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2.
Cancer Rep (Hoboken) ; 6(12): e1912, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37867416

RESUMO

BACKGROUND: The mitogen-activated protein kinase (MAPK)/ERK signaling cascade and the phosphoinosytol-3 phosphate/Akt (PI3K/Akt) pathways are involved in proliferation and differentiation of hematopoietic cells. The frequency of PI3K/Akt and MAPK pathway activation in adult acute lymphoblastic leukemia (ALL) still need to be elucidated. AIMS: To assess the activity and prognostic implications of MAPK/ERK and PI3K/Akt pathways in adult (ALL). METHODS: We examined 28 precursor-B-cell ALL and 6 T-cell primary ALL samples. Flow cytometry was employed to analyze the expression levels of phosphorylated ERK and phosphorylated Akt. RESULTS: Ten out of 15 (67%) ALL fresh samples (7 B-cell, 3 T-cell) showed constitutive p-ERK expression. The p-ERK mean fluorescent index ratio (MFI (R)) showed a tendency to be higher in ALL than in normal T lymphocytes (1.26 [0.74-3.10] vs. 1.08 [1.02-1.21], respectively [p = .069]) and was significantly lower than in leukemic cell lines (median MFI (R) 3.83 [3.71-5.97] [p < .001]). Expression of p-Akt was found in 35% (12/34) (10 B-cell, 2 T-cell). The median MFI (R) expression for p-Akt in primary blast cell was 1.13 (0.48-9.90) compared to 1.01 (1.00-1.20) in normal T lymphocytes (p = ns) and lower than in leukemic cell lines (median MFI (R) 2.10 [1.77-3.40] [p = .037]). Moreover, expression of p-ERK was negatively associated with the expression of CD34 (1.22 [0.74-1.33] vs. 1.52 [1.15-3.10] for CD34(+) and CD34(-) group, respectively, p = .009). CONCLUSION: Our findings suggest that both MAPK/ERK and PI3K/Akt are constitutively activated in adult ALL, indicating a targeted therapy potential for ALL by using inhibitors of these pathways.


Assuntos
Proteínas Quinases Ativadas por Mitógeno , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/fisiologia
3.
Transpl Infect Dis ; 25(4): e14098, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37428874

RESUMO

INTRODUCTION: Measles, mumps, rubella, and even poliomyelitis outbreaks have recently perplexed infectious disease clinicians and epidemiologists globally due to the decline in vaccination coverage rates in children and adults. Measles and yellow fever (YF) have represented an increasing burden on the Brazilian public health system in recent decades. Both diseases are preventable by live-attenuated viral vaccines (LAVV), which have restricted use in hematopoietic cell transplant (HCT) recipients. METHODS: Autologous and allogeneic HCT recipients returning for regular appointments at the outpatient clinic were invited to participate in the study. Patients transplanted for at least 2 years and with a printed copy of the vaccination record were included. RESULTS: We assessed the vaccination records of 273 HCT recipients after the second year of HCT (193 allogeneic and 80 autologous) and observed lower compliance with the YF vaccine (58 patients, 21.2%) than with the measles vaccine (138 patients, 50.5%, p ≤ .0001). This is the largest published series of YF vaccination in HCT recipients so far. No severe adverse events occurred. Although expected, chronic graft-versus-host disease (GVHD) did not affect the compliance with measles (p = .08) or YF vaccination (p = .7). Indeed, more allogeneic recipients received measles vaccine in comparison with autologous patients (p < .0001), suggesting that chronic GVHD was not the main reason for not being vaccinated. Children and allogeneic HCT were more likely to receive measles vaccine. Time elapsed from HCT >5 years favored both measles and YF vaccination. CONCLUSION: A better understanding of the reasons for low compliance with LAVV is necessary to overcome this problem.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sarampo , Vacina contra Febre Amarela , Febre Amarela , Adulto , Criança , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunização Secundária , Sarampo/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Vacinação , Vacinas Virais , Febre Amarela/prevenção & controle , Vacina contra Febre Amarela/administração & dosagem
4.
Hematol Transfus Cell Ther ; 43 Suppl 2: S13-S21, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34794791

RESUMO

Chimeric antigen receptor T (CAR-T) cell therapy is a novel therapeutic modality for acute lymphoblastic leukemia (ALL) with robust outcomes in patients with refractory or relapsed disease. At the same time, CAR-T cell therapy is associated with unique and potentially fatal toxicities, such as cytokine release syndrome (CRS) and neurological toxicities (ICANS). This manuscript aims to provide a consensus of specialists in the fields of Hematology Oncology and Cellular Therapy to make recommendations on the current scenario of the use of CAR-T cells in patients with ALL.

5.
Bone Marrow Transplant ; 56(9): 2241-2247, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33966056

RESUMO

Tuberculosis (TB) is a major infectious complication in hematopoietic stem cell transplant (HSCT) recipients in countries with high TB prevalence. Identifying and treating latent tuberculosis infection (LTBI) helps to prevent TB reactivation after transplantation. Few studies have compared the tuberculin skin test (TST) with interferon Gamma release assays (IGRA) to diagnose LTBI in HSCT candidates. We compared TST and QuantiFeron TB gold in tube (QTF-GIT) and prospectively evaluated the incidence of active tuberculosis in 126 HSCT candidates and 58 HSCT recipients with chronic GVHD followed at the outpatient clinic. TB was diagnosed by culture in Mycobacteria media and by commercial real-time PCR kit. Considering the positivity of any test, the prevalence of LTBI was 8.7% in HSCT candidates (11 out of 126) and 12.5% in HSCT recipients with chronic GVHD (6 out of 48). QTF-GIT indeterminate results were detected in 2.4% of the HSCT candidates. Fair to good agreement (K > 0.50) between tests was observed in both cohorts. Cumulative incidence of TB was 3% in the GVHD cohort. TB was diagnosed in 2 chronic GVHD recipients, both cases confirmed by positive culture and PCR. None of the 11 patients with LTBI diagnosed pre-HSCT who received INH prophylaxis developed TB.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Tuberculose , Estudos de Coortes , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Prospectivos , Teste Tuberculínico , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/etiologia
6.
Eur J Haematol ; 105(4): 426-433, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32525237

RESUMO

OBJECTIVES: The aim of this study was to analyze the outcomes of children with Diamond-Blackfan anemia (DBA) treated in Brazil with hematopoietic cell transplantation (HCT). METHODS: We performed a retrospective analysis of 44 pediatrics patients transplanted between 1990 and 2018. The median age of patients was 5 years, and 57% were male. Twenty-five received their first HCT from an HLA-matched sibling donor (MSD), 12 from a HLA matched unrelated bone marrow donor (MUD 10/10, n = 12) and 7 other HLA mismatched donors (MMD). RESULTS: After a median follow-up of 4 years, estimate 5-year overall survival (OS) for the entire cohort was 70%, 80% for MSD group, 73% for MUD, and 29% for MMD. Thirty-eight out of the 44 evaluable patients engrafted successfully. Primary and secondary graft failure was observed in five and three patients, respectively. Rates of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 25% and 18%, respectively. Nine patients developed chronic GVHD (cGVHD). CONCLUSION: Overall survival rates observed after HLA matched donors transplant for DBA were comparable to those reported from higher-income countries and international registries.


Assuntos
Anemia de Diamond-Blackfan/terapia , Transplante de Células-Tronco Hematopoéticas , Anemia de Diamond-Blackfan/diagnóstico , Anemia de Diamond-Blackfan/epidemiologia , Transplante de Medula Óssea , Brasil/epidemiologia , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/genética , Pesquisas sobre Atenção à Saúde , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Irmãos , Doadores não Relacionados
7.
Transpl Infect Dis ; 22(3): e13258, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32034983

RESUMO

BACKGROUND: Hepatitis A virus (HAV) infection is highly prevalent in developing countries. In countries experiencing a shift from intermediate/high endemicity to low endemicity, the World Health Organization recommends the incorporation of HAV vaccine into the national vaccination calendar for children aged ≥1 year. Since HAV antibodies wane over time, most HSCT revaccination guidelines advise vaccination as optional, following the country recommendation. However, no study has evaluated the serological response to HAV vaccine in allogeneic HSCT recipients. METHODS: We conducted a prospective study in 46 HSCT recipients who received two doses of inactivated HAV vaccine. Blood samples were taken before vaccination to determine HAV prevalence rates, and before and 4-6 weeks after the second dose. Specific anti-HAV antibodies were detected by a competitive commercial enzyme immune assay. RESULTS: Patients received the first dose of vaccine at a median of 332.5 (120-4134) days after HSCT. Median absolute lymphocyte count at vaccination was 1947 (696-12 500)/mm3 . The seroprevalence rate was 93.5% at inclusion. Although safe and well tolerated, the serological response to HAV vaccine in susceptible patients was poor (33%), and no boost effect was observed in seropositive patients. CONCLUSIONS: In areas with intermediate/high seroprevalence of HAV, serology should be recommended prior to referral to vaccination. The mechanisms of antibody interference and how to overcome T-cell function deficiency need to be better understood in transplant populations receiving HAV vaccine. Alternative schedules of HAV vaccination should be evaluated in prospective trials.


Assuntos
Anticorpos Antivirais/sangue , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vacinas contra Hepatite A/imunologia , Hepatite A/prevenção & controle , Imunogenicidade da Vacina , Adolescente , Adulto , Idoso , Países em Desenvolvimento , Feminino , Vacinas contra Hepatite A/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Soroepidemiológicos , Vacinação , Adulto Jovem
8.
Pediatr Transplant ; 23(7): e13552, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31297928

RESUMO

In this study, we report on major MRD or URD BMT outcomes in pediatric patients with SAA in Brazil. This was a retrospective study, which included 106 patients ≤18 years old who received a first BMT for SAA. All patients received bone marrow as graft source from an MRD (n = 69) or a URD (n = 37). Conditioning regimen was non-myeloablative in 73.6% of cases, and GVHD prophylaxis comprised a calcineurin inhibitor plus methotrexate in 89.6% of patients. After a median follow-up of 4.5 years after BMT, 81 patients are alive, with a 4-year OS of 77% and no statistically significant difference between the MRD and URD groups (82% vs. 69%, respectively; P = .08). Grade III-IV aGVHD at 6 months and cGVHD at 2 years were observed in 8% and 14% of cases, respectively, and were not statistically different between the groups. Twenty-five (23%) patients died at a median of 2.9 months after BMT. Our study showed that 4-year OS after BMT was not statistically different between MRD and URD recipients. This study shows that the outcomes of pediatric patients transplanted for SAA with a URD in Brazil are approaching those of MRD transplants. In contrast, OS after MRD BMT was lower than we would expect based on previous reports. The wide range of preparatory regimens used by the study centers highlights the need for standardized protocols for these children. Our findings provide a benchmark for future studies focused on improving BMT outcomes in this setting in Brazil.


Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/métodos , Doadores não Relacionados , Adolescente , Brasil , Criança , Pré-Escolar , Países em Desenvolvimento , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Cooperação Internacional , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Transplante Homólogo , Resultado do Tratamento , Washington
9.
Front Immunol ; 9: 1889, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30245685

RESUMO

Hematopoietic stem cell transplantation (HSCT) is an important therapeutic option for some hematological diseases. However, patients who undergo HSCT acquire a state of immunodeficiency that causes significant mortality. Reconstitution of thymic function is needed to support the immune system. One way to measure thymic function is through T-cell receptor excision circle (TREC) quantification. TRECs are generated by T-cell receptor gene rearrangements during T-cell maturation in the thymus and represent a reliable marker for thymic output. In this study, we aimed to assess aging and malignant hematological diseases as two important factors that may influence thymic output before HSCT. We observed that patients before HSCT presented signal joint TREC (sjTREC) numbers lower than 606.55 copies/µg DNA (low values) compared with healthy individuals, with an odds ratio (OR) of 12.88 [95% confidence interval (CI): 5.26-31.53; p < 0.001]. Our results showed that a group of older individuals (≥50 years old), comprising both healthy individuals and patients, had an OR of 10.07 (95% CI: 2.80-36.20) for low sjTREC values compared with younger individuals (≤24 years old; p < 0.001). Multiple logistic regression analysis confirmed that both older age (≥50 years old) and malignant hematological diseases and their treatments were important and independent risk factors related to thymic function impairment (p < 0.001). The median sjTREC value for patients of all ages was significantly lower than the sjTREC median for the subgroup of older healthy individuals (≥50 years old; p < 0.001). These data suggested that patients before HSCT and healthy individuals exhibited age-dependent thymic impairment, and that prior treatment for hematological diseases may exacerbate aging-related deterioration of natural thymic function. Furthermore, we analyzed these patients 9 months post-HSCT and compared patients who underwent autologous HSCT with those who underwent allogeneic HSCT. Both groups of patients achieved sjTREC copy numbers similar to those of healthy individuals. We did not find a close relationship between impaired thymic function prior to HSCT and worse thymic recovery after HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Linfopoese , Timo/citologia , Timo/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/metabolismo , Adulto Jovem
10.
Biol Blood Marrow Transplant ; 24(4): 799-805, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29288817

RESUMO

Body mass index (BMI) may influence outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). However, the impact of BMI on survival in children undergoing HSCT is not well defined, with conflicting results being reported on this issue. We analyzed 855 patients age 2 to 20 years with diagnosis of acute leukemia who underwent umbilical cord blood transplantation (UCBT) from 1990 to 2015. Patients were classified according to BMI as normal (fifth to 85th percentile), underweight (less than fifth percentile), overweight (85th to 95th percentile), and obese (>95th percentile) using growth charts for age and sex. All patients received single-unit UCBT after a myeloablative conditioning regimen. Diagnosis was acute lymphoblastic leukemia in 68% of the patients. Sixty-one percent of patients (n = 523) were in the normal BMI category, 11% (n = 96) were underweight, 16% (n = 137) overweight, and 12% (n = 99) obese. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was 35% (32% to 38%). According to pretransplantation BMI, aGVHD was 46% (33% to 59%) for underweight, 34% (31% to 42%) for normal, 36% (18% to 38%) for overweight, and 27% (15% to 37%) for obese (P = .04). In multivariate analysis, a BMI less than the fifth percentile was associated with higher incidence of acute grade II to IV GVHD compared with normal-BMI patients (hazard ratio, 1.61; 95% confidence interval, 1.15 to 2.26; P = .006). Our results show that being underweight at the time of transplantation is associated with an increased risk of aGVHD, highlighting the importance of nutritional status before UCBT.


Assuntos
Índice de Massa Corporal , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Leucemia , Estado Nutricional , Doença Aguda , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Leucemia/mortalidade , Leucemia/patologia , Leucemia/fisiopatologia , Leucemia/terapia , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida
11.
Rev Inst Med Trop Sao Paulo ; 59: e69, 2017 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-29116289

RESUMO

Hematopoietic stem cell transplant (HSCT) recipients should be routinely revaccinated after transplantation. We evaluated the difficulties met in the revaccination program and how a prospective and tailored follow-up could help to overcome these obstacles. HSCT recipients (n=122) were prospectively followed up and categorized into Group 1 (n=72), recipients who had already started the revaccination program, and Group 2 (n=50), recipients starting their vaccines. Whenever a difficulty was reported, interventions and subsequent evaluations were performed. Reported problems were related to patient compliance, HSCT center and/or vaccination center. Problems related to patient compliance were less frequent than those related to HSCT center modifications of previous recommendations, or to errors made by the vaccination center. The main gap found was vaccination delays (81.9%). Advisory intervention was needed in 64% and 46% of Group 1 and Group 2, respectively (p=0.05), and was partially successful in around 70% of the cases. Total resolution was achieved in more than 35% in both groups. Improvements are needed in the Brazilian vaccination program for HSCT recipients to assure a complete and updated revaccination schedule. HSCT centers should assign nurses and transplant infectious disease specialist physicians to organize the revaccination schedule and to monitor the program development.


Assuntos
Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Esquemas de Imunização , Imunização Secundária , Adolescente , Adulto , Idoso , Vacinas Bacterianas/administração & dosagem , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Imunização Secundária/estatística & dados numéricos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vacinas Virais/administração & dosagem , Adulto Jovem
12.
Blood Adv ; 1(10): 624-627, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-29296705

RESUMO

Aedes mosquitoes are well adapted in domestic environments and widespread in tropical regions. Since 2015, Brazil has been experiencing a triple epidemic of dengue (DENV), chikungunya (CHKV), and Zika (ZIKV) viruses. The last 2 viruses are likely following the path of DENV, which has been endemic in most parts of the country since the 1980s. Given this triple epidemic, we proposed a prospective and collaborative study to assess the prevalence, morbidity, and mortality of DENV, CHKV, and ZIKV infections in hematopoietic stem cell transplant (HSCT) recipients and oncohematological patients. A case definition strategy (fever and rash) was used to prompt diagnostic investigation of DENV, ZIKV, and CHKV, which was accomplished by real-time polymerase chain reaction with plasma and urine samples. Clinical follow-up was performed 7 and 30 days after symptom onset. We report here the first cases of ZIKV and CHKV infections diagnosed in this ongoing study. From February to May 2016, 9 of the 26 patients (34.6%) fulfilling case definition criteria were diagnosed with DENV (3 cases), ZIKV (4 cases), or CHKV (2 cases) infections. Prolonged viremia and viruria were observed in dengue and Zika fever cases, respectively. Thrombocytopenia was the most frequent complication. Delayed engraftment was noted in 1 patient who acquired ZIKV 25 days before HSCT. All patients survived without sequelae. With the geographic expansion of arboviruses, donor and recipient screening may become mandatory. Patients living in areas where these viruses are not endemic are also at risk, since these viruses can be transmitted by blood as well as organ or tissue transplantation.

13.
Ann Hematol ; 96(1): 65-72, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27815724

RESUMO

Relatively little is known about the outcomes of multiple myeloma in Latin America, a world region where incorporation of novel agents is generally slow. In the current retrospective-prospective study, we aimed to describe the patterns of care and treatment results in five Latin American countries. Between April 2007 and October 2009, patients who had been diagnosed from January 2005 to December 2007 were registered at 23 institutions from Argentina, Brazil, Chile, Mexico, and Peru. We divided patients into two cohorts, according to transplantation eligibility, and analyzed them with regard to first-line treatment and overall survival (OS). We analyzed a total of 852 patients, 46.9 % of whom were female. The median follow-up was 62 months. Among transplantation-ineligible patients (N = 461), the mean age was 67.4 years, approximately one third of patients received a thalidomide-based treatment in the first line, and the median OS was 43.0 months. Transplantation-eligible patients (N = 391) had a mean age of 54.7 years and a median OS of 73.6 months. Autologous transplantation was performed in 58.6 % of the patients for whom this procedure was initially planned and in only 26.9 % of the overall patients. Our long-term results reflect the contemporary literature for patients with multiple myeloma treated with autologous transplantation and thalidomide-based regimens in clinical trials and observational studies. However, further efforts are needed to approve and incorporate novel agents in Latin American countries, as well as to increase access to transplantation, in order to achieve the expected improvements in patient outcomes.


Assuntos
Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , América Latina/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos
14.
Braz. j. otorhinolaryngol. (Impr.) ; 81(2): 141-147, Mar-Apr/2015. tab
Artigo em Inglês | LILACS | ID: lil-745801

RESUMO

INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation receive high doses of chemotherapy and radiotherapy, which cause severe immunosuppression. OBJECTIVE: To report an oral disease management protocol before and after hematopoietic stem cell transplantation. METHODS: A prospective study was carried out with 65 patients aged > 18 years, with hematological diseases, who were allocated into two groups: A (allogeneic transplant, 34 patients); B (autologous transplant, 31 patients). A total of three dental status assessments were performed: in the pre-transplantation period (moment 1), one week after stem cell infusion (moment 2), and 100 days after transplantation (moment 3). In each moment, oral changes were assigned scores and classified as mild, moderate, and severe risks. RESULTS: The most frequent pathological conditions were gingivitis, pericoronitis in the third molar region, and ulcers at the third moment assessments. However, at moments 2 and 3, the most common disease was mucositis associated with toxicity from the drugs used in the immunosuppression. CONCLUSION: Mucositis accounted for the increased score and potential risk of clinical complications. Gingivitis, ulcers, and pericoronitis were other changes identified as potential risk factors for clinical complications. .


INTRODUÇÃO: Pacientes submetidos a transplante de células hematopoiéticas recebem altas doses de quimioterapia e radioterapia que podem causar imunossupressão e doenças orais graves. OBJETIVO: Apresentar um protocolo de avaliação de doenças orais antes e após transplante de células hematopoiéticas. MÉTODO: Estudo clínico prospectivo de 65 pacientes com idade acima de 18 anos, com doenças hematológicas submetidas a transplante de células hematopoiéticas, divididos em dois grupos: A (transplante alogênico, 34 pacientes) e B (transplante autólogo). Foram realizadas três avaliações odontológicas: período antes do transplante (momento 1), uma semana (momento 2) e 100 dias após o transplante (momento 3). Em cada momento as alterações orais foram pontuadas e classificadas como leve, moderada e grave. RESULTADOS: As alterações orais mais frequentes foram: gengivite, pericoronite do terceiro molar e úlceras. Entretanto nos momentos dois e três a principal doença foi a mucosite associada a toxicidades das drogas usadas na imunossupressão. CONCLUSÃO: Mucosite foi principal alteração, com a pontuação mais alta e com maior risco de complicações. Gengivites, úlceras e pericoronites foram outras alterações com risco menor de complicações. .


Assuntos
Humanos , Masculino , Adolescente , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças da Boca/etiologia , Terapia de Imunossupressão/efeitos adversos , Estudos Prospectivos , Fatores de Risco
15.
Biol Blood Marrow Transplant ; 21(7): 1223-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25792371

RESUMO

Dendritic cells (DCs) are antigen-presenting cells that drive immune responses and tolerance and are divided in different subsets: myeloid DCs (mDCs: lineage-; HLA-DR+, 11c+), plasmacytoid dendritic cells (pDCs: HLA-DR+, CD123+), and monocyte-derived DCs (moDC: lineage-, 11c+, 16+). After hematopoietic stem cell transplantation (HSCT), low DC counts in the recipients' peripheral blood (PB) have been associated with worse outcomes, but the relevance of DC graft content remains unclear, and there are few data in the setting of unrelated donor HSCT. We evaluated the DC graft content and monitored DC recovery in PB from 111 HSCT recipients (median age, 17 years; range 1 to 74), who received bone marrow (46%), umbilical cord blood (32%), or PB (22%) from unrelated (81%) or related donors (19%). In 86 patients with sustained allogeneic recovery, patients with higher counts of all DC subsets (pDC, mDC, and moDC) 3 weeks after engraftment had lower incidence of nonrelapse mortality (NMR) and acute graft-versus-host disease (aGVHD) and better survival. pDC counts were associated with more striking results: patients with higher pDC counts had much lower incidences of NRM (3% versus 47%, P < .0001), lower incidence of aGVHD (24% versus 67%, P < .0001), and better overall survival (92% versus 45%, P < .0001). In contrast, higher pDC counts in the graft was associated with an increased risk of aGVHD (55% versus 26%, P = .02). Our results indicate that DC counts are closely correlated with HSCT outcomes and warrant further prospective evaluation and possible early therapeutic interventions to ameliorate severe aGVHD and decrease mortality.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Células Dendríticas/patologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante , Doença Aguda , Adolescente , Adulto , Idoso , Contagem de Células , Linhagem da Célula/imunologia , Criança , Pré-Escolar , Células Dendríticas/classificação , Células Dendríticas/imunologia , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/uso terapêutico , Lactente , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Irmãos , Análise de Sobrevida , Transplante Homólogo , Doadores não Relacionados
16.
Eur J Haematol ; 95(5): 421-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25645430

RESUMO

OBJECTIVES: The objective of this study was to compare the major transplant outcomes between patients receiving hematopoietic stem cell transplantation (HSCT) from bone marrow (BM) or peripheral blood stem cells (PBSC). METHODS: All consecutive HSCT patients using BM or PBSC from an HLA-matched related donors for haematological malignancies after high intensity conditioning at seven Brazilian transplant centres between January 2008 and December 2009 were retrospectively evaluated. RESULTS: In the study period, 334 patients were treated in the centres and included in the evaluation. The cumulative incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD) at one year was 36.7% and 9.7% for BM recipients and 34.4% and 15.1% for PBSC recipients, respectively (not statistically different). The cumulative incidence of chronic GVHD at three years was 53.7% and 79.8% (HR 1.93; 95% CI 1.38-2.69, P < 0.001) for BM and PBSC, respectively. Median overall survival was 2.85 and 2.39 years for BM and PBSC recipients, respectively (HR 1.19; 95% CI, 0.84-1.68, P = 0.34). CONCLUSIONS: Our results confirm previous findings of increased chronic GVHD incidence in patients receiving PBSC when compared to patients receiving BM as the graft source in HSCT. Acute GVHD incidence, progression-free survival and overall survival were not different between the groups.


Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico , Doadores de Tecidos , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
17.
Braz J Otorhinolaryngol ; 81(2): 141-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25458262

RESUMO

INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation receive high doses of chemotherapy and radiotherapy, which cause severe immunosuppression. OBJECTIVE: To report an oral disease management protocol before and after hematopoietic stem cell transplantation. METHODS: A prospective study was carried out with 65 patients aged>18 years, with hematological diseases, who were allocated into two groups: A (allogeneic transplant, 34 patients); B (autologous transplant, 31 patients). A total of three dental status assessments were performed: in the pre-transplantation period (moment 1), one week after stem cell infusion (moment 2), and 100 days after transplantation (moment 3). In each moment, oral changes were assigned scores and classified as mild, moderate, and severe risks. RESULTS: The most frequent pathological conditions were gingivitis, pericoronitis in the third molar region, and ulcers at the third moment assessments. However, at moments 2 and 3, the most common disease was mucositis associated with toxicity from the drugs used in the immunosuppression. CONCLUSION: Mucositis accounted for the increased score and potential risk of clinical complications. Gingivitis, ulcers, and pericoronitis were other changes identified as potential risk factors for clinical complications.


Assuntos
Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças da Boca/etiologia , Adolescente , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Estudos Prospectivos , Fatores de Risco
18.
An Bras Dermatol ; 89(4): 632-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25054751

RESUMO

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.


Assuntos
Células Dendríticas/patologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais/patologia , Mucosa Bucal/patologia , Antígenos CD/imunologia , Apoptose , Biópsia , Contagem de Células , Doença Crônica , Células Dendríticas/imunologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Humanos , Imuno-Histoquímica , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Masculino , Mucosa Bucal/imunologia , Estatísticas não Paramétricas , Adulto Jovem
19.
An. bras. dermatol ; 89(4): 632-637, Jul-Aug/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-715521

RESUMO

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.


Assuntos
Feminino , Humanos , Masculino , Adulto Jovem , Células Dendríticas/patologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas , Células Matadoras Naturais/patologia , Mucosa Bucal/patologia , Apoptose , Antígenos CD/imunologia , Biópsia , Contagem de Células , Doença Crônica , Células Dendríticas/imunologia , Doença Enxerto-Hospedeiro/imunologia , Imuno-Histoquímica , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Mucosa Bucal/imunologia , Estatísticas não Paramétricas
20.
An Bras Dermatol ; 88(5): 799-802, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24173188

RESUMO

Graft-versus-host disease is observed mainly in recipients of hematopoietic cell transplantation and is expressed by cutaneous or systemic signals and symptoms. Graft-versus-host disease is clinically classified as acute or chronic. Chronic Graft-versus-host disease occurs in up to 70% of hematopoietic cell transplanted patients and its clinical manifestations have important impact on morbidity and quality of life. The authors report an expressive cutaneous, oral and adnexal involvement in a patient with chronic Graft-versus-host disease with multiple lesions of lichenoid and atrophic pattern.


Assuntos
Doença Enxerto-Hospedeiro/patologia , Erupções Liquenoides/patologia , Pele/patologia , Atrofia , Transplante de Medula Óssea/efeitos adversos , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade
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