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Background: Children undergoing allo-HCT are at high risk of EBV-related complications. The objective of the study was to analyze the impact of prophylactic post-transplant rituximab on EBV infection and EBV-PTLD in children after allo-HCT, to determine the risk factors for the development of EBV infection and EBV-PTLD and to determine their outcomes. Additionally, the impact of EBV-driven complications on transplant outcomes was analyzed. Methods: Single center retrospective analysis of EBV-related complications in pediatric population undergoing allo-HCT, based on strategy of prophylaxis with rituximab. Overall 276 consecutive children, including 122 on prophylaxis, were analyzed for EBV-driven complications and transplant outcomes. Results: Prophylaxis with rituximab resulted in significant reduction of EBV infection (from 35.1% to 20.5%; HR=2.7; p<0.0001), and EBV-PTLD (from 13.0% to 3.3%; HR=0.23; p=0.0045). A trend for improved survival was also observed (HR=0.66; p=0.068), while non-relapse mortality was comparable in both cohorts. The peak value of viral load was a risk factor in the development of EBV-PTLD: 10-fold higher peak viral load in comparison to the baseline 104 copies/mL, caused a 3-fold (HR=3.36; p<0.001) increase in the risk of EBV-PTLD. Rituximab treatment was effective as a preemptive therapy in 91.1%, and in 70.9% in EBV-PTLD. Patients who developed PTLD had dismal 5-year overall survival (29% vs 60%; p<0.001), and an increased risk of relapse (72% vs 35%; p=0.024). Conclusions: Rituximab for prophylaxis of EBV infection and EBV-PTLD was highly effective in pediatric population. Treatment of EBV-PTLD was successful in 70%, however the occurrence of EBV-PTLD was associated with an increased risk of relapse of primary malignant disease.
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Infecciones por Virus de Epstein-Barr , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4 , Rituximab , Trasplante Homólogo , Humanos , Rituximab/uso terapéutico , Rituximab/efectos adversos , Rituximab/administración & dosificación , Infecciones por Virus de Epstein-Barr/prevención & control , Infecciones por Virus de Epstein-Barr/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Niño , Femenino , Masculino , Preescolar , Estudios Retrospectivos , Adolescente , Herpesvirus Humano 4/inmunología , Lactante , Trasplante Homólogo/efectos adversos , Factores de Riesgo , Trastornos Linfoproliferativos/prevención & control , Trastornos Linfoproliferativos/etiología , Carga Viral , Resultado del TratamientoRESUMEN
Septic shock is a very rare manifestation of invasive fungal disease (IFD) in children after allogeneic hematopoietic cell transplantation (allo-HCT). The objective of this paper is analysis of two cases of pediatric patients with IFD caused by Saprochaete clavata after allo-HCT. Literature data on this infection in children and its outcome were also summarized. Infection with Saprochaete clavate presenting with symptoms of septic shock was being reported in 4 children, and 2 of them survived the infection. In conclusion, with quick diagnosis and quick treatment, the outcome of therapy of infection with Saprochaete clavata was successful.
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Trasplante de Células Madre Hematopoyéticas , Infecciones Fúngicas Invasoras , Saccharomycetales , Choque Séptico , Humanos , Niño , Choque Séptico/complicaciones , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Therapy results in pediatric Hodgkin lymphoma reflect remarkable progress in pediatric oncology. In the last decade, relevant development of new therapeutic options for children with refractory or relapsed disease has been made. In this study, we retrospectively analyzed therapy results and risk factors in children treated in a single oncology center according to five therapeutic protocols. Data from 114 children treated by a single institution between 1997 and 2022 were analyzed. Classic Hodgkin lymphoma therapy results were divided into four therapeutic periods: 1997-2009, 2009-2014, 2014-2019, and 2019-2022. For nodular lymphocyte-predominant Hodgkin lymphoma, data from one therapeutic protocol was analyzed. For the entire group, the 5-year probability of overall survival was 93.5%. There were no statistically significant differences between therapeutic periods. The occurrence of B symptoms at diagnosis and incidence of relapse were risk factors for death (p = 0.018 and p < 0.001). Relapse occurred in 5 cases. The 5-year probability of relapse-free survival for the entire group was 95.2%, without significant differences between groups. Patients treated between 1997 and 2009 had over a sixfold higher risk for events, defined as primary progression, relapse, death, or incidence of secondary malignancies (OR = 6.25, p = 0.086). The 5-year probability of event-free survival for all patients was 91.3%. Five patients died, and the most common cause of death was relapse. Modern therapeutic protocols in pediatric Hodgkin lymphoma are marked by excellent outcomes. Patients with disease relapses have a notably high risk of death, and the development of new therapeutic options for this group remains one of the main goals of current trials.
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Enfermedad de Hodgkin , Humanos , Niño , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/tratamiento farmacológico , Supervivencia sin Enfermedad , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is a cutaneous form of chronic active Epstein-Barrvirus (EBV) infection, which can develop into the extremely rare systemic lymphoma. Patients with Inborn errors of immunity (IEI), such as common variable immunodeficiency (CVID), are at higher risk of developing a severe course of infections especially viral and malignancies than the general population. The aim of the study was to present complex diagnostic and therapeutic management of HV-LPD. The clinical diagnosis was confirmed at the histological and molecular level with next generation sequencing. HV-LPD was diagnosed in a patient with CVID and chronic active Epstein-Barr virus (CAEBV) infection. The patient was refractory to CHOP chemotherapy and immunosuppressive treatment in combination with antiviral drugs (prednisone, bortezomib, gancyclovir). The third-party donor EBV-specific cytotoxic T cells (EBV-CTL, tabelecleucel) were used, which stabilised the disease course. Finally, matched unrelated donor hematopoietic cell transplantation (MUD-HCT) was performed followed by another cycle of EBV-CTL.
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Inmunodeficiencia Variable Común , Infecciones por Virus de Epstein-Barr , Hidroa Vacciniforme , Trastornos Linfoproliferativos , Neoplasias Cutáneas , Niño , Inmunodeficiencia Variable Común/complicaciones , Inmunodeficiencia Variable Común/terapia , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/terapia , Herpesvirus Humano 4 , Humanos , Hidroa Vacciniforme/diagnóstico , Hidroa Vacciniforme/terapia , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/terapiaRESUMEN
BACKGROUND/AIM: Cytomegalovirus (CMV) infection is one of the major causes of morbidity following hematopoietic cell transplantation (HCT). Allogeneic HCT (allo-HCT) recipients are at the highest risk of clinically significant CMV reactivation. While letermovir has been approved for prophylactic use in CMV seropositive adults, reports on pediatric data are very limited. The objective of the study was to examine the use of letermovir for prophylaxis from CMV infection in children undergoing allo-HCT in a single center. PATIENTS AND METHODS: This retrospective matched-pair analysis study included 39 CMV-seropositive pediatric patients undergoing allo-HCT receiving letermovir as a primary prophylaxis for CMV infection on a compassionate-use basis (LMV group, n=13) or not (control group, n=26). There were no differences in basic characteristics between the analyzed groups. Among patients of the study group, 12 received primary prophylaxis with letermovir from day +1 after HCT. One patient, previously treated with ganciclovir received secondary prophylaxis from day +18. RESULTS: Prophylactic dose of letermovir was adjusted to cyclosporine co-administration, varied in between 120-480 mg, and given orally, once daily. No CMV reactivation was observed during administration of letermovir. Cumulative incidence of CMV reactivation was significantly higher for the control group not receiving prophylaxis. Of the 13 patients of the study group, three died; however, deaths were not attributable to CMV infection. We did not observe any toxicities related to letermovir. CONCLUSION: Our data support letermovir prophylaxis efficacy and safety in pediatric patients after allo-HCT. Compared with the historical group, prophylactic use of letermovir decreased the number of CMV reactivations in children.
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Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Acetatos/uso terapéutico , Adulto , Niño , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Quinazolinas , Estudios RetrospectivosRESUMEN
Duchenne muscular dystrophy (DMD), caused by a mutation in the DMD gene, is known to be associated with co-morbidities including cardiomyopathy, respiratory failure, neuromuscular scoliosis and intellectual disability. Animal studies have explored the susceptibility of dystrophin-deficient mice with the development of myogenic tumors. While there is adequate literature describing both DMD and rhabdomyosarcoma (RMS) separately, there has yet to be a comprehensive literature review investigating the possibility that patients with DMD may be at a higher risk of developing RMS and other myogenic tumors. We present the case of a pediatric patient with DMD who developed alveolar RMS and review the literature for susceptibility to development of myogenic tumors in cases of DMD gene mutation.
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BACKGROUND/AIM: Comparison of transplant outcomes in long-term follow-up of children after total body irradiation (TBI)- or chemotherapy-based conditioning allogeneic hematopoietic cell transplantation (allo-HCT). PATIENTS AND METHODS: Patients undergoing allo-HCT for Acute lymphoblastic leukemia (ALL) conditioned either with TBI (n=55) or chemotherapy (n=84) were compared. The following transplant outcomes were analyzed: overall survival (OS), event-free survival (EFS), relapse incidence (RI), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS). RESULTS: All analyzed long-term transplant outcomes were significantly better for patients conditioned with TBI at 2 years after transplant. OS at 2 years was 84% after TBI and 60.5% after chemotherapy-conditioning (p=0.005). Risk factor analysis showed that two factors, TBI-based conditioning and transplant in first remission of ALL, significantly improved OS, EFS, GRFS, and decreased RI. CONCLUSION: TBI-based conditioning before allogeneic HCT in children with acute lymphoblastic leukemia provides significantly better transplant outcomes, when compared to chemotherapy-based conditioning.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Supervivencia sin Enfermedad , Enfermedad Injerto contra Huésped/etiología , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Irradiación Corporal TotalRESUMEN
BACKGROUND: Neuroblastoma is the most common pediatric extracranial tumor with varied prognoses, but the survival of treated refractory or relapsing patients remains poor. OBJECTIVE: This analysis presents the outcomes of children with neuroblastoma undergoing MIBG therapy in Poland in 2006-2019. STUDY DESIGN: A retrospective cohort of 55 patients with refractory or relapsed neuroblastoma treated with I-131 MIBG in Poland in 2006-2019 was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of second cancers and CI of hypothyroidism. Survival curves were estimated using the Kaplan-Meier method and compared between the cohorts by the log-rank test. Cox modeling was adopted to estimate hazard ratios for OS and EFS, considering factors with P < 0.2. RESULTS: Fifty-five patients with a median age of 78.4 months (range 18-193) with neuroblastoma underwent one or more (4 patients) courses of MIBG I-131 therapy. Fifteen patients were not administered chemotherapy, 3 children received standard-dose chemotherapy, and 37 patients were administered high-dose chemotherapy (HDCT) (busulfan-melphalan in 24 and treosulfan-based in 12 patients). Forty-six patients underwent stem cell transplantation, with autologous (35 patients), haploidentical (6), allogeneic (4), and syngeneic grafts (1). The median time from first MIBG therapy to SCT was 22 days. Children with relapsing tumors had inferior OS compared to those with primary resistant disease (21.2% vs 58.7%, p=0.0045). Survival was better in patients without MYCN gene amplification. MIBG therapy was never curative, except in patients further treated with HDCT with stem cell rescue irrespective of the donor type. 31 patients were referred for immune therapy after MIBG therapy, and the 5-year OS in this group was superior to the untreated children (55.2% vs 32.7%, p=0.003), but the difference in the 5-year EFS was not significant (25.6% vs 32.9%, p=ns). In 3 patients, a second malignancy was diagnosed. In 19.6% of treated children, hypothyroidism was diagnosed within 5 years after MIBG therapy. CONCLUSION: MIBG therapy can be incorporated into the therapeutic strategy of relapsed or resistant neuroblastoma patients as preconditioning with HDCT rather than stand-alone therapy. Follow-up is required due to the incidence of thyroid failure and risk of second cancers.
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BACKGROUND: Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and treatment of this complication is one of the utmost priorities of supportive therapy during transplant procedure. The objective of this study was the analysis of the influence of palifermin, keratinocyte growth factor (KGF), on transplant outcomes in patients undergoing allo-HCT. PATIENTS AND METHODS: A total of 253 allo-HCTs performed between 2003-2018 in patients aged 0-19 years at a single center were analyzed. KGF was administered in 161 HCTs. Uni- and multivariate risk factor analyses were performed. RESULTS: In spite of reducing the duration and grade of mucositis, no prognostic impact of KGF was shown for overall survival, event-free survival, relapse incidence, acute and chronic graft-versus-host disease (GVHD), nor GVHD-free relapse-free survival. CONCLUSION: Palifermin had no impact on transplant outcomes in children and adolescents undergoing allo-HCT.
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Factor 7 de Crecimiento de Fibroblastos/administración & dosificación , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Células Madre Hematopoyéticas/efectos de los fármacos , Estomatitis/terapia , Adolescente , Adulto , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Supervivencia sin Progresión , Estomatitis/complicaciones , Estomatitis/patología , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
High-dose chemotherapy with autologous hematopoietic stem cell transplantation improves event-free survival in patients with high-risk neuroblastoma. However, in heavily pretreated patients, poor marrow function can be an obstacle in the successful proceeding of therapy. Priming with plerixafor plus filgrastim is an option for effective mobilization and collection of stem cells. In addition, thrombopoietin agonist eltrombopag can improve the outcome of posttransplantation thrombocytopenia and poor graft function in the posttransplant setting. We describe a case of a child with high-risk neuroblastoma, for whom plerixafor and eltrombopag were used as an effective and safe supportive therapy.
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Fármacos Anti-VIH/uso terapéutico , Benzoatos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Compuestos Heterocíclicos/uso terapéutico , Hidrazinas/uso terapéutico , Neuroblastoma/terapia , Pirazoles/uso terapéutico , Bencilaminas , Preescolar , Terapia Combinada , Ciclamas , Quimioterapia Combinada , Femenino , Humanos , Neuroblastoma/patología , PronósticoRESUMEN
Patients with Nijmegen breakage syndrome (NBS) can develop life-threatening immunodeficiency, which should be treated with hematopoietic stem cell transplantation (HSCT). We report the case of a 14-year-old girl with NBS who due to an increasing number of severe complications was referred for HSCT from a matched unrelated donor. After reduced-intensity conditioning and transplantation of peripheral blood hematopoietic cells, during the early post-transplant period (days 0-30), the girl suffered from severe mucositis, fever episodes, mild acute renal injury and facial vasculitis. All these complications were managed successfully. During the intermediate post-transplant period (days 30-100) a number of hepatic and gastrointestinal complications occurred, including cholecystitis, cholelithiasis with choledocholithiasis, pancreatitis as well as acute bleeding from the lower gastrointestinal tract caused by rectal and recto-sigmoid junction ulcers. All the obstacles were obviously attributable both to the primary congenital disease, its complications, and transplantation itself. We overcame these complications and treated the patient with the best possible and safe methods. The multidisciplinary approach based on combined surgical, endoscopic and conservative management of multiple post-transplant complications was successful for the patient.
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BACKGROUND: A retrospective analysis was performed to investigate the survival outcomes in pediatric acute lymphoblastic leukemia (ALL) based on time period. We hypothesized that improvement has been obtained with the time-dependent therapeutic era and rise in the gross domestic product (GDP) and Human Development Index (HDI). MATERIALS AND METHODS: Data from 710 children who were treated for ALL between 1958 and 2018 at a single pediatric center were analyzed for probability of 5-year overall survival (pOS), event-free survival (pEFS) and relapse risk (pRR). Time periods were defined by the treatment protocols used in seven consecutive therapeutic eras. RESULTS: Over the 60-year period analyzed, pOS increased from 1.2% to 90.7%, pEFS from 1.2% to 86.6%, and pRR decreased from 98.8% to 9.9% for patients treated in the past decade. Risk of mortality for patients who received chemotherapy and hematopoietic cell transplant was reduced to 9.9% in the recent era, however, no statistically significant survival difference was found between patients treated with stem cell transplant and those not. CONCLUSION: The therapeutic era, related to improved GDP and HDI, was a statistically significant predictor of increased OS from ALL.
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Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Adolescente , Biomarcadores de Tumor , Biopsia , Niño , Preescolar , Femenino , Encuestas de Atención de la Salud , Humanos , Lactante , Recién Nacido , Masculino , Evaluación de Resultado en la Atención de Salud , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
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.
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Anemia Aplásica/cirugía , Síndromes Congénitos de Insuficiencia de la Médula Ósea/cirugía , Enfermedad Injerto contra Huésped/mortalidad , Enfermedad Granulomatosa Crónica/cirugía , Trasplante de Células Madre Hematopoyéticas/mortalidad , Enfermedades de Inmunodeficiencia Primaria/cirugía , Adolescente , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: Immune recovery is a key factor in the management of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study analyzed the factors contributing to immune reconstitution after allo-HSCT. PATIENTS AND METHODS: Overall, 65 children with malignant or non-malignant diseases were included in multivariate analyses. RESULTS: The following factors contributed to a faster immune recovery: peripheral blood as a stem cell source and reactivation of CMV infection for CD3+ and CD4+ lymphocyte subpopulations; reactivation of CMV infection for CD8+ subset; donor EBV-IgG+ and no EBV reactivation for CD19 lymphocytes; recipient age below 10 years and peripheral blood as a stem cell source for NK cells. For CD2 and CD4/CD8 ratio no factor was significant in multivariate analysis. CONCLUSION: Patients receiving a graft from an EBV-IgG-positive donor and not having early EBV post-transplant viremia show faster recovery of the B-cells, while patients with early CMV-DNA-emia have a better re-establishment of T-cell subsets.
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Infecciones por Citomegalovirus/virología , Citomegalovirus/inmunología , Infecciones por Virus de Epstein-Barr/virología , Neoplasias Hematológicas/inmunología , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4/inmunología , Subgrupos Linfocitarios/inmunología , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/virología , Humanos , Lactante , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Células Asesinas Naturales/virología , Subgrupos Linfocitarios/patología , Subgrupos Linfocitarios/virología , Masculino , Pronóstico , Trasplante Homólogo , Activación ViralRESUMEN
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.
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Trasplante de Células Madre Hematopoyéticas/mortalidad , Leucemia/terapia , Linfoma/terapia , Síndromes Mielodisplásicos/terapia , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Leucemia/mortalidad , Linfoma/mortalidad , Masculino , Síndromes Mielodisplásicos/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo , Adulto JovenRESUMEN
The aim of the study was to extend the potential use of human stem cells isolated from amniotic fluid in medical applications by confirming their high homogeneity and quality. Amniotic fluid samples were collected during amniocentesis from 165 women during pregnancy. The proliferation rate, clonogenicity, karyotype, aging process, pluripotent cell markers, expression of surface markers, and the potential to differentiate into adipose, bone and cartilage cells of hAFSCs were analyzed. Obtained results revealed that mesenchymal stem cells could be derived successfully from amniotic fluid, which exhibit properties comparable with MSCs of other origins. It is the first study, in which such a large group of patients was involved. Comprehensive statistical and biological analysis were conducted some of which clearly being innovative in relation to human amniotic fluid-derived stem cells. J. Cell. Biochem. 118: 116-126, 2017. © 2016 Wiley Periodicals, Inc.
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Líquido Amniótico , Separación Celular/métodos , Células Madre Pluripotentes , Adolescente , Adulto , Líquido Amniótico/citología , Líquido Amniótico/metabolismo , Antígenos de Diferenciación/biosíntesis , Proliferación Celular/fisiología , Separación Celular/normas , Senescencia Celular/fisiología , Femenino , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/metabolismo , EmbarazoRESUMEN
The objective of this study was to evaluate complex biological properties of human stem cells isolated from adipose tissue (ASCs) harvested utilizing different methods: surgical resection (R), power-assisted liposuction (PAL), and laser-assisted liposuction (LAL). ASCs were isolated from healthy donors, due to surgical resection, power-, and laser-assisted liposuction. Isolated cells were characterized by their clonogenicity, proliferation rate, doubling time, multilineage differentiation, and senescence potential. The average number of ASCs from 1g/1 ml of solid adipose tissue/lipoaspirate was 2.9 × 105 ± 2.4 × 105 , 1.1 × 105 ± 0.8 × 105 , and 1.2 × 105 ± 0.7 × 105 , respectively, for ASCsR, ASCsPAL, and ASCsLAL. However, number of colonies formed by ASCsR and ASCsPAL was significantly higher compared to the average number of colonies formed by ASCsLAL. Also, in comparison to other analyzed cell groups, ASCsPAL obtained the highest proliferative activity. All analyzed cells were characterized by stable expression of CD90 and CD44 markers during prolonged culture. Expression of CD34 and CD45 markers was decreasing in subsequent passages. Presented study shows that different ASCs collection method affects some basic characteristics of these cells, such as number of isolated cells, clonogeneity, or doubling time. J. Cell. Biochem. 118: 1097-1107, 2017. © 2016 Wiley Periodicals, Inc.
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Adipocitos/citología , Tejido Adiposo/cirugía , Lipectomía/métodos , Manejo de Especímenes/métodos , Células Madre/citología , Tejido Adiposo/citología , Recuento de Células , Diferenciación Celular , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Femenino , Voluntarios Sanos , HumanosRESUMEN
Acute lymphoblastic leukemia (ALL) is the most frequent pediatric malignancy. The chemotherapy for ALL is associated with a profound secondary immune deficiency.We evaluated the number and phenotype of natural killer (NK) cells at diagnosis, after the intensive chemotherapy and following the completion of the entire treatment for patients with ALL. The fraction, absolute number, and percentage of NK cells expressing interferon-γ were determined in full blood samples. The fraction of NK cells expressing CD158a, CD158b, perforin, A, B, and K granzymes was examined in isolated NK cells.We have shown that patients assessed at ALL diagnosis showed significantly lower values of the fraction of NK cells and percentage of NK cells with the granzyme A expression. Additionally, the absolute number of NK cells, the expression of CD158a, CD158b, perforin, and granzyme A were significantly lower in patients who completed intensive chemotherapy. Also, there was a significantly higher fraction of NK cells expressing granzyme K in patients who completed the therapy.Abnormalities of NK cells were found at all stages of the treatment; however, the most pronounced changes were found at the end of intensive chemotherapy.
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Células Asesinas Naturales/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Adolescente , Antineoplásicos/uso terapéutico , Niño , Preescolar , Femenino , Citometría de Flujo , Granzimas/inmunología , Humanos , Lactante , Interferón gamma/inmunología , Células Asesinas Naturales/efectos de los fármacos , Recuento de Linfocitos , Masculino , Perforina/inmunología , Fenotipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Receptores KIR2DL1/inmunología , Receptores KIR2DL3/inmunología , Adulto JovenRESUMEN
In general, detection of peritoneal carcinomatosis (PC) occurs at the late stage when there is no treatment option. In the present study, we designed novel drug delivery systems that are functionalized with anti-CD133 antibodies. The C1, C2 and C3 complexes with cisplatin were introduced into nanotubes, either physically or chemically. The complexes were reacted with anti-CD133 antibody to form the labeled product of A0-o-CX-chem-CD133. Cytotoxicity screening of all the complexes was performed on CHO cells. Data showed that both C2 and C3 Pt-complexes are more cytotoxic than C1. Flow-cytometry analysis showed that nanotubes conjugated to CD133 antibody have the ability to target cells expressing the CD133 antigen which is responsible for the emergence of resistance to chemotherapy and disease recurrence. The shortest survival rate was observed in the control mice group (K3) where no hyperthermic intraperitoneal chemotherapy procedures were used. On the other hand, the longest median survival rate was observed in the group treated with A0-o-C1-chem-CD133. In summary, we designed a novel drug delivery system based on carbon nanotubes loaded with Pt-prodrugs and functionalized with anti-CD133 antibodies. Our data demonstrates the effectiveness of the new drug delivery system and provides a novel therapeutic modality in the treatment of melanoma.