (HSCT) and healthy control subjects (n = 24). The HSCT group was studied twice: before HSCT (22 children) and approximately 6 months after HSCT (12 of 22 children). After fasting, concentrations of glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein, and high-sensitivity C-reactive protein (hsCRP) were determined. Significantly lower (p < 0.05) median values of VF concentrations at all time points in the OGTT were found in pre- HSCT children compared with control subjects. The median VF concentration was significantly higher after HSCT compared with before HSCT. The decrease in VF in leukemic children in complete remission may be caused by myelosuppression and immunosuppression after prolong chemotherapy and is beneficial because of the decrease in its antiapoptotic activity. VF can serve as an additional biochemical marker for remission in patients with leukemia. Normalization of plasma VF concentration after HSCT might be caused by a process of immune reconstitution and prolonged inflammation (e.g., infections, graft-versus-host disease), injury to organs (e.g., lungs, gut, liver), and endocrinology deficiencies.


Assuntos
Biomarcadores Tumorais/sangue , Citocinas/sangue , Transplante de Células-Tronco Hematopoéticas , Leucemia/sangue , Leucemia/terapia , Nicotinamida Fosforribosiltransferase/sangue , Adolescente , Adulto , Aloenxertos , Autoenxertos , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino
19.
Biol Blood Marrow Transplant ; 20(3): 409-14, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24345423

RESUMO

Three NOD2 polymorphisms (single nucleotide polymorphism [SNP]8 [2104C>T, Arg702Trp], SNP12 [2722G>C, Gly908Arg], and SNP13 [3020insC, Leu1007 fsins C]), identified as disease-associated variants in Crohn's disease, have recently been suggested as gene markers of the outcome of hematopoietic stem cell transplantation (HSCT). In the present multicenter study of 464 donor-recipient pairs, we focused on the effect of NOD2 mutation(s) on the risk of infections and acute graft-versus-host disease (aGVHD). The presence of SNP13 in recipients, donors, or both was more frequently seen in patients having sepsis than in those lacking sepsis (9 of 48 versus 33 of 386, P = .046). The presence of SNP8 (recipient and/or donor positive) was associated with a higher rate of Herpes viruses reactivation (17 of 21 versus 86 of 173, P = .007). In the SNP8-positive group, a trend for a higher rate of bacteremia well controlled by antibiotics was found (9 of 10 versus 47 of 81, P = .106). In contrast, the presence of SNP13 in recipient and/or donor resulted in a poor response to antibiotics (5 of 11 versus 9 of 10, P = .042). A statistically significant association between the presence of NOD2 SNPs and acute grade > II GVHD was found in a subgroup of HSCT patients who received transplants from unrelated donors with a myeloablative conditioning regimen that included antithymocyte globulin (ATG). In this subgroup of patients, donor positivity for any SNPs investigated (7 of 18 versus 17 of 113, P = .036) and, independently, only the presence of SNP8 (4 of 8 versus 20 of 123, P = .055) were associated with severe grade ≥ II aGVHD. In conclusion, SNP8 positivity in donors or recipients makes patients more prone to Herpes viruses reactivation and bacteremia but not to sepsis. Septic complications were associated with SNP13 polymorphism. SNP8 in donors constitutes a risk factor of severe aGVHD, but only if patients received transplants from unrelated donors and received ATG as part of a conditioning regimen.


Assuntos
Doença Enxerto-Hospedeiro/genética , Neoplasias Hematológicas/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Herpesviridae/genética , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo de Nucleotídeo Único , Sepse/genética , Doença Aguda , Adolescente , Adulto , Soro Antilinfocitário/uso terapêutico , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Infecções por Herpesviridae/etiologia , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Proteína Adaptadora de Sinalização NOD2/imunologia , Sepse/etiologia , Sepse/imunologia , Sepse/mortalidade , Índice de Gravidade de Doença , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Doadores não Relacionados
20.
Anticancer Res ; 32(11): 4749-53, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23155238

RESUMO

BACKGROUND: The chemokine-chemokine receptor (CR) network is involved in the regulation of cellular infiltration of tumours. Cancer cells and infiltrating macrophages produce a whole range of chemokines. This study explored the expression of some CR and chemokine production by cord blood stem cell-derived CD34(+) monocytes and their novel CD14(++)CD16(+) and CD14(+)CD16(-) subsets in response to tumour cells. MATERIAL AND METHODS: CR expression was determined by flow cytometry and their functional activity by migration to chemoattractants. Monocytes were cultured with tumour cells and the chemokine content was assessed in culture supernatants. RESULTS: CD14(++)CD16(+) monocytes exhibited increased expression of chemokine (C-C) receptor (CCR) 1, while CD14(+)CD16(-) of CCR2, chemokine (C-X-C) receptor (CXCR) 1, 2 and 4. The increased expression of CCR2 on CD14(+)CD16(-) monocytes was associated with their enhanced migration to monocyte chemoattractant protein-1 (CCL2), MCP-3 (CCL7), MCP-2 (CCL8) and MCP-4 (CCL13), while that of CXCR1 and 2 to interleukin 8 (CXCL8), and CXCR4 to stromal cell-derived factor-1 (CXCL12). Tumour cells induced production of macrophage inflammatory protein-1α (CCL3) MIP-1ß and regulated on activation normal T-cells expressed and secreted (CCL5) but not CCL2 or CXCL8, monokine induced by gamma interferon (CXCL9), interferon gamma-induced protein 10 (CXCL10). CONCLUSION: The studied monocyte subsets, in comparison to those from blood, exhibit different expression of CRs and response to the stimuli that occur from tumour cells.


Assuntos
Antígenos CD34/metabolismo , Quimiocinas/biossíntese , Monócitos/imunologia , Monócitos/metabolismo , Neoplasias/imunologia , Receptores de Quimiocinas/metabolismo , Comunicação Celular/imunologia , Linhagem Celular Tumoral , Quimiotaxia de Leucócito/imunologia , Sangue Fetal/citologia , Sangue Fetal/imunologia , Sangue Fetal/metabolismo , Citometria de Fluxo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Microambiente Tumoral/imunologia
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