Hepatic veno-occlusive disease(VOD), also known as sinusoidal obstruction syndrome, is a major complication of hematopoietic stem cell transplantation and it carries a high mortality. Prophylaxis for hepatic VOD is co...Hepatic veno-occlusive disease(VOD), also known as sinusoidal obstruction syndrome, is a major complication of hematopoietic stem cell transplantation and it carries a high mortality. Prophylaxis for hepatic VOD is commonly given to transplant recipients from the start of conditioning through the early weeks of transplant. However, high quality evidence from randomized controlled trials is scarce with small sample sizes and the trials yielded conflicting results. Although various treatment options for hepatic VOD are available, most have not undergone stringent evaluation with randomized controlled trial and therefore it remains uncertain which treatment offers real benefit. It remains controversial whether VOD prophylaxis should be given, which prophylactic therapy should be given, who should receive prophylaxis, and what treatment should be offered once VOD is established.展开更多
Background: The unavoidable links between the benefits of conventional systemic treatment of cancer and the side effects such as lymphopenia. Objective: To analyze this phenomenon in view of the newly discovered troph...Background: The unavoidable links between the benefits of conventional systemic treatment of cancer and the side effects such as lymphopenia. Objective: To analyze this phenomenon in view of the newly discovered trophic function of circulating hematopoietic stem cells (HSC) and their lymphocyte descendants. Method: We used population statistics and recent current research involving natural aging and preliminary aging with cancer, its cytotoxic therapy, eclampsia at pregnancy, and radiation hormesis. Results: In contrast to immune-defense interpretations of these health conditions, the trophic influence of HSC and morphogenic lymphocytes on natural tissue renewal and regeneration after sublethal injuries eliminates the majority of covered inconsistencies, which are inherent to the dominating idea of cellular immunity. Conclusion: Our examination led to the feeding influence of lymphopoiesis on tumor progression, an indirect mechanism of tumor growth control by systemic therapy via either destruction of trophic cells, or by competitive distraction from malignant tissue via reparation of sublethal injuries in normal tissues. Analyses also involved similarities of the mechanisms of systemic chemotherapy and total body/half body radiotherapy in low doses, as well as the futility of the theoretical opposition of the radiation hormesis phenomenon to the linear non-threshold model, dominant in radiobiology.展开更多
Summary:It has been identified that malnutrition can influence the immune system and time of engraftment,and it's also associated with increased incidence of complications,prolonged length of hospital stays,and tr...Summary:It has been identified that malnutrition can influence the immune system and time of engraftment,and it's also associated with increased incidence of complications,prolonged length of hospital stays,and transplant mortality and morbidity in patients undergoing hematopoietic stem cell transplantation(HSCT),so dynamic nutrition care is highly important.The aim of this study was to better understand the differences between clinical nutrition practices and international recommendations as well as possible barriers to the use of nutrition support in HSCT patients.An evidence-based nutrition support pathway was constructed through a systematic literature review to identify evidence and recommendations relating to the relevant issues.Then,a questionnaire consisting of 28 questions that focused on the 4 topics,namely,assessment and screening for malnutrition,nutrition support interventions,nutrition support in gastrointestinal graft-ver5U5・host disease(GVHD)and neutropenic diet was developed by the study authors and used for data collection.Responses of 18 HSCT centers from 17 provinces were received.General assessment for malnutrition was performed at 72%(13/18)centers.Parenteral nutrition(PN)was given as the first option to HSCT patients in the majority of centers,despite the fact that current guidelines recommend enteral nutrition(EN)over PN.As many as 72%(13/18)of the centers considered a neutropenic diet in the management of HSCT patients,but only one center had a formal neutropenic diet protocol in place for transplant recipients.Criteria for initiating nutrition support in patients with gastrointestinal GVHD were heterogeneous among the centers,and PN was the most widely used technique.The survey results revealed significant heterogeneity with regard to nutrition support practices among the centers,as well as between the practices and the guidelines.Standard nutrition support guidelines or protocols for nutrition support practices were absent in most of the centers.展开更多
Crohn's disease(CD) is an inflammatory bowel disease that can affect any site of the digestive system. It occurs due to an immunological imbalance and is responsible for intestinal mucosal lesions and complication...Crohn's disease(CD) is an inflammatory bowel disease that can affect any site of the digestive system. It occurs due to an immunological imbalance and is responsible for intestinal mucosal lesions and complications such as fistulas and stenoses. Treatment aims to stabilize the disease, reducing the symptoms and healing intestinal lesions. Surgical procedures are common in patients. Cell therapy was initially used to treat this disease in patients who also suffered from lymphoma and leukemia and were considered to be good candidates for autologous and allogeneic transplantation. After transplantation, an improvement was also observed in their CD. In 2003, the procedure began to be used to treat the disease itself, and several case series and randomized studies have been published since then; this approach currently comprises a new option in the treatment of CD. However, considerable doubt along with significant gaps in our knowledge continue to exist in relation to cell therapy for CD. Cell therapy is currently restricted to the autologous modality of hematopoietic stem cell transplantation and, experimentally, to mesenchymal stromal cells to directly treat lesions of the anal mucosa. This article presents the supporting claims for transplantation as well as aspects related to the mobilization regime, conditioning and perspectives of cell therapy.展开更多
Crohn's disease(CD)is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract.The etiology of CD is unknown;however,genetic,epigenetic,environmental,and lifestyle factors could ...Crohn's disease(CD)is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract.The etiology of CD is unknown;however,genetic,epigenetic,environmental,and lifestyle factors could play an essential role in the onset and establishment of the disease.CD results from immune dysregulation due to loss of the healthy symbiotic relationship between host and intestinal flora and or its antigens.It affects both sexes equally with a male to female ratio of 1.0,and its onset can occur at any age,but the diagnosis is most commonly observed in the range of 20 to 40 years of age.CD diminishes quality of life,interferes with social activities,traumatizes due to the stigma of incontinence,fistulae,strictures,and colostomies,and in severe cases,affects survival when compared to the general population.Symptoms fluctuate between periods of remission and activity in which complications such as fistulas,strictures,and the need for bowel resection,surgery,and colostomy implantation make up the most severe aspects of the disease.CD can be progressive and the complications recurrent despite treatment with anti-inflammatory drugs,corticosteroids,immunosuppressants,and biological agents.However,over time many patients become refractory without treatment alternatives,and in this scenario,hematopoietic stem cell transplantation(HSCT)has emerged as a potential treatment option.The rationale for the use of HSCT for CD is anchored in animal studies and human clinical trials where HSCT could reset a patient's immune system by eliminating disease-causing effector cells and upon immune recovery increase regulatory and suppressive immune cells.Autologous HSCT using a non-myeloablative regimen of cyclophosphamide and anti-thymocyte globulin without CD34+selection has been to date the most common transplant conditioning regimen adopted.In this review we will address the current situation regarding CD treatment with HSCT and emphasize the medical,ethical,and legal aspects that permeate the procedure in Brazil.展开更多
As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements...As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.展开更多
BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ru...BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.展开更多
急性移植物抗宿主病(acute graft versus host disease,aGVHD)是异基因造血干细胞移植后常见并发症,是目前导致造血干细胞移植后患者死亡的主要原因。以往的治疗策略主要依靠患者的临床症状及活组织病理检查,一旦患者被诊断为aGVHD,首...急性移植物抗宿主病(acute graft versus host disease,aGVHD)是异基因造血干细胞移植后常见并发症,是目前导致造血干细胞移植后患者死亡的主要原因。以往的治疗策略主要依靠患者的临床症状及活组织病理检查,一旦患者被诊断为aGVHD,首选给予类固醇类激素治疗。但是,若激素治疗效果不佳,则病人预后往往较差。近年来,随着相关领域研究的不断深入,aGVHD的治疗方案不断优化,本文主要就aGVHD的临床特征、发病机制及最新策略,包括单克隆抗体药物治疗、物理治疗和细胞治疗等作一综述。展开更多
文摘Hepatic veno-occlusive disease(VOD), also known as sinusoidal obstruction syndrome, is a major complication of hematopoietic stem cell transplantation and it carries a high mortality. Prophylaxis for hepatic VOD is commonly given to transplant recipients from the start of conditioning through the early weeks of transplant. However, high quality evidence from randomized controlled trials is scarce with small sample sizes and the trials yielded conflicting results. Although various treatment options for hepatic VOD are available, most have not undergone stringent evaluation with randomized controlled trial and therefore it remains uncertain which treatment offers real benefit. It remains controversial whether VOD prophylaxis should be given, which prophylactic therapy should be given, who should receive prophylaxis, and what treatment should be offered once VOD is established.
文摘Background: The unavoidable links between the benefits of conventional systemic treatment of cancer and the side effects such as lymphopenia. Objective: To analyze this phenomenon in view of the newly discovered trophic function of circulating hematopoietic stem cells (HSC) and their lymphocyte descendants. Method: We used population statistics and recent current research involving natural aging and preliminary aging with cancer, its cytotoxic therapy, eclampsia at pregnancy, and radiation hormesis. Results: In contrast to immune-defense interpretations of these health conditions, the trophic influence of HSC and morphogenic lymphocytes on natural tissue renewal and regeneration after sublethal injuries eliminates the majority of covered inconsistencies, which are inherent to the dominating idea of cellular immunity. Conclusion: Our examination led to the feeding influence of lymphopoiesis on tumor progression, an indirect mechanism of tumor growth control by systemic therapy via either destruction of trophic cells, or by competitive distraction from malignant tissue via reparation of sublethal injuries in normal tissues. Analyses also involved similarities of the mechanisms of systemic chemotherapy and total body/half body radiotherapy in low doses, as well as the futility of the theoretical opposition of the radiation hormesis phenomenon to the linear non-threshold model, dominant in radiobiology.
文摘Summary:It has been identified that malnutrition can influence the immune system and time of engraftment,and it's also associated with increased incidence of complications,prolonged length of hospital stays,and transplant mortality and morbidity in patients undergoing hematopoietic stem cell transplantation(HSCT),so dynamic nutrition care is highly important.The aim of this study was to better understand the differences between clinical nutrition practices and international recommendations as well as possible barriers to the use of nutrition support in HSCT patients.An evidence-based nutrition support pathway was constructed through a systematic literature review to identify evidence and recommendations relating to the relevant issues.Then,a questionnaire consisting of 28 questions that focused on the 4 topics,namely,assessment and screening for malnutrition,nutrition support interventions,nutrition support in gastrointestinal graft-ver5U5・host disease(GVHD)and neutropenic diet was developed by the study authors and used for data collection.Responses of 18 HSCT centers from 17 provinces were received.General assessment for malnutrition was performed at 72%(13/18)centers.Parenteral nutrition(PN)was given as the first option to HSCT patients in the majority of centers,despite the fact that current guidelines recommend enteral nutrition(EN)over PN.As many as 72%(13/18)of the centers considered a neutropenic diet in the management of HSCT patients,but only one center had a formal neutropenic diet protocol in place for transplant recipients.Criteria for initiating nutrition support in patients with gastrointestinal GVHD were heterogeneous among the centers,and PN was the most widely used technique.The survey results revealed significant heterogeneity with regard to nutrition support practices among the centers,as well as between the practices and the guidelines.Standard nutrition support guidelines or protocols for nutrition support practices were absent in most of the centers.
文摘Crohn's disease(CD) is an inflammatory bowel disease that can affect any site of the digestive system. It occurs due to an immunological imbalance and is responsible for intestinal mucosal lesions and complications such as fistulas and stenoses. Treatment aims to stabilize the disease, reducing the symptoms and healing intestinal lesions. Surgical procedures are common in patients. Cell therapy was initially used to treat this disease in patients who also suffered from lymphoma and leukemia and were considered to be good candidates for autologous and allogeneic transplantation. After transplantation, an improvement was also observed in their CD. In 2003, the procedure began to be used to treat the disease itself, and several case series and randomized studies have been published since then; this approach currently comprises a new option in the treatment of CD. However, considerable doubt along with significant gaps in our knowledge continue to exist in relation to cell therapy for CD. Cell therapy is currently restricted to the autologous modality of hematopoietic stem cell transplantation and, experimentally, to mesenchymal stromal cells to directly treat lesions of the anal mucosa. This article presents the supporting claims for transplantation as well as aspects related to the mobilization regime, conditioning and perspectives of cell therapy.
文摘Crohn's disease(CD)is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract.The etiology of CD is unknown;however,genetic,epigenetic,environmental,and lifestyle factors could play an essential role in the onset and establishment of the disease.CD results from immune dysregulation due to loss of the healthy symbiotic relationship between host and intestinal flora and or its antigens.It affects both sexes equally with a male to female ratio of 1.0,and its onset can occur at any age,but the diagnosis is most commonly observed in the range of 20 to 40 years of age.CD diminishes quality of life,interferes with social activities,traumatizes due to the stigma of incontinence,fistulae,strictures,and colostomies,and in severe cases,affects survival when compared to the general population.Symptoms fluctuate between periods of remission and activity in which complications such as fistulas,strictures,and the need for bowel resection,surgery,and colostomy implantation make up the most severe aspects of the disease.CD can be progressive and the complications recurrent despite treatment with anti-inflammatory drugs,corticosteroids,immunosuppressants,and biological agents.However,over time many patients become refractory without treatment alternatives,and in this scenario,hematopoietic stem cell transplantation(HSCT)has emerged as a potential treatment option.The rationale for the use of HSCT for CD is anchored in animal studies and human clinical trials where HSCT could reset a patient's immune system by eliminating disease-causing effector cells and upon immune recovery increase regulatory and suppressive immune cells.Autologous HSCT using a non-myeloablative regimen of cyclophosphamide and anti-thymocyte globulin without CD34+selection has been to date the most common transplant conditioning regimen adopted.In this review we will address the current situation regarding CD treatment with HSCT and emphasize the medical,ethical,and legal aspects that permeate the procedure in Brazil.
基金Supported by the Scientific Research Project of the Sichuan Province Education Department,No. 16ZA0241the National Natural Science Foundation of China,No. 82060268the Guangxi Natural Science Foundation of China,No. 2020JJA140124。
文摘As an important treatment for acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation(allo-HSCT) plays an important role in reducing relapse and improving long-term survival. With rapid advancements in basic research in molecular biology and immunology and with deepening understanding of the biological characteristics of hematopoietic stem cells, allo-HSCT has been widely applied in clinical practice. During allo-HSCT, preconditioning, the donor, and the source of stem cells can be tailored to the patient’s conditions, greatly broadening the indications for HSCT, with clear survival benefits. However, the risks associated with allo-HSCT remain high, i.e. hematopoietic reconstitution failure, delayed immune reconstitution, graft-versus-host disease, and posttransplant relapse, which are bottlenecks for further improvements in allo-HSCT efficacy and have become hot topics in the field of HSCT. Other bottlenecks recognized in the current treatment of individuals diagnosed with acute myeloid leukemia and subjected to allo-HSCT include the selection of the most appropriate conditioning regimen and post-transplantation management. In this paper, we reviewed the progress of relevant research regarding these aspects.
文摘BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.
文摘急性移植物抗宿主病(acute graft versus host disease,aGVHD)是异基因造血干细胞移植后常见并发症,是目前导致造血干细胞移植后患者死亡的主要原因。以往的治疗策略主要依靠患者的临床症状及活组织病理检查,一旦患者被诊断为aGVHD,首选给予类固醇类激素治疗。但是,若激素治疗效果不佳,则病人预后往往较差。近年来,随着相关领域研究的不断深入,aGVHD的治疗方案不断优化,本文主要就aGVHD的临床特征、发病机制及最新策略,包括单克隆抗体药物治疗、物理治疗和细胞治疗等作一综述。
