Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
1.
Br J Haematol ; 188(5): 768-773, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31710708

RESUMO

GATA2 deficiency, first described in 2011, is a bone marrow failure disorder resulting in a complex haematological and immunodeficiency syndrome characterised by cytopenias, severe infections, myelodysplasia and leukaemia. The only curative treatment is allogeneic haematopoietic stem cell transplantation (HSCT). Although knowledge on this syndrome has greatly expanded, in clinical practice many challenges remain. In particular, guidelines on optimal donor and stem cell source and conditioning regimens regarding HSCT are lacking. Additionally, genetic analysis of GATA2 is technically cumbersome and could easily result in false-negative results. With this report, we wish to raise awareness of these pitfalls amongst physicians dealing with haematological malignancies and primary immunodeficiencies.


Assuntos
Deficiência de GATA2/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Aloenxertos , Feminino , Deficiência de GATA2/diagnóstico por imagem , Neoplasias Hematológicas/diagnóstico por imagem , Neoplasias Hematológicas/terapia , Humanos , Síndromes de Imunodeficiência/diagnóstico por imagem , Síndromes de Imunodeficiência/terapia , Masculino
2.
Respiration ; 97(5): 472-475, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30928982

RESUMO

GATA2 deficiency is characterized by monocytopenia, deficiency of dendritic cells, and a variable degree of lymphocytopenia affecting B cells and NK cells, leading to an enhanced risk of mycobacterial, viral, and fungal infections. Here we present a patient with a heterozygous intronic GATA2 mutation who acquired a fatal disseminated mycosis due to the black yeast-like fungus Arthrocladium fulminans following an infection with Mycobacterium sherrisii. This case illustrates that in patients with severe uncommon infections, immunodeficiency syndromes must be ruled out.


Assuntos
Antifúngicos/administração & dosagem , Fungos , Deficiência de GATA2 , Síndromes de Imunodeficiência , Infecções Fúngicas Invasivas , Pulmão , Encéfalo/diagnóstico por imagem , Broncoscopia/métodos , Deterioração Clínica , Evolução Fatal , Feminino , Fungos/isolamento & purificação , Fungos/patogenicidade , Deficiência de GATA2/diagnóstico , Deficiência de GATA2/imunologia , Deficiência de GATA2/fisiopatologia , Deficiência de GATA2/terapia , Fator de Transcrição GATA2/genética , Humanos , Síndromes de Imunodeficiência/sangue , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/terapia , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/imunologia , Infecções Fúngicas Invasivas/fisiopatologia , Infecções Fúngicas Invasivas/terapia , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Mutação , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
4.
J Pediatric Infect Dis Soc ; 7(suppl_2): S79-S82, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30590619

RESUMO

Hematopoietic stem cell transplantation (HSCT) has been the standard of care for infants with severe combined immunodeficiency (SCID) for several decades due to the dismal prognosis early in life without immune reconstitution. In recent years, as HSCT conditioning regimens and supportive care have greatly improved, HSCT is gaining in acceptance for more non-SCID primary immunodeficiencies (PIDs) and outside the early childhood period. In addition, potential donor options for non-SCID PIDs are expanding with increasing success for haploidentical donor transplants. In this brief report of a presentation at the PIDS-St. Jude 2018 conference, PIDs for which transplants are increasingly performed outside of early childhood will be discussed.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes de Imunodeficiência/terapia , Criança , Deficiência de GATA2/terapia , Fatores de Troca do Nucleotídeo Guanina/deficiência , Humanos , Lactente , Imunodeficiência Combinada Severa/terapia
5.
Haematologica ; 103(8): 1278-1287, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29724903

RESUMO

Heterozygous germline GATA2 mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.


Assuntos
Deficiência de GATA2/epidemiologia , Mutação em Linhagem Germinativa , Adulto Jovem , Adolescente , Adulto , Bélgica , Criança , Pré-Escolar , França , Deficiência de GATA2/complicações , Deficiência de GATA2/genética , Deficiência de GATA2/terapia , Neoplasias Hematológicas/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Recém-Nascido , Infecções/etiologia , Pessoa de Meia-Idade , Mortalidade , Prognóstico , Inquéritos e Questionários
6.
Biol Blood Marrow Transplant ; 24(6): 1250-1259, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29412158

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. The intensity of conditioning required to achieve reliable engraftment and prevent relapse remains unclear. Here, we describe the results of a prospective study of HSCT in 22 patients with GATA2 deficiency using a busulfan-based conditioning regimen. The study included 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients. MRD and URD recipients received 4 days of busulfan and 4 days of fludarabine. HRD recipients received low-dose cyclophosphamide for 2 days, fludarabine for 5 days, 2 to 3 days of busulfan depending on cytogenetics, and 200 cGy total body irradiation. MRD and URD recipients received tacrolimus and short-course methotrexate for graft-versus-host disease (GVHD) prophylaxis. HRD recipients received high-dose post-transplant cyclophosphamide (PTCy) followed by tacrolimus and mycophenolate mofetil. At a median follow-up of 24 months (range, 9 to 50), 19 of 22 patients were alive with reversal of the disease phenotype and correction of the myelodysplastic syndrome, including eradication of cytogenetic abnormalities. Three patients died: 1 from refractory acute myelogenous leukemia, 1 from GVHD, and 1 from sepsis. There was a 26% incidence of grades III to IV acute GVHD in the MRD and URD groups and no grades III to IV acute GVHD in the HRD cohort. Similarly, there was a 46% incidence of chronic GVHD in the MRD and URD cohorts, whereas only 28% of HRD recipients developed chronic GVHD. Despite excellent overall disease-free survival (86%), GVHD remains a limitation using standard prophylaxis for GVHD. We are currently extending the use of PTCy to the MRD and URD cohorts to reduce GVHD.


Assuntos
Bussulfano/uso terapêutico , Deficiência de GATA2/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Deficiência de GATA2/mortalidade , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doadores de Tecidos , Transplante Homólogo , Adulto Jovem
8.
J Pediatr Hematol Oncol ; 40(6): e383-e388, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29189513

RESUMO

Emberger syndrome with underlying guanine-adenine-thymine-adenine 2 (GATA2) mutation is a rare disorder and very few successful nonmyeloablative allogeneic hematopoietic stem cell transplants (HSCTs) have been reported. We report a case of Emberger syndrome with GATA2 mutation in a 9-year-old girl who presented with congenital sensorineural deafness, warts, lymphedema, and Myelodysplastic syndrome. Her sister had died of a similar illness. She underwent a nonmyeloablative matched related donor peripheral blood HSCT with rabbit antithymoglobulin (5 mg/kg), fludarabine (160 mg/m), cyclophophamide (29 mg/kg), and total body irradiation (2 Gray). Graft versus host disease prophylaxis consisted of tacrolimus and mycophenolate moefetil. She had neutrophil engraftment on day+15 and fully donor chimerism by day+30. She developed limited chronic skin graft versus host disease on tapering off immunosuppression. She is disease free on day+475. The review of literature showed a total of 28 patients with GATA2 mutation have undergone HSCT mostly nonmyeloablative and overall survival is 75%. Nonmyeloablatove HSCT is feasible and safe for the patients with GATA2 mutation.


Assuntos
Deficiência de GATA2/terapia , Fator de Transcrição GATA2/genética , Mutação , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Aloenxertos , Soro Antilinfocitário/administração & dosagem , Criança , Ciclofosfamida/administração & dosagem , Feminino , Deficiência de GATA2/genética , Deficiência de GATA2/patologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Ácido Micofenólico/administração & dosagem , Dermatopatias/genética , Dermatopatias/prevenção & controle , Tacrolimo/administração & dosagem , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Irradiação Corporal Total
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...