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Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. IV: CAR-T cell therapy for multiple myeloma patients
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Maiolino, Angelo

; Costa, Luciano J

; Pasquini, Marcelo

; Crusoe, Edvan de Queiroz

; Vigorito, Afonso Celso

; Salvino, Marco Aurelio

; Seguro, Fernanda Salles

; Schmidt Filho, Jayr

; Hungria, Vania Tietsche de Moraes

Hematology, Transfusion and Cell Therapy

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2021, Volume 43 Supl. 2 Páginas 30 - 34

Resumo: En | Texto: En | PDF: En

ABSTRACT Extraordinary progress has been made over the last decade in the treatment of multiple myeloma with the incorporation of new drugs, particularly proteasome inhibitors, immunomodulators, and monoclonal antibodies. The combined use of innovative drugs, already in the first lines of treatment, has led to an expressive increase in the survival of these patients. However, the approach to relapse remains a great challenge, and the disease continues to be incurable. In this scenario, modern immunotherapy has gained the limelight, especially with its recent use of CAR-T cells in clinical trials, as in the case of multiple myeloma, having the BCMA as the primary target. The results are impactful in the treatment of multiple myeloma patients who have had multiple relapses and are triple- and penta-refractory. In this Consensus, we have brought together a group of experts in multiple myeloma to discuss and forward their recommendations for the future, which we hope is very near, incorporating the CAR-T in our country.

https://doi.org/10.1016/j.htct.2021.09.004

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease
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Pereira, Andréa Z

; Vigorito, Afonso Celso

; Almeida, Alessandro de Moura

; Candolo, Alexandre de Almeida

; Silva, Ana Carolina Leão

; Brandão-Anjos, Ana Elisa de Paula

; Sá, Bianca Laselva de

; Souza, Catarina Lôbo Santos de

; Castro Junior, Cláudio Galvão de

; Oliveira, José Salvador Rodrigues de

; Barban, Juliana Bernardo

; Mancilha, Elaine Maria Borges

; Todaro, Juliana

; Lopes, Lilian Pinheiro

; Macedo, Maria Cristina Martins de Almeida

; Rodrigues, Morgani

; Ribeiro, Paulo Cesar

; Silva, Roberto Luiz da

; Roberto, Telma Sigolo

; Rodrigues, Thays de Cássia Ruiz

; Colturato, Vergilio Antonio Rensi

; Paton, Eduardo José de Alencar

; Barros, George Maurício Navarro

; Almeida, Rosana Ducatti Souza

; Moreira, Maria Claudia Rodrigues

; Flowers, Mary Evelyn

einstein (São Paulo)

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2020, Volume 18 elocation eAE4799

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

RESUMO O Consenso Brasileiro de Nutrição no Transplante de Células Tronco Hematopoiéticas: doença do enxerto contra o hospedeiro foi aprovado pela Sociedade Brasileira de Transplante de Medula Óssea, com a participação de 26 centros brasileiros de transplante de células-tronco hematopoiéticas. O Consenso descreve as principais condutas nutricionais em casos de doença do enxerto contra o hospedeiro, a principal complicação do transplante de células-tronco hematopoiéticas.

ABSTRACT The Brazilian Consensus on Nutrition in Hematopoietic Stem Cell Transplantation: Graft- versus -host disease was approved by Sociedade Brasileira de Transplante de Medula Óssea , with the participation of 26 Brazilian hematopoietic stem cell transplantation centers. It describes the main nutritional protocols in cases of Graft- versus -host disease, the main complication of hematopoietic stem cell transplantation.

https://doi.org/10.31744/einstein_journal/2020ae4799 1552 downloads

Hematopoietic stem cell mobilization for autologous transplantation in multiple myeloma patients previously exposed to cyclophosphamide, thalidomide, and dexamethasone: is granulocyte-colony stimulating factor alone enough?
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Vigorito, Afonso Celso

Revista Brasileira de Hematologia e Hemoterapia

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Dez 2016, Volume 38 Nº 4 Páginas 281 - 282

Resumo: En | Texto: En | PDF: En

https://doi.org/10.1016/j.bjhh.2016.07.006 551 downloads

Acute and chronic Graft-versus-host disease after hematopoietic stem cell transplantation
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Funke, Vaneuza A. M.

; Moreira, Maria Claudia Rodrigues

; Vigorito, Afonso Celso

Revista da Associação Médica Brasileira

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Out 2016, Volume 62 Supl. 1 Páginas 44 - 50

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

RESUMO A doença do enxerto contra hospedeiro (DECH) é uma das principais complicações do transplante de células-tronco Hematopoéticas, acometendo cerca de 50% a 80% dos pacientes. A DECH aguda e suas manifestações clínicas são discutidas neste artigo, bem como a classificação revisada do NIH para diagnóstico e classificação da DECH crônica. A terapêutica para DECH aguda e crônica é um importante campo de discussão uma vez que não há superioridade comprovada para a maioria das terapêuticas utilizadas após o tratamento primário. Assim, esta revisão pretende ser instrumento de consulta para hematologistas transplantadores que lidam com esta complexa complicação do procedimento.

ABSTRACT graft-versus-host disease (GVHD) is one of the main complications of hematopoietic stem cell transplantation, affecting about 50% to 80% of the patients. Acute GVHD and its clinical manifestations are discussed in this article, as well as the new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both chronic and acute GVHD is an important field of discussion, as there is no proven superiority for the majority of therapies used after primary treatment has failed. Hence, this review is meant to be a useful consultation tool for hematologists dealing with this complex transplantation procedure complication.

https://doi.org/10.1590/1806-9282.62.suppl1.44 6326 downloads

Association between human leukocyte antigens and graft-versus-host disease occurrence after allogenic hematopoietic stem cell transplantation
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Cardozo, Daniela Máira

; Lieber, Sofia Rocha

; Marques, Silvia Barbosa Dutra

; Aranha, Francisco José

; Vigorito, Afonso Celso

; Souza, Cármino Antonio de

; Visentainer, Jeane Eliete Laguila

Sao Paulo Medical Journal

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2012, Volume 130 Nº 4 Páginas 219 - 224

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

CONTEXTO E OBJETIVO: A doença do enxerto contra o hospedeiro (DECH) é uma das complicações pós-transplante alogênico de células progenitoras hematopoéticas. Este estudo investigou uma associação entre o antígeno leucocitário humano (HLA) e a ocorrência de DECH aguda e crônica, em pacientes que receberam transplantes de irmãos HLA-idênticos. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo no Centro de Hematologia e Hemoterapia da Universidade Estadual de Campinas (Unicamp). MÉTODOS: Os participantes foram 176 pacientes cujo primeiro transplante foi entre 1997 e 2009. A tipagem HLA foi realizada por sorologia e reação em cadeia da polimerase (PCR) com sequência específica de primers. RESULTADOS: A DECH aguda foi associada positivamente com HLA-A10 (P = 0,0007), HLA-A26 (P = 0,002), B55 (P = 0,001), DRB1*15 (P = 0,0211) e DQB1*05 (P = 0,038), enquanto HLA-B16 (P = 0,0333) foi mais frequente em pacientes sem DECH aguda. A DECH crônica foi associada positivamente com HLA-A9 (P = 0,01) e A23 (P = 0,0292) e, negativamente, com HLA-A2 (P = 0,0031) e B53 (P = 0,0116). HLA-B35 (P = 0,0373), B49 (P = 0,0155) e B55 (P = 0,0024) estavam aumentados em pacientes com DECH aguda grau 3 ou maior, em comparação aos outros pacientes. Em pacientes com DECH crônica extensa, HLA-A9 (P = 0,0004), A24 (P = 0,0059) e A26 (P = 0,0411) estavam aumentados em comparação aos outros pacientes, enquanto HLA-A2 estava diminuído (P = 0,0097). CONCLUSÕES: Este estudo sugere que o HLA pode influenciar a ocorrência de DECH aguda e crônica e a sua gravidade. No entanto, um estudo com melhor desenho e com mais pacientes será necessário para confirmar esses resultados.

CONTEXT AND OBJECTIVE: Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings. DESIGN AND SETTING: Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp). METHODS: The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence. RESULTS: Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097). CONCLUSION: This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.

4690 downloads

Functional evaluation indicates physical losses after hematopoietic stem cell transplantation
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Souza, Clarissa Vasconcellos de

; Miranda, Eliana Cristina Martins

; Garcia Jr, Celso

; Aranha, Francisco José Penteado

; Souza, Cármino Antonio de

; Vigorito, Afonso Celso

Revista Brasileira de Hematologia e Hemoterapia

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2012, Volume 34 Nº 5 Páginas 345 - 351

Resumo: En | Texto: En | PDF: En

OBJECTIVE: To perform a function evaluation of patients before and after hematopoietic stem cell transplantation. METHODS: From November 2008 to November 2010, 29 female (58%) and 21 male patients (42%) with median age of 48 years (range: 24-67) were enrolled in this study. Data collection was performed before and after autologous or allogeneic hematopoietic stem cell transplantation. Evaluation instruments included the 2-minute walking test to evaluate gait performance with assessment of the oxygen saturation, heart rate and Borg Scale before and after the test; grip strength for strength evaluation, Schober Test for spine mobility testing and maximum and adapted activity scores of the Human Activity Profile questionnaire to test functionality in daily activities. RESULTS: Fifty patients were evaluated at baseline; six did not undergo hematopoietic stem cell transplantation (three died, one refused and two were excluded). Thus 44/50 (88% - 21 allogeneic and 23 autologous) transplantations were performed. Only 33 of the 44 patients (75%) performed evaluations after transplantation (nine died and two were excluded). Of the patients who performed both evaluations, significantly lower values were found in the evaluation after transplantation for the 2-minute walking test (p-value = 0.004), grip strength of both right and left hands (p-value = 0.004 and p-value < 0.0001, respectively), the Schober Test, and maximum and adapted activity scores (p-value < 0.0001). The heart rate was higher (p-value = 0.01) before the 2-minute walking test and oxygen saturation was higher (p-value = 0.02) after. CONCLUSION: Statistical differences indicate functional impairment after transplantation showing physical losses in this population.

https://doi.org/10.5581/1516-8484.20120090 1833 downloads Citado 1 vez em SciELO

Brazilian experience using high dose sequential chemotherapy followed by autologous hematopoietic stem cell transplantation for malignant lymphomas
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Duarte, Bruno Kosa Lino

; Miranda, Eliana Cristina Martins

; Nucci, Marcio

; Vigorito, Afonso Celso

; Penteado, Francisco José

; Marques Jr, José Francisco Comenalli

; Oliveira-Duarte, Gislaine Borba

; Lorand-Metze, Irene Gyongyver Heidemarie

; Pagnano, Katia Borgia

; Delamain, Marcia Torresan

; Baldissera, Renata

; Valente, Isabella Salvetti

; Souza, Carmino Antonio de

Revista Brasileira de Hematologia e Hemoterapia

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Dez 2011, Volume 33 Nº 6 Páginas 432 - 438

Resumo: En | Texto: En | PDF: En

OBJECTIVE: To evaluate the use of high-dose sequential chemotherapy in a Brazilian population. METHODS: High-dose cyclophosphamide followed by autologous hematopoietic stem cell transplantation is an effective and feasible therapy for refractory/relapsed lymphomas; this regimen has never before been evaluated in a Brazilian population. All patients (106 with high-grade non-Hodgkin lymphoma and 77 with Hodgkin's lymphoma) submitted to this treatment between 1998 and 2006 were analyzed. Chemotherapy consisted of the sequential administration of high-dose cyclophosphamide (4 or 7 g/m²) and granulocyte-colony stimulating factor (300 µg/day), followed by peripheral blood progenitor cell harvesting, administration of etoposide (2g/m²) and methotrexate (8 g/m² only for Hodgkin's lymphoma) and autologous hematopoietic stem cell transplantation. RESULTS: At diagnosis, non-Hodgkin lymphoma patients had a median age of 45 (range: 8-65) years old, 78% had diffuse large B-cell lymphoma and 83% had stage III/IV disease. The Hodgkin's lymphoma patients had a median age of 23 (range: 7-68) years old, 64.9% had the nodular sclerosis subtype and 65% had stage III/IV disease. Nine Hodgkin's lymphoma patients (13%) and 10 (9%) non-Hodgkin lymphoma patients had some kind of cardiac toxicity. The overall survival, disease-free survival and progression-free survival in Hodgkin's lymphoma were 29%, 59% and 26%, respectively. In non-Hodgkin lymphoma, these values were 40%, 49% and 31%, respectively. High-dose cyclophosphamide-related mortality was 10% for Hodgkin's lymphoma and 5% for non-Hodgkin lymphoma patients. High-dose cyclophosphamide dosing had no impact on toxicity or survival for both groups. CONCLUSIONS: Despite a greater prevalence of poor prognostic factors, our results are comparable to the literature. The incidence of secondary neoplasias is noteworthy. Our study suggests that this approach is efficient and feasible, regardless of toxicity-related mortality.

https://doi.org/10.5581/1516-8484.20110118 1917 downloads

Brazilian workshop model to train investigators in chronic graft-versus-host disease clinical trials according to the 2005-2006 National Institutes of Health recommendations
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Tavares, Rita de Cássia Barbosa da Silva

; Silva, Márcia de Matos

; Bouzas, Luis Fernando da Silva

; Rodrigues, Maria Cláudia

; Vigorito, Afonso Celso

; Funke, Vaneusa

; Mauad, Marcos

; Correa, Maria Elvira Pizzigatti

; Souza, Clarissa Vasconcellos de

; Nunes, Elenaide

; Ferrari, Alessandra

; Paixão, Ariana

; Martins, Talita

; Pallottino, Érika

; Flowers, Mary Evelyn Dantas

Revista Brasileira de Hematologia e Hemoterapia

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Out 2011, Volume 33 Nº 5 Páginas 358 - 366

Resumo: En | Texto: En | PDF: En

BACKGROUND: The lack of standardization of clinical diagnostic criteria, classification and severity scores of chronic graft-versus-host disease led the National Institutes of Health to propose consensus criteria for the purpose of clinical trials. METHODS: Here we describe a one-day workshop model conducted by the Chronic Graft-versus-Host Disease Brazil-Seattle Consortium Study Group to train investigators interested in participating in multicenter clinical trials in Brazil. Workshop participants included eight transplant physicians, one dermatologist, two dentists, three physical therapists and one psychologist from five institutions. Workshop participants evaluated nine patients with varying degrees of severity of mucocutaneous lesions and other manifestations of the disease followed by a training session to review and discuss the issues encountered with the evaluation and scoring of patients and in the methods used to evaluate grip strength and the 2-minute walk test. RESULTS: Most participants had difficulties in rating the percentage of each type of mucocutaneous lesion and thought 20 minutes was insufficient to evaluate and record the scores of each patient using the National Institutes of Health criteria and other cutaneous assessments. Several specific areas of difficulties encountered by the evaluators were: 1) determining the percentage of erythema in movable and non-movable sclerosis, 2) whether to score all cutaneous findings in a particular area or just the dominant lesion; 3) clarification of the definition of poikiloderma in chronic graft-versus-host disease; 4) discrepant interpretation of the mouth score and 5) clarification on the methodology used for the evaluation of grip strength and the 2-minute walk tests. CONCLUSIONS: Results of this workshop support the need to train investigators participating in clinical trials on chronic graft-versus-host disease.

https://doi.org/10.5581/1516-8484.20110099 6075 downloads

Monitoring of BCR-ABL levels in chronic myeloid leukemia patients treated with imatinib in the chronic phase: the importance of a major molecular response
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Machado, Melissa Pereira

; Tomaz, Juarez Pires

; Lorand-Metze, Irene

; Souza, Cármino Antonio de

; Vigorito, Afonso Celso

; Delamain, Marcia Torresan

; Bendit, Israel

; Pereira, Noemi Farah

; Pagnano, Katia Borgia Barbosa

Revista Brasileira de Hematologia e Hemoterapia

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Jun 2011, Volume 33 Nº 3 Páginas 211 - 215

Resumo: En | Texto: En | PDF: En

BACKGROUND: Real time PCR has become the most common technique to monitor BCR-ABL transcript levels of patients treated with kinase inhibitors. The aim of this study was to evaluate BCR-ABL levels of chronic myeloid leukemia patients treated with imatinib in the chronic phase and correlate the response to therapy and event-free survival. METHODS: BCR-ABL levels were measured in peripheral blood cell samples using Real time PCR at diagnosis and then every 3 months after starting therapy with imatinib. Major molecular response was defined as a three-log reduction from the standardized baseline value. Major molecular response values were adjusted to international scale using a conversion factor of 1.19. The results are reported as a BCR-ABL/ABL ratio (%). RESULTS: Hematological, major cytogenetic and complete cytogenetic responses were achieved by 57 (95%), 45 (75%) and 38 (63%) patients, respectively. Twenty-four out of sixty patients achieved a major molecular response (40%) in a median time of 8.5 months. Overall survival and event free survival were higher for patients with (100%) versus patients without (77%) a complete cytogenetic response (p-value = 0.01) at 48 months. Patients with complete cytogenetic response and major molecular response had a higher event free survival compared to patients with complete cytogenetic response but without major molecular response (p-value = 0.007). CONCLUSION: In conclusion, the prognostic impact of achieving complete cytogenetic response and a major molecular response and also the importance of molecular monitoring in the follow-up of chronic myeloid leukemia patients were demonstrated.

https://doi.org/10.5581/1516-8484.20110056 4023 downloads Citado 2 vezes em SciELO

10.

A multicenter feasibility study of chronic graft-versus-host disease according to the National Institute of Health criteria: efforts to establish a Brazil-Seattle consortium as a platform for future collaboration in clinical trials
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Vigorito, Afonso Celso

; Bouzas, Luis Fernando da Silva

; Moreira, Maria Cláudia Rodrigues

; Funke, Vaneuza Araújo Moreira

; Colturato, Virgílio Antonio Rensi

; Pedro, Andréia

; Souza, Clarissa Vasconcellos de

; Nunes, Elenaide Coutinho

; Miranda, Eliana Cristina Martins

; Camacho, Kátia

; Mauad, Marcos Augusto

; Correa, Maria Elvira Pizzigatti

; Silva, Márcia de Matos

; Sousa, Mair Pedro de

; Tavares, Rita de Cássia Barbosa da Silva

; Lee, Stephanie Joi

; Flowers, Mary Evelyn Dantas

Revista Brasileira de Hematologia e Hemoterapia

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2011, Volume 33 Nº 4 Páginas 283 - 289

Resumo: En | Texto: En | PDF: En

BACKGROUND: New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. OBJECTIVES: The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. METHODS: The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. RESULTS: Of the 34 patients, 26 (76%) met the criteria of overlap syndrome and eight (24%) the classic subcategory. The overall severity of disease was moderate in 21 (62%) and severe in 13 (38%) patients. The median time from transplant to onset of chronic graft-versus-host disease was 5.9 months (Range: 3 - 16 months); the median time for the overlap syndrome subcategory was 5.9 months (Range: 3 - 10 months) and for the classic subcategory, it was 7.3 months (Range: 3 - 16 months). At a median follow up of 16.5 months (Range: 4 - 39 months), overall survival was 75%. CONCLUSIONS: It was feasible to use the National Institute of Health consensus criteria for the diagnosis and scoring of chronic graft-versus-host disease in a Brazilian prospective multicenter study. More importantly, a collaborative hematopoietic cell transplantation network was established in Brazil offering new opportunities for future clinical trials in chronic graft-versus-host disease and in other areas of research involving hematopoietic stem cell transplantation.

https://doi.org/10.5581/1516-8484.20110078 2365 downloads

11.

Valor prognóstico da tomografia computadorizada de seios paranasais no transplante de células-tronco hematopoiéticas
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Ortiz, Erica

; Nakamura, Érika

; Magalhães, Rodrigo

; Souza, Cármino Antonio de

; Chone, Carlos Takahiro

; Vigorito, Afonso Celso

; Sakano, Eulalia

Brazilian Journal of Otorhinolaryngology

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Out 2010, Volume 76 Nº 5 Páginas 618 - 622

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

O transplante de células-tronco hematopoiéticas (TCTH) causa imunossupressão e predispõe ao desenvolvimento de rinossinusites. A realização de tomografia computadorizada (TC) de seios paranasais pode auxiliar no diagnóstico de rinossinusopatias nestes pacientes, porém a realização em todos estes pacientes é questionável. OBJETIVO: Verificar a necessidade de realizar a TC nos candidatos ao TCTH e relacionar as alterações tomográficas encontradas a rinossinusopatias pós TCTH. MÉTODO: Estudo piloto prospectivo em que as TC de seios paranasais foi executado antes e após o TCTH e avaliado conforme classificação de Lund e Mackay. RESULTADOS: Foram obtidos 77,5% e 61% de TC normais no pré e pós-TCTH, respectivamente. O estádio tomográfico pré-TCTH não se relacionou à ocorrência de rinossinusite após o TCTH. As variações anatômicas encontradas (19,4%) não se relacionaram com a ocorrência de rinossinusite, mas sim com a gravidade da rinossinusite no pós-TCTH. Não houve associação significativa entre estadiamento tomográfico prévio e desenvolvimento de rinossinusite pós-TCTH. CONCLUSÃO: Não há necessidade de realização de tomografia computadorizada de seios paranasais em todos os pacientes previamente ao TCTH; e a variação anatômica não predispõe à rinossinusite nem antes nem após o transplante de medula óssea, apenas pode agravar a evolução da rinossinusite após o TCTH.

Hematopoietic Stem Cell Transplant (HSCT) causes immunosuppression and predisposition to sinusitis. CT scans are complementary exams used in the diagnosis of sinusitis; however, its use in every patient is questionable. AIM: to check the usefulness of ordering a CT scan prior to HSCT and to study the relationship between anatomical variations and sinusitis. METHOD: prospective study in which we performed paranasal CT scans before and after HSCT, using the Lund and Mackay score. RESULTS: 77.5% and 61% of CT scans showed no evidence of sinus disease before and after HSCT. CT staging was not associated with sinusitis after HSCT. Anatomical variations were related to radiographic disease severity, but not to development of sinusitis after HSCT. There was no relation between pre-CT staging and sinusitis after BMT. CONCLUSION: CT scans are not useful for all patients before HSCT. Anatomical variation is not a predictive feature to sinusitis but it can determine its severity.

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12.

Leucemia mieloide crônica e outras doenças mieloproliferativas crônicas
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Funke, Vaneuza M.

; Bitencourt, Henrique

; Vigorito, Afonso Celso

; Aranha, Francisco José

Revista Brasileira de Hematologia e Hemoterapia

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Mai 2010, Volume 32 Supl. 1 Páginas 71 - 90

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

A leucemia mieloide crônica (LMC) é uma doença clonal da medula óssea caracterizada pela presença do cromossomo Philadelphia (Ph), resultante da translocação entre os cromossomos 9 e 22. O gene híbrido assim formado, BCR-ABL codifica proteínas com atividade de tirosinoquinases que regulam o crescimento celular. A partir da década de 80, o transplante alogênico de células-tronco hematopoéticas (TCTH) se tornou tratamento de escolha para pacientes com idade menor que 55 anos de idade e doador compatível. Não obstante, a partir do advento dos inibidores de tirosinoquinases, drogas de alta eficácia e baixa toxicidade, houve uma mudança no algoritmo de tratamento da LMC. As indicações do TCTH foram restritas em decorrência da mortalidade relacionada a este procedimento e o mesilato de imatinibe tornou-se o novo tratamento de escolha para esta enfermidade. No Brasil e possivelmente em outros países em desenvolvimento, as condições socioeconômicas fazem com que o TCTH ainda seja considerado como primeira linha de tratamento em algumas situações. O TCTH permanece indicado nas doenças (ou neoplasias) mieloproliferativas, como a mielofibrose primária em situações de alto risco e pacientes portadores de policitemia vera ou trombocitose essencial que tenham evoluído para mielofibrose com características de alto risco.

Chronic myeloid leukemia (CML) is a clonal disease of the bone marrow characterized by the presence of Philadelphia chromosome (Ph) which results from translocation between chromosome nine and 22. The hybrid gene, BCR-ABL, encodes proteins with tyrosine kinase activity that regulate cell growth. From the 80´s allogeneic hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for patients younger than 55 years of age and donor. However, from the advent of tyrosine kinase inhibitors, drugs of high efficacy and low toxicity, there was a change in the treatment algorithm of CML. The indications of HSCT have been restricted as a result of mortality related to this procedure and imatinib mesylate has become the new treatment of choice for this disease. In Brazil and possibly in other developing countries, socio-economic conditions make HSCT still feasible as first-line treatment in some situations. The HSCT remains indicated for Ph negative myeloproliferative disorders such as high risk myelofibrosis or patients with polycythemia vera or essential thrombocytosis that have evolved to myelofibrosis with high-risk features.

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13.

Renda e qualidade de vida (QV) devem ser valorizadas no transplante de células-tronco hematopoéticas
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Vigorito, Afonso Celso

Revista Brasileira de Hematologia e Hemoterapia

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2010, Volume 32 Nº 2 Páginas 95 - 96

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14.

Influência do imatinibe no resultado do TMO e sua eficácia no tratamento da recaída
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Vigorito, Afonso Celso

Revista Brasileira de Hematologia e Hemoterapia

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Abr 2008, Volume 30 Supl. 1 Páginas 47 - 51

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

O mesilato de imatinibe (MI) tornou-se o tratamento de primeira linha para os pacientes com leucemia mielóide crônica (LMC). O transplante de células-tronco hematopoiéticas (TCTH) alogênico tem sido utilizado como tratamento de salvamento para os pacientes que são intolerantes ao MI, falham na obtenção da resposta citogenética completa (RCC) ou recidivam. A primeira parte desta revisão discutirá a influência do uso do MI pré-transplante nos resultados do transplante e o impacto da resposta subótima, ou perda da resposta, na sobrevida após o transplante, nos pacientes em fase crônica. A segunda parte discutirá o manejo da recidiva pós-transplante. A infusão de linfócitos (DLI) tornou-se o tratamento de escolha para os pacientes que recidivam após o TCTH. A resposta ao DLI é dose dependente e a dose de células efetivas é influenciada pela quantidade, pela fase da recidiva e pelo grau de histocompatibilidade entre doador e receptor. O MI é agora uma alternativa ao DLI para a obtenção da remissão, sem o risco da doença do enxerto contra o hospedeiro (DECH), e pode ser efetivo quando o DLI for ineficaz. O MI pode também ser utilizado em combinação com o DLI para aumentar as respostas. O MI é seguro e bem tolerado em combinação com o DLI. Os pacientes atingem a resposta molecular completa mais rápida, são capazes de parar o MI sem apresentar recidiva molecular e a sobrevida livre de doença é maior.

Imatinib mesylate (IM) has become the first-line therapy for chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is increasingly chosen as salvage therapy for patients who are intolerant of IM, fail to achieve a complete cytogenetic response (CCR) or relapse. The first part of this review will discuss the effect of prior exposure to IM on transplant outcomes and the impact of a poor or a loss of response at the time of transplantation on post-transplantation survival of patients who underwent transplantation in a chronic phase (CP). The second part will discuss the management of relapse disease after transplant. Donor lymphocyte infusion (DLI) has become the treatment of choice for patients who relapse. The response to DLI is dose-dependent and the effective cell dose is influenced by the quantity and phase of CML at relapse and degree of donor/recipient histocompatibility. IM is now an alternative to DLI as it can be used to achieve remission without graft-versus-host disease and may be effective when DLI has failed. It can also be used in combination with lower doses of DLI to maximize responses. IM is safe and well tolerated in combination with DLI, patients achieve molecular response more rapidly, are able to stop IM without recurrence of molecular disease and this treatment has a higher disease free survival rate after transplantation.

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15.

Associação entre HLA e leucemia em uma população brasileira de etnia mista
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Barion, Lúcia Aparecida

; Tsuneto, Luiza Tamie

; Testa, Giuliana Vitoriano

; Lieber, Sofia Rocha

; Persoli, Ligia Beatriz Lopes

; Marques, Silvia Barbosa Dutra

; Vigorito, Afonso Celso

; Aranha, Francisco José Penteado

; Eid, Katia Aparecida Brito

; Oliveira, Gislaine Borba

; Miranda, Eliana Cristina Martins

; Souza, Cármino Antonio de

; Visentainer, Jeane Eliete Laguila

Revista da Associação Médica Brasileira

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Jun 2007, Volume 53 Nº 3 Páginas 252 - 256

Resumo: Pt En | Texto: Pt En | PDF: Pt | PDF: En

OBJETIVOS: O objetivo deste estudo foi investigar a freqüência de antígenos HLA Classe I e de alelos HLA Classe II em 164 pacientes com vários tipos de leucemias: 35 pacientes com LLA (leucemia linfóide aguda), 50 com LMA (leucemia mielóide aguda) e 78 com LMC (leucemia mielóide crônica). MÉTODOS: A tipagem HLA Classe I foi realizada por microlinfocitotoxicidade e a de Classe II por PCR-SSP (polymerase chain reaction - sequence specific of primers), ambas da One Lambda (Canoga Park, CA, US). RESULTADOS: Em pacientes com LLA, as freqüências das variantes HLA-B45 e HLA-B56 foram maiores (P = 0,02; OR = 3,13; 95%IC = 0,94-10,44; P = 0,03; OR = 3,61; 95%IC = 0,47-27,64, respectivamente), quando comparadas com controles. Nos pacientes com LMA, a freqüência de HLA-B7 (P = 0,01; OR = 2,41; 95%IC = 1,25-4,67) foi maior que em controles. A presença de HLA-B45 (P= 0,01; OR = 3,29; 95%IC = 1,46-7,40) e de HLA-DRB1*04 (P = 0,002; OR = 2,17; 95%IC = 1,36-3,46) e HLA-DRB1*08 (P = 0,004; OR = 2,36; 95%IC = 1,34-4,16) foi associada ao maior risco de desenvolver LMC. CONCLUSÃO: Nossos resultados sugerem que variantes HLA conferem susceptibilidade a algumas formas de leucemia e podem prover novas ferramentas para a investigação da genética e etiologia desta doença.

OBJECTIVE: The main purpose of this study was to investigate the class I HLA antigens and class II HLA allele frequencies in 164 patients with leukemia: 35 patients with ALL (acute lymphoid leukemia), 50 with AML (acute myeloid leukemia) and 78 with CML (chronic myeloid leukemia). METHODS: The genotyping of class I HLA was performed by microlymphocytotoxicity and of class II by PCR-SSP (polymerase chain reaction - sequence specific of primers) (One Lambda, Canoga Park, CA, USA). RESULTS: In patients with LLA, frequencies of HLA-B45 and HLA-B56 were higher (P = 0.02; OR = 3.13; 95%IC = 0.94-10.44; P = 0.03; OR = 3.61; 95%IC = 0.47-27.64, respectively), than in controls. In patients with AML, the frequency of HLA-B7 (P = 0.01; OR = 2.41; 95%IC = 1.25-4.67) was higher than in controls. The presence of HLA-B45 (P= 0.01; OR = 3.29; 95%IC = 1.46-7.40), HLA-DRB1*04 (P = 0.002; OR = 2.17; 95%IC = 1.36-3.46) and HLA-DRB1*08 (P = 0.004; OR = 2.36; 95%IC = 1.34-4.16) was associated to increased risk of CML developing. CONCLUSION: Our results suggest that variants of HLA confer susceptibility to the same forms of leukemia, and could provide new tools for the investigation of genetics and etiology of this disease.

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