HEMATOPOIETIC STEM CELL TRANSPLANTATION AND CROHN'S DISEASE: POSITION PAPER FROM THE TRANSPLANTATION COMMITTEE OF THE BRAZILIAN GROUP FOR THE STUDY OF INFLAMMATORY BOWEL DISEASES (GEDIIB).

Crohn's disease (CD) is a relapse-remitting inflammatory bowel disease that can affect any part of the digestive system. This heterogeneous disease has multiple factors that contribute to an abnormal immune response to intestinal microorganisms. Treatment is based on the use of anti-inflammatories, corticosteroids, immunosuppressants and biologic biologic agents either alone or in combination. Surgical treatment is usual and, ten years after diagnosis, more than 80% of patients report having undergone surgical procedures related to the disease. Unfortunately, none of the treatments described offer a cure, and many cases become refractory or without therapeutic options. In this scenario, hematopoietic stem cell transplantation has been suggested because clinical remission was obtained in patients who had CD associated with malignant hematological diseases and an alternative since the first reports in 2010. In this report, the Transplantation Committee of the Brazilian Group for the Study of Inflammatory Bowel Diseases reviews the history and results of the procedure in patients with CD, detailing and discussing the various relevant points that permeate hematopoietic stem cell transplantation and cell therapy in this disease.

Transplante de células tronco hematopoiéticas e doença de Crohn: posição do Comitê de Transplantes do Grupo Brasileiro para estudo das doenças inflamatórias do intestino (GEDIIB) / Hematopoietic stem cell transplantation and crohn's disease: position paper from the transplantation committee of the brazilian group for the study of inflammatory bowel diseases (gediib)

ABSTRACT Crohn's disease (CD) is a relapse-remitting inflammatory bowel disease that can affect any part of the digestive system. This heterogeneous disease has multiple factors that contribute to an abnormal immune response to intestinal microorganisms. Treatment is based on the use of anti-inflammatories, corticosteroids, immunosuppressants and biologic biologic agents either alone or in combination. Surgical treatment is usual and, ten years after diagnosis, more than 80% of patients report having undergone surgical procedures related to the disease. Unfortunately, none of the treatments described offer a cure, and many cases become refractory or without therapeutic options. In this scenario, hematopoietic stem cell transplantation has been suggested because clinical remission was obtained in patients who had CD associated with malignant hematological diseases and an alternative since the first reports in 2010. In this report, the Transplantation Committee of the Brazilian Group for the Study of Inflammatory Bowel Diseases reviews the history and results of the procedure in patients with CD, detailing and discussing the various relevant points that permeate hematopoietic stem cell transplantation and cell therapy in this disease.

RESUMO A doença de Crohn (DC) é uma doença inflamatória intestinal (DII) recidivante recorrente que pode afetar qualquer parte do sistema digestivo. É doença heterogênea e possui múltiplos fatores que contribuem para uma resposta imune anormal aos microrganismos intestinais. O tratamento baseia-se no uso de anti-inflamatórios, corticosteroides e imunossupressores e imunobiológicos que são utilizados isoladamente ou em combinação. O tratamento cirúrgico é frequente e 10 anos após o diagnóstico, mais de 50% dos pacientes relatam terem sido submetidos a procedimentos cirúrgicos relacionados à doença. Infelizmente, nenhum dos tratamentos descritos oferece cura, e inúmeros casos tornam-se refratários ou sem opções terapêuticas. Nesse cenário, o transplante de células-tronco hematopoéticas (TCTH) em decorrência da remissão clínica de pacientes que apresentavam DC associada a doenças hematológicas malignas, passou a ser alternativa desde os primeiros resultados em 2010. Neste relato, a Comissão de Transplantes do Grupo Brasileiro de Estudo das Doenças Inflamatórias Intestinais revisa a história e os resultados do procedimento em pacientes com DC, detalhando e discutindo os diversos pontos relevantes que permeiam o TCTH e a terapia celular no tratamento da moléstia.

Allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders

BACKGROUND: The role of allogeneic hematopoietic stem cell transplantation for advanced indolent lymphoproliferative disorders remains to be established. OBJECTIVE: This paper aims to describe the results of allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders. METHODS: This article reports on 29 adult patients submitted to allogeneic transplantations from 1997 to 2010. RESULTS: Most had follicular non-Hodgkin lymphoma (n = 14) or chronic lymphocytic leukemia (n = 12). The median age was 44 years (range: 24-53 years) and 65% of patients were male. Only 21% had had access to rituximab and 45% to fludarabine. All had advanced disease (stage IV) with partial response or stable disease. Most underwent myeloablative conditioning n = 17 - 59%). In this scenario, refractory disease was observed in seven (24%) patients, the 100-day mortality rate was 17% (n = 5) and relapse occurred in four patients (18%). The main cause of death throughout the follow up was refractory disease in six of the 12 patients who died. Moderate and severe chronic graft-versus-host disease was frequent; about 41% of 24 patients analyzed. The overall survival rates and disease free survival at 42 months were 56.7% and 45.4%, respectively. According to Kaplan-Meyer analysis, the median time from diagnosis to transplant predicted the overall survival; however age, gender and conditioning regimen did not predict the prognosis. It was impossible to reach other conclusions because of the small sample size in this study. CONCLUSIONS: The role of allogeneic transplantations should be re-evaluated in the era of targeted therapy.

Allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders.

BACKGROUND: The role of allogeneic hematopoietic stem cell transplantation for advanced indolent lymphoproliferative disorders remains to be established. OBJECTIVE: This paper aims to describe the results of allogeneic hematopoietic stem cell transplantation in patients with advanced indolent lymphoproliferative disorders. METHODS: This article reports on 29 adult patients submitted to allogeneic transplantations from 1997 to 2010. RESULTS: Most had follicular non-Hodgkin lymphoma (n=14) or chronic lymphocytic leukemia (n=12). The median age was 44 years (range: 24-53 years) and 65% of patients were male. Only 21% had had access to rituximab and 45% to fludarabine. All had advanced disease (stage IV) with partial response or stable disease. Most underwent myeloablative conditioning n=17-59%). In this scenario, refractory disease was observed in seven (24%) patients, the 100-day mortality rate was 17% (n=5) and relapse occurred in four patients (18%). The main cause of death throughout the follow up was refractory disease in six of the 12 patients who died. Moderate and severe chronic graft-versus-host disease was frequent; about 41% of 24 patients analyzed. The overall survival rates and disease free survival at 42 months were 56.7% and 45.4%, respectively. According to Kaplan-Meyer analysis, the median time from diagnosis to transplant predicted the overall survival; however age, gender and conditioning regimen did not predict the prognosis. It was impossible to reach other conclusions because of the small sample size in this study. CONCLUSIONS: The role of allogeneic transplantations should be re-evaluated in the era of targeted therapy.