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1.
Artigo em Inglês | MEDLINE | ID: mdl-31844137

RESUMO

In the absence of an HLA-matched donor, the best treatment for acquired aplastic anemia patients refractory to immunosuppression is unclear. We collected and analyzed data from all acquired aplastic anemia patients who underwent a haploidentical transplantation with posttransplant cyclophosphamide in Europe from 2011 to 2017 (n = 33). The cumulative incidence of neutrophil engraftment was 67% (CI95%: 51-83%) at D +28 and was unaffected by age group, stem cell source, ATG use, or Baltimore conditioning regimen. The cumulative incidence of grades II-III acute GvHD was 23% at D +100, and limited chronic GvHD was 10% (0-20) at 2 years, without cases of grade IV acute or extensive chronic GvHD. Two-year overall survival was 78% (64-93), and 2-year graft-versus-host disease-free survival was 63% (46-81). In univariate analysis, the 2-year OS was higher among patients who received the Baltimore conditioning regimen (93% (81-100) versus 64% (41-87), p = 0.03), whereas age group, stem cell source, and ATG use had no effect. Our results using unmanipulated haploidentical transplantation and posttransplant cyclophosphamide for treating refractory AA patients are encouraging, but warrant confirmation in a prospective study with a larger number of patients and longer follow-up.

2.
Front Pediatr ; 7: 232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275905

RESUMO

Background and aims: Primary immunodeficiencies (PID) are characterized by recurrent infections and increased risk of malignancies because of the reduced immunological surveillance against cancer cells and oncogenic viruses. Methods: We report the incidence of tumors among 690 patients with PID, diagnosed from 1990 until 2017 in Brescia. Results: Out of 690 patients, 25 patients (3.6%) developed 33 tumors. Of the 25 affected patients, 8 patients suffered from common variable immunodeficiency (CVID), 5 from combined immunodeficiency (CID), 3 from Ataxia-telangectasia (AT), 2 from Hermanksy-Pudlak type 2 (HSP2), 2 from gammaglobulinemia X-linked (XLA), 2 from Wiskott-Aldrich syndrome (WAS), 2 from Hyper IgE syndrome (HIES), 1 from severe combined immunodeficiency (SCID). The age at diagnosis ranged from 1 to 52 years, with a median age of 19.6 years. The time between the diagnosis of PID and onset of tumor was short, often <1 year between diagnosis and the appearance of cancer in the case of CID. Moreover, in two cases of CID, the diagnosis of cancer was made before the diagnosis of PID, so cancer was the onset clinical manifestation. Hematological malignancies were prevalent (22/33, 66.7%) with a minority of solid tumors (11/33, 33.33%). In particular Non-Hodgkin lymphomas were the most frequent (16/33, 48.48%). In total 13 patients survived (52%) and tumor was the main cause of death (7 cases). Two patients underwent BMT once the disease was in remission. Conclusions: Therefore, the correct management of tumors that arise in patients with primitive immunodeficiency still represents a challenge in the pediatric field. For this reason now it is mandatory to collect in a unique international registry the cases of malignancies in PID that could lead to a better understanding of the etiopathogenesis and of the biological and clinical characteristics of these tumors, with the aim of defining adequate preventive measures and guaranteeing an early diagnosis which also creating a shared and specific therapeutic strategy, with the prospect of obtaining a better prognosis for these patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31135716

RESUMO

Ewing sarcoma (ES) is one of the most common pediatric solid tumors with aggressive behavior and unfavorable survival. In this study, we evaluated the diagnostic accuracy of baseline and restaging fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scans and their possible prognostic role in pediatric ES. We evaluated 17 patients who underwent a total of 27 18F-FDG-PET/CT scans (10 for staging and 17 for restaging). The PET images were analyzed visually and semiquantitatively by measuring SUVmean, SUVmax, SUVlbm, SUVbsa, MTV, and TLG. Moreover, PET/CT results were compared with other conventional imaging (CI) results. Among 10 baseline PET/CT scan results, 9 were positive and 1 not valuable by interference; baseline PET/CT and CI were concordant in 7 cases and discordant in 2, with pulmonary micrometastases not detected by PET/CT. Among 17 restaging PET/CT scan results, 9 were positive and 8 negative; CI and restaging PET/CT were concordant in 9 cases and discordant in 8. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of restaging 18F-FDG-PET/CT were 73%, 83%, 89%, 62.5%, and 76%, respectively. After a median follow-up of 20 months, relapse/progression occurred in 8 patients and death in 5. A positive 18F-FDG-PET/CT at restaging was significantly associated with shorter overall survival compared with unremarkable PET/CT at the same timepoint, but not with progression-free survival. Instead, metabolic PET/CT features were not correlated with outcome. 18F-FDG-PET/CT showed a good diagnostic performance in pediatric ES; except for pulmonary micrometastases, PET/CT was better than CI at restaging. Only restaging PET/CT result was significantly correlated with overall survival.

6.
J Allergy Clin Immunol Pract ; 7(5): 1568-1577, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30716504

RESUMO

BACKGROUND: In the warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, variable phenotypic expression may delay diagnosis. Panleukopenia, malignancy, and chronic lung disease all affect morbidity and mortality risks. Routinely used treatments include immunoglobulins, granulocyte-colony stimulating factor (G-CSF), and antibiotics; recent trials with a target C-X-C chemokine receptor type 4 (CXCR4) antagonist show promising results. OBJECTIVE: We sought to characterize the largest cohort of patients with WHIM and evaluate their diagnostic and therapeutic management. METHODS: Data were collected from an international cohort of 18 patients with CXCR4 mutations. RESULTS: The clinical features manifested at 2.2 ± 2.6 years of age, whereas the disease diagnosis was delayed until 12.5 ± 10.4 years of age. Patients with WHIM commonly presented with a severe bacterial infection (78%). Pneumonia recurrence was observed in 61% of patients and was complicated with bronchiectasis in 27%. Skin warts were observed in 61% of patients at a mean age of 11 years, whereas human papilloma virus (HPV)-related malignancies manifested in 16% of patients. All the patients had severe neutropenia (195 ± 102 cells/mm3 at onset), whereas lymphopenia and hypogammaglobulinemia were detected in 88% and 58% of patients, respectively. Approximately 50% of patients received antibiotic prophylaxis, whereas G-CSF and immunoglobulin treatments were used in 72% and 55% of patients, respectively. CONCLUSIONS: The WHIM syndrome onsets early in life and should be suspected in patients with chronic neutropenia. Patients with WHIM need careful monitoring and timely intervention for complications, mainly lung disease and HPV-related malignancies. We suggest that immunoglobulin therapy should be promptly considered to control the frequency of bacterial infections and prevent chronic lung damage.

8.
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.

9.
Bone Marrow Transplant ; 54(2): 275-283, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29899572

RESUMO

Relapse of acute lymphoblastic leukemia (ALL) may occur in extramedullary sites, mainly central nervous system (CNS) and testis. Optimal post-remissional treatment for isolated extramedullary relapse (IEMR) is still controversial. We collected data of children treated with hematopoietic stem cell transplantation (HSCT) for ALL IEMR from 1990 to 2015 in Italy. Among 281 patients, 167 had a relapse confined to CNS, 73 to testis, 14 to mediastinum, and 27 to other organs. Ninety-seven patients underwent autologous HSCT, 79 received allogeneic HSCT from a matched family donor, 75 from a matched unrelated donor, and 30 from an HLA-haploidentical donor. The 10-year overall survival was 56% and was not influenced by gender, ALL blast immune-phenotype, age, site of relapse, duration of first remission, and type of HSCT. In multivariable analysis, the only prognostic factors were disease status at HSCT and year of transplantation. Patients transplanted in third or subsequent complete remission (CR) had a risk of death 2.3 times greater than those in CR2. Children treated after 2000 had half the risk of death than those treated before that year. Our results suggest that both autologous and allogeneic HSCT may be considered for the treatment of pediatric ALL IEMR after the achievement of CR2.

10.
Biol Blood Marrow Transplant ; 24(6): 1223-1231, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29410181

RESUMO

We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34+ cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft.


Assuntos
Linfo-Histiocitose Hemofagocítica/terapia , Adolescente , Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Histocompatibilidade , Humanos , Lactente , Itália , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Recidiva , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
11.
Clin Immunol ; 193: 118-120, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29355610

RESUMO

We describe the case of a child affected by severe combined immunodeficiency (SCID) with adenosine deaminase (ADA) deficiency showing a maternal T-cell engraftment, a finding that has never been reported before. The presence of engrafted maternal T cells was misleading. Although ADA enzymatic levels were suggestive of ADA-SCID, the child did not present the classical signs of ADA deficiency; therefore, the initial diagnosis was of a conventional SCID. However, ADA toxic metabolites and molecular characterization confirmed this diagnosis. Polyethylene glycol-modified bovine (PEG) ADA therapy progressively decreased the number of maternal engrafted T cells. The child was grafted with full bone marrow from a matched unrelated donor, after a reduced conditioning regimen, and the result was the complete immunological reconstitution.


Assuntos
Adenosina Desaminase/deficiência , Adenosina Desaminase/metabolismo , Agamaglobulinemia/diagnóstico , Transplante de Medula Óssea , Quimerismo , Troca Materno-Fetal/imunologia , Imunodeficiência Combinada Severa/diagnóstico , Linfócitos T/fisiologia , Adenosina Desaminase/genética , Agamaglobulinemia/genética , Agamaglobulinemia/terapia , Diagnóstico Diferencial , Erros de Diagnóstico/prevenção & controle , Feminino , Humanos , Lactente , Mães , Gravidez , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/terapia , Resultado do Tratamento
12.
Clin Immunol ; 188: 12-19, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29223406

RESUMO

Chronic Granulomatous Disease (CGD) is caused by the failure of the phagocytes to kill pathogens. We carried out a retrospective analysis of cellular, molecular and clinical features of 14 young patients (mean age at the onset of symptoms and diagnosis: 10 and 25months, respectively), 7 with autosomal recessive and 7 X-linked form, referred to the Children's Hospital of Brescia between 1999 and 2016. Two new mutations were found, one localized in the CYBB and one in the NCF1 genes. Twelve patients were followed in our institution; the average length of their follow-up after diagnosis was 66months in X-linked patients and 126months in autosomal recessive inheritance. The overall survival was 67%, 40% in X-linked and 86% in autosomal recessive form. Eight patients were treated with HSCT. We did not find a clear correlation between the clinical symptoms and the type of mutation, but the fine characterization of the patients was mandatory for therapeutic option, genetic counseling and prenatal diagnosis.


Assuntos
Doença Granulomatosa Crônica/genética , Mutação , NADPH Oxidase 2/genética , NADPH Oxidases/genética , Adolescente , Infecções Bacterianas/diagnóstico , Pré-Escolar , Feminino , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/terapia , Humanos , Lactente , Padrões de Herança , Estimativa de Kaplan-Meier , Linfadenite/diagnóstico , Masculino , Pneumonia/diagnóstico , Estudos Retrospectivos
13.
J Vasc Access ; 19(2): 131-136, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29099537

RESUMO

INTRODUCTION: The aim of our study was to present our experience with the use of peripherally inserted central catheters (PICCs) in pediatric patients receiving autologous or allogenic blood stem-cell transplantation. The insertion of the device in older children does not require general anesthesia and does not require a surgical procedure. METHODS: From January 2014 to January 2017, 13 PICCs were inserted as a central venous device in 11 pediatric patients submitted to 14 autologous or allogeneic stem-cell transplantation, at the Bone Marrow Transplant Unit of the Children's Hospital of Brescia. The mean age of patients at the time of the procedure was 11.3 years (range 3-18 years). PICCs remained in place for an overall period of 4104 days. All PICCs were positioned by the same specifically trained physician and utilized by nurses of our stem-cell transplant unit. RESULTS: No insertion-related complications were observed. Late complications were catheter ruptures and line occlusions (1.2 per 1000 PICC days). No rupture or occlusion required removal of the device. No catheter-related venous thrombosis, catheter-related bloodstream infection (CRBSI), accidental removal or permanent lumen occlusion were observed. Indications for catheter removal were completion of therapy (8 patients) and death (2 patients). Three PICCs are currently being used for blood sampling in follow-up patients after transplantation. CONCLUSIONS: Our data suggest that PICCs are a safe and effective alternative to conventional central venous catheters even in pediatric patients with high risk of infectious and hemorrhagic complications such as patients receiving stem-cell transplantation.


Assuntos
Cateterismo Venoso Central/instrumentação , Cateterismo Periférico/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Fatores Etários , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Criança , Pré-Escolar , Desenho de Equipamento , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Fatores de Risco , Fatores de Tempo , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento
14.
J Clin Immunol ; 37(7): 701-706, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28815344

RESUMO

PURPOSE: Complete signal transducer and activator of transcription 1 (STAT1) deficiency is a rare autosomal recessive condition characterized by impairment of intracellular signaling from both type I and type II interferons (IFN). Affected patients are prone to early severe mycobacterial and viral infections, which usually result in death before 18 months of age. We previously reported a patient affected by complete STAT1 deficiency who underwent hematopoietic stem cell transplantation (HSCT). Here, we describe the transplantation procedures and long-term outcomes. METHODS: The patient, who had suffered multiple life-threatening mycobacterial and viral infections in the first years of life, underwent HSCT at 4 years of age from a partially matched (HLA compatibility 8/10) unrelated donor after a myeloablative conditioning regimen consisting of busulfan, cyclophosphamide, and anti-thymocyte globulin. RESULTS: Hematological reconstitution was detected at d+15, with full donor engraftment demonstrated by molecular analysis of leukocytes. Several complications occurred in the post-transplantation phase, including acute graft versus host disease, posterior reversible encephalopathy, thrombotic thrombocytopenic purpura, bilateral keratoconjunctivitis with complete loss of vision, and chronic lower limb lymphedema. Analysis of STAT1 in CD3+ cells at 90 and 120 days after HSCT by flow cytometry showed normal STAT1 phosphorylation levels in response to IFN-α. CONCLUSIONS: Notably, no severe infections occurred after discharge (day + 90) during a 9-year follow-up, suggesting that normal response to IFNs in hematopoietic cells is sufficient to provide protection in humans.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência/terapia , Fator de Transcrição STAT1/deficiência , Pré-Escolar , Humanos , Masculino , Resultado do Tratamento
15.
Blood ; 129(21): 2928-2938, 2017 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-28331055

RESUMO

Reticular dysgenesis (RD) is a rare congenital disorder defined clinically by the combination of severe combined immunodeficiency (SCID), agranulocytosis, and sensorineural deafness. Mutations in the gene encoding adenylate kinase 2 were identified to cause the disorder. Hematopoietic stem cell transplantation (HSCT) is the only option to cure this otherwise fatal disease. Retrospective data on clinical presentation, genetics, and outcome of HSCT were collected from centers in Europe, Asia, and North America for a total of 32 patients born between 1982 and 2011. Age at presentation was <4 weeks in 30 of 32 patients (94%). Grafts originated from mismatched family donors in 17 patients (55%), from matched family donors in 6 patients (19%), and from unrelated marrow or umbilical cord blood donors in 8 patients (26%). Thirteen patients received secondary or tertiary transplants. After transplantation, 21 of 31 patients were reported alive at a mean follow-up of 7.9 years (range: 0.6-23.6 years). All patients who died beyond 6 months after HSCT had persistent or recurrent agranulocytosis due to failure of donor myeloid engraftment. In the absence of conditioning, HSCT was ineffective to overcome agranulocytosis, and inclusion of myeloablative components in the conditioning regimens was required to achieve stable lymphomyeloid engraftment. In comparison with other SCID entities, considerable differences were noted regarding age at presentation, onset, and type of infectious complications, as well as the requirement of conditioning prior to HSCT. Although long-term survival is possible in the presence of mixed chimerism, high-level donor myeloid engraftment should be targeted to avoid posttransplant neutropenia.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas , Leucopenia/mortalidade , Leucopenia/terapia , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/terapia , Condicionamento Pré-Transplante , Doadores não Relacionados , Adenilil Ciclases/genética , Adenilil Ciclases/metabolismo , Adolescente , Adulto , Idade de Início , Aloenxertos , Criança , Intervalo Livre de Doença , Feminino , Humanos , Leucopenia/enzimologia , Leucopenia/genética , Masculino , Imunodeficiência Combinada Severa/enzimologia , Imunodeficiência Combinada Severa/genética , Taxa de Sobrevida
16.
Eur J Immunol ; 47(2): 327-344, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27859047

RESUMO

Switched and IgM memory B cells execute different and noninterchangeable functions. We studied memory B cells in children of different ages, in peripheral blood and spleen and compared them with those of children born asplenic or unable to build germinal centers. We show that, whereas switched memory B cells are mostly generated in the germinal centers at all ages, IgM memory B cells can be distinct in three types with different developmental history. Innate IgM memory B cells, the largest pool in infants, are generated in the spleen by a germinal center-independent mechanism. With age, if the spleen is present and germinal centers are functional, innate IgM memory B cells are remodelled and accumulate somatic mutations. The third type of IgM memory B cell is a by-product of the germinal center reaction. Our data suggest that the B-cell memory developmental program is implemented during the first 5-6 years of life.


Assuntos
Envelhecimento/imunologia , Linfócitos B/imunologia , Centro Germinativo/imunologia , Memória Imunológica , Baço/imunologia , Adolescente , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Imunidade Inata , Switching de Imunoglobulina , Imunoglobulina M/metabolismo , Lactente , Masculino , Especificidade de Órgãos , Linfócitos T/imunologia
17.
J Pediatr Hematol Oncol ; 38(7): 559-62, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27571124

RESUMO

The aim of this study was to assess the efficacy of a solution composed by verbascoside, polyvinylpyrrolidone, and sodium hyaluronate (Mucosyte) in the treatment of chemotherapy-induced oral mucositi (OM). Patients between 5 and 18 years receiving chemotherapy for acute lymphoblastic leukemia and with OM grade 1 or 2 were randomized in group A (treated with Mucosyte, 3 mouthwashes/d per 8 d) and group B (treated with placebo, ie, an inert water-based solution, 3 mouthwashes/d per 8 d). The OM scoring was performed at day 1 (diagnosis of OM-T0), after 3 days of treatment (T1), and at day 8 (T2). Pain was evaluated through the visual analog scale with the same timing of OM measurement. A total of 56 patients were included (28 patients per group). Group A experienced a statistically significant decline of OM at T2 (P=0.0038); a statistically significant difference in pain reduction between 2 groups both at T1 and at T2 (P<0.005) was observed. The use of Mucosyte mouthwashes in children with chemotherapy-induced OM may be recommended as supportive therapy.


Assuntos
Antineoplásicos/efeitos adversos , Glucosídeos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Fenóis/administração & dosagem , Povidona/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estomatite/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Método Duplo-Cego , Humanos , Soluções , Estomatite/induzido quimicamente
18.
Blood ; 127(26): 3382-6, 2016 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-27207797

RESUMO

Hermansky-Pudlak syndrome type 2 (HPS2) is a primary immunodeficiency due to adaptor protein-3 (AP-3) complex deficiency. HPS2 patients present neutropenia, partial albinism, and impaired lysosomal vesicles formation in hematopoietic cells. Given the role of dendritic cells (DCs) in the immune response, we studied monocyte-derived DCs (moDCs) and plasmacytoid DCs (pDCs) in two HPS2 siblings. Mature HPS2 moDCs showed impaired expression of CD83 and DC-lysosome-associated membrane protein (LAMP), low levels of MIP1-ß/CCL4, MIG/CXCL9, and severe defect of interleukin-12 (IL-12) secretion. DCs in lymph-node biopsies from the same patients showed a diffuse cytoplasm reactivity in a large fraction of DC-LAMP(+) cells, instead of the classical dot-like stain. In addition, analysis of pDC-related functions of blood-circulating mononuclear cells revealed reduced interferon-α secretion in response to herpes simplex virus-1 (HSV-1), whereas granzyme-B induction upon IL-3/IL-10 stimulation was normal. Finally, T-cell costimulatory activity, as measured by mixed lymphocyte reaction assay, was lower in patients, suggesting that function and maturation of DCs is abnormal in patients with HPS2.


Assuntos
Complexo 3 de Proteínas Adaptadoras/deficiência , Células Dendríticas/imunologia , Regulação da Expressão Gênica/imunologia , Síndrome de Hermanski-Pudlak/imunologia , Monócitos/imunologia , Complexo 3 de Proteínas Adaptadoras/imunologia , Antígenos CD/genética , Antígenos CD/imunologia , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/imunologia , Citocinas/genética , Citocinas/imunologia , Células Dendríticas/patologia , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Granzimas/genética , Granzimas/imunologia , Síndrome de Hermanski-Pudlak/genética , Síndrome de Hermanski-Pudlak/patologia , Herpesvirus Humano 1/imunologia , Humanos , Imunoglobulinas/genética , Imunoglobulinas/imunologia , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Monócitos/patologia , Linfócitos T/imunologia , Linfócitos T/patologia
20.
J Clin Immunol ; 35(7): 624-37, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26376800

RESUMO

PURPOSE: We carried out a retrospective analysis of 27 patients with Adenosine Deaminase (ADA) deficiency diagnosed in a single center from 1997 to the 2013, for evaluating whether data regarding types of disease-inducing mutations, biochemical and immunological features as well as clinical outcomes of patients treated with enzyme replacement or transplantation, were comparable to those obtained in multicenter studies. METHODS: The ADA deficiency diagnosis was performed with biochemical, immunological and molecular techniques. Ten patients treated with hematopoietic stem cell transplantation and three in treatment with enzyme replacement were followed up in our center. RESULTS: Twenty-four different mutations were identified and five were not previously reported. Identical mutations were found among patients from the same Romani ethnic group or from the same geographical region. A more rapid recovery was observed in enzyme replacement treated patients in comparison with those transplanted that, however, showed a continuous and long-lasting improvement both in terms of immune and metabolic recovery. CONCLUSION: The data obtained in our single center are comparable with those that have been reported in multicenter surveys.


Assuntos
Adenosina Desaminase/deficiência , Adenosina Desaminase/metabolismo , Agamaglobulinemia/diagnóstico , Terapia de Reposição de Enzimas , Terapia Genética , Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa/diagnóstico , Adenosina Desaminase/genética , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/terapia , Pré-Escolar , Consanguinidade , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Lactente , Itália , Masculino , Mutação/genética , Estudos Retrospectivos , Roma , Imunodeficiência Combinada Severa/epidemiologia , Imunodeficiência Combinada Severa/terapia , Resultado do Tratamento
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