Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cel...Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation(HSCT).Methods: A total of 108 patients with various hematological disorders were selected from Peking University People’s Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.Results: After HSCT, significant decreases in calf circumference and body mass index(BMI) were observed,accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT(P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients(P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the postHSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre-and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size(LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups(P<0.05).Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.展开更多
Objective: To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation(HSCT), and explore optimal methods for assessing nutritional status in patients with hematologic...Objective: To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation(HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases.Methods: This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002(NRS-2002), Mini Nutritional Assessment(MNA), Subjective Global Assessment(SGA) and Malnutrition Universal Screening Tools(MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms.Results: After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk,compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT,compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT.Conclusions: Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.展开更多
Both,autologous and allogeneic hematopoietic stem cell transplantation(HSCT)can be used to cure or ameliorate a variety of malignant and non-malignant diseases.The rationale behind this strategy is based on the concep...Both,autologous and allogeneic hematopoietic stem cell transplantation(HSCT)can be used to cure or ameliorate a variety of malignant and non-malignant diseases.The rationale behind this strategy is based on the concept of immunoablation using high-dose chemotherapy,with subsequent regeneration of naive T-lymphocytes derived from reinfused hematopoietic progenitor cells.In addition,the use of HSCT allows for the administration of high-dose chemotherapy(whether or not combined with immunomodulating agents such as antithymocyte globulin)resulting in a prompt remission in therapy-refractory patients.This review gives an update of the major areas of successful uses of HSCT in non-malignant gastrointestinal disorders.A Medline search has been conducted and all relevant published data were analyzed.HSCT has been proved successful in treating refractory Crohn’s disease(CD).Patientswith refractory celiac disease typeⅡand a high risk of developing enteropathy associated T-cell lymphoma have shown promising improvement.Data concerning HSCT and mesenchymal SCT in end-stage chronic liver diseases are encouraging.In refractory autoimmune gastrointestinal diseases high-dose chemotherapy followed by HSCT seems feasible and safe and might result in long-term improvement of disease activity.Mesenchymal SCT for a selected group of CD is promising and may represent a significant therapeutic alternative in treating fistulas in CD.展开更多
Hematopoietic stem cell transplant(HSCT) is a standard treatment for many hematological malignancies.Three different sources of stem cells, namely bone marrow(BM), peripheral blood stem cells(PBSC) and cord blood(CB) ...Hematopoietic stem cell transplant(HSCT) is a standard treatment for many hematological malignancies.Three different sources of stem cells, namely bone marrow(BM), peripheral blood stem cells(PBSC) and cord blood(CB) can be used for HSCT, and each has its own advantages and disadvantages. Randomized controlled trials(RCTs) suggest that there is no significant survival advantage of PBSC over BM in Human Leukocyte Antigen-matched sibling transplant for adult patients with hematological malignancies. PBSC transplant probably results in lower risk of relapse and hence better disease-free survival, especially in patients with high risk disease at the expense of higher risks of both severe acute and chronic graft-versus-host disease(GVHD).In the unrelated donor setting, the only RCT available suggests that PBSC and BM result in comparable overall and disease-free survivals in patients with hematological malignancies; and PBSC transplant results in lower risk of graft failure and higher risk of chronic GVHD.High level evidence is not available for CB in comparison to BM or PBSC. The risks and benefits of different sources of stem cells likely change with different conditioning regimen, strategies for prophylaxis and treatment of GVHD and manipulation of grafts. The recent success and rapid advance of double CB transplant and haploidentical BM and PBSC transplants further complicate the selection of stem cell source. Optimal selection requires careful weighing of the risks and benefits of different stem cell source for each individual recipient and donor. Detailed counseling of patient and donor regarding risks and benefits in the specific context of the patient and transplant method is essential for informed decision making.展开更多
Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of do...Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatmentrelated toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental preclinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase Ⅱ trials that will be summarized in this review.展开更多
Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35...Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35 patients P 】 50 years with malignant hematological diseases received allogeneic hematopoietic展开更多
While much progress has been made in the field of hematopoietic stem cell transplantation (HSCT), headway in the promotion of recovery following this procedure has been limited. Data regarding the potential of Chine...While much progress has been made in the field of hematopoietic stem cell transplantation (HSCT), headway in the promotion of recovery following this procedure has been limited. Data regarding the potential of Chinese herbal medicine (CHM) for patients with hematologic disorders who received HSCT are gradually increasing; however, these data are mostly in Chinese. Therefore, we set out to summarize the existing data. We searched PubMed, the Cochrane Library and the China National Knowledge Infrastructure and retrieved 9 clinical studies related to this group of patients, in whom CHM was used as an intervention. Of the 9 papers, 6 were published by the same group of researchers. The focus of the reviewed studies was heterogeneous, and the objectives varied widely. With the exception of one randomized control trial, all of the studies were retrospective and observational; the median number of patients was 11.5, with the largest study containing 104 patients. CHM treatment was largely divided into two stages: (1) pre-HSCT, which was initiated as soon as conditioning chemotherapy was administered and aimed to counterbalance the adverse effects of these potent agents; (2) post-HSCT, which began immediately after transplantation and was intended to promote engraftment, control graft- versus-host disease and prolong survival. In addition, the 9 Chinese materia medica most commonly prescribed (appearing in four studies) were: Shengdihuang (Rehmannia glutinosa), Baizhu (Atractylodes macrocephala), Renshen (Panax ginseng), Dangshen ( Codonopsis pilosula), Maimendong ( Ophiopogon japonicus), Danggui (Angelica sinensis), Taizishen (Pseudostellaria heterophylla), Huangqi (Astragalus membranaceus) and Ejiao (Equus asinus).展开更多
Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic ...Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic malignancies.Methods The protocol was designed to minimize the intensity of the conditioning regimen to the range of nonmyeloablative therapies based on ATG with low-dose busulfan (Bu) and Cytoxan (CTX) (15-19.5 mg/kg, 8 mg/kg and 80 mg/kg, respectively). The patients received the first lymphocytic infusion from HLA-identical sibling donors on days 28-30 after transplant, and the first T cell dosage of 10 6/kg followed by the escalated dosage in the range of (0.5-1.5)×10 8/kg. The total number of procedures were performed at a median of 4.2 procedures (range of 2-8 procedures).Results Engraftment was documented in all six patients in the form of donor-recipient hematopoietic cells mixed chimera at early-stage posttransplant, which was converted gradually into complet chimera by DLI in four patients. Graft-versus-host disease (GVHD) developed in three of six cases, only one of which was severe. To date,four patients are disease free and alive.Conclusions Allogeneic donor stem cell engraftment into host can be achieved by nonmyeloablative conditioning regimen based on ATG. Transient mixed donor-recipient hematopoietic cell mixed with chimeras may be successfully converted into complete chimerism by DLI posttransplant. GVHD remains major clinical concern in our study.展开更多
Rituximab is a mouse and human chimeric CD<sub>20</sub> (anti-B cell) specific monoclonal antibody that has been approved by the U.S. Food and Drug Administration for the treatment of lymphoma. The express...Rituximab is a mouse and human chimeric CD<sub>20</sub> (anti-B cell) specific monoclonal antibody that has been approved by the U.S. Food and Drug Administration for the treatment of lymphoma. The expression of CD<sub>20</sub> antigen is expressed in the whole ontogeny of B cells, starting from the premature B cells in bone marrow to the differentiation of plasma cells in secondary lymphoid tissues. The wide distribution of CD<sub>20</sub> molecules allows rituximab to eliminate a large number of B cells. Rituximab is the core drug for the treatment of hematological diseases, often combined with drugs as a first-line treatment. Long-term hormone therapy often results in serious adverse reactions, and new therapies, which can avoid widespread immunotoxicity, have great potential for treating diseases of the blood system.展开更多
BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation...BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation of GVHD in post-HSCT patients with differing GI symptoms.Further,the diagnostic value of gross endoscopic findings as well as the safety of endoscopy in this commonly thrombocytopenic and neutropenic patient population remains unclear.AIM To understand the diagnostic value of symptoms and gross endoscopic findings as well as safety of endoscopy in aGVHD patients.METHODS We analyzed 195 endoscopies performed at City of Hope in patients who underwent allogeneic HSCT less than 100 d prior for hematologic malignancy and were subsequently evaluated for aGVHD via endoscopy.The yield,sensitivity,and specificity of diagnosing aGVHD were calculated for upper and lower endoscopy,various GI tract locations,and presenting symptoms.RESULTS Combined esophagogastroduodenoscopy(EGD)and flexible sigmoidoscopy(FS)demonstrated a greater diagnostic yield for aGVHD(83.1%)compared to EGD(66.7%)or FS(77.2%)alone with any presenting symptom.The upper and lower GI tract demonstrated similar yields regardless of whether patients presented with diarrhea(95.7%vs 99.1%)or nausea/vomiting(97.5%vs 96.8%).Normalappearing mucosa was generally as specific(91.3%)as abnormal mucosa(58.7%-97.8%)for the presence of aGVHD.Adverse events such as bleeding(1.0%),infection(1.0%),and perforation(0.5%)only occurred in a small proportion of patients,with no significant differences in those with underlying thrombocytopenia(P=1.000)and neutropenia(P=0.425).CONCLUSION Combined EGD and FS with biopsies of normal and inflamed mucosa demonstrated the greatest diagnostic yield regardless of presenting symptom and appears to be safe in this population of patients.展开更多
Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabc...Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.展开更多
Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Wi...Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Without a suitable related or unrelated HLA-matched donor,umbilical cord blood and haploidentical family members provide a potential source of stem cells. Timely donor availability makes haploidentical donors an attractive alternative donor source. Initial attempts at haploidentical HSCT was associated with significantly increased mortality owing to high rates of graft rejection and severe graftversus-host disease caused by major donor-recipient HLAdisparity. However, over the past decade, outcomes of haploidentical HSCT have improved significantly. Here, we review the advantages and challenges of haploidentical transplantation. We also discuss new developments to attempt to overcome the challenges to a successful haploidentical transplantation.展开更多
基金supported by Grant National Key R&D Program of China (No.2020YFC2005600 and No.2020YFC2005605)。
文摘Objective: The aim of this study was to investigate the prevalence of sarcopenia(SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation(HSCT).Methods: A total of 108 patients with various hematological disorders were selected from Peking University People’s Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity.Results: After HSCT, significant decreases in calf circumference and body mass index(BMI) were observed,accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT(P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients(P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the postHSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre-and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size(LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups(P<0.05).Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.
文摘Objective: To investigate the nutritional status of patients before and after hematopoietic stem cell transplantation(HSCT), and explore optimal methods for assessing nutritional status in patients with hematological diseases.Methods: This cohort study enrolled 170 patients who were diagnosed with hematological diseases and underwent allogeneic HSCT in the Department of Hematology, Peking University People's Hospital between May2011 and April 2013. We used fixed-point continuous sampling and four nutritional screening tools, Nutritional Risk Screening 2002(NRS-2002), Mini Nutritional Assessment(MNA), Subjective Global Assessment(SGA) and Malnutrition Universal Screening Tools(MUST), in combination with body measurements, to extensively screen and evaluate nutritional risks and status in patients receiving HSCT before entering and after leaving laminar air flow rooms.Results: After HSCT, patients had significant reduction in weight, hip circumference, waist-hip ratio, calf circumference, mid-upper arm circumference, and suprailiac skinfold thickness compared with pre-HSCT measurements. Before HSCT, NRS-2002 identified that 21.2% of patients were at nutritional risks, compared with100% after HSCT. MUST indicated that before HSCT, 11.77% of patients were at high nutritional risk,compared with 59.63% after HSCT. MNA assessed that 0.06% of patients were malnourished before HSCT,compared with 19.27% after HSCT. SGA identified that before HSCT, 1.76% of patients had mild to severe malnutrition, which increased to 83.3% after HSCT. There is a significant increase in the nutritional risk and malnutrition in patients who received HSCT.Conclusions: Before HSCT, some patients already had nutritional risk or nutritional deficiencies, and prompt and close nutritional screening or assessment should be performed. The nutritional status of patients after HSCT was generally deteriorated compared with that before transplantation. Body measurements should be taken more frequently during the subsequent treatment window in the laminar air flow rooms. After HSCT, it is recommended to combine MNA and SGA to fully evaluate the nutritional status, and thus provide timely and reasonable nutritional support.
文摘Both,autologous and allogeneic hematopoietic stem cell transplantation(HSCT)can be used to cure or ameliorate a variety of malignant and non-malignant diseases.The rationale behind this strategy is based on the concept of immunoablation using high-dose chemotherapy,with subsequent regeneration of naive T-lymphocytes derived from reinfused hematopoietic progenitor cells.In addition,the use of HSCT allows for the administration of high-dose chemotherapy(whether or not combined with immunomodulating agents such as antithymocyte globulin)resulting in a prompt remission in therapy-refractory patients.This review gives an update of the major areas of successful uses of HSCT in non-malignant gastrointestinal disorders.A Medline search has been conducted and all relevant published data were analyzed.HSCT has been proved successful in treating refractory Crohn’s disease(CD).Patientswith refractory celiac disease typeⅡand a high risk of developing enteropathy associated T-cell lymphoma have shown promising improvement.Data concerning HSCT and mesenchymal SCT in end-stage chronic liver diseases are encouraging.In refractory autoimmune gastrointestinal diseases high-dose chemotherapy followed by HSCT seems feasible and safe and might result in long-term improvement of disease activity.Mesenchymal SCT for a selected group of CD is promising and may represent a significant therapeutic alternative in treating fistulas in CD.
文摘Hematopoietic stem cell transplant(HSCT) is a standard treatment for many hematological malignancies.Three different sources of stem cells, namely bone marrow(BM), peripheral blood stem cells(PBSC) and cord blood(CB) can be used for HSCT, and each has its own advantages and disadvantages. Randomized controlled trials(RCTs) suggest that there is no significant survival advantage of PBSC over BM in Human Leukocyte Antigen-matched sibling transplant for adult patients with hematological malignancies. PBSC transplant probably results in lower risk of relapse and hence better disease-free survival, especially in patients with high risk disease at the expense of higher risks of both severe acute and chronic graft-versus-host disease(GVHD).In the unrelated donor setting, the only RCT available suggests that PBSC and BM result in comparable overall and disease-free survivals in patients with hematological malignancies; and PBSC transplant results in lower risk of graft failure and higher risk of chronic GVHD.High level evidence is not available for CB in comparison to BM or PBSC. The risks and benefits of different sources of stem cells likely change with different conditioning regimen, strategies for prophylaxis and treatment of GVHD and manipulation of grafts. The recent success and rapid advance of double CB transplant and haploidentical BM and PBSC transplants further complicate the selection of stem cell source. Optimal selection requires careful weighing of the risks and benefits of different stem cell source for each individual recipient and donor. Detailed counseling of patient and donor regarding risks and benefits in the specific context of the patient and transplant method is essential for informed decision making.
文摘Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is fully haplotype mismatched. Previously this procedure was limited by graft rejection, lethal graft-versus-host disease, and increased treatmentrelated toxicity. Recent approaches in haplo-identical transplantation have demonstrated significantly improved outcomes. Based on years of incremental preclinical research into this unique form of bone marrow transplant, a range of approaches have now been studied in patients in relatively large phase Ⅱ trials that will be summarized in this review.
文摘Objective To investigate the efficiency and safety of allogeneic hematopoietic cell transplantation for malignant hematological diseases in patients older than 50 years of age. Methods From May 2002 to January 2010,35 patients P 】 50 years with malignant hematological diseases received allogeneic hematopoietic
基金supported by a grant from the China Medical University Hospital(DMR-105-005)
文摘While much progress has been made in the field of hematopoietic stem cell transplantation (HSCT), headway in the promotion of recovery following this procedure has been limited. Data regarding the potential of Chinese herbal medicine (CHM) for patients with hematologic disorders who received HSCT are gradually increasing; however, these data are mostly in Chinese. Therefore, we set out to summarize the existing data. We searched PubMed, the Cochrane Library and the China National Knowledge Infrastructure and retrieved 9 clinical studies related to this group of patients, in whom CHM was used as an intervention. Of the 9 papers, 6 were published by the same group of researchers. The focus of the reviewed studies was heterogeneous, and the objectives varied widely. With the exception of one randomized control trial, all of the studies were retrospective and observational; the median number of patients was 11.5, with the largest study containing 104 patients. CHM treatment was largely divided into two stages: (1) pre-HSCT, which was initiated as soon as conditioning chemotherapy was administered and aimed to counterbalance the adverse effects of these potent agents; (2) post-HSCT, which began immediately after transplantation and was intended to promote engraftment, control graft- versus-host disease and prolong survival. In addition, the 9 Chinese materia medica most commonly prescribed (appearing in four studies) were: Shengdihuang (Rehmannia glutinosa), Baizhu (Atractylodes macrocephala), Renshen (Panax ginseng), Dangshen ( Codonopsis pilosula), Maimendong ( Ophiopogon japonicus), Danggui (Angelica sinensis), Taizishen (Pseudostellaria heterophylla), Huangqi (Astragalus membranaceus) and Ejiao (Equus asinus).
文摘Objective To evaluate the application of anti-T-lymphocyte globulin (ATG) based nonmyeloablative but profoundly immunosuppressive regimens followed by donor lymphocyte infusion (DLI) for the treatment of hematologic malignancies.Methods The protocol was designed to minimize the intensity of the conditioning regimen to the range of nonmyeloablative therapies based on ATG with low-dose busulfan (Bu) and Cytoxan (CTX) (15-19.5 mg/kg, 8 mg/kg and 80 mg/kg, respectively). The patients received the first lymphocytic infusion from HLA-identical sibling donors on days 28-30 after transplant, and the first T cell dosage of 10 6/kg followed by the escalated dosage in the range of (0.5-1.5)×10 8/kg. The total number of procedures were performed at a median of 4.2 procedures (range of 2-8 procedures).Results Engraftment was documented in all six patients in the form of donor-recipient hematopoietic cells mixed chimera at early-stage posttransplant, which was converted gradually into complet chimera by DLI in four patients. Graft-versus-host disease (GVHD) developed in three of six cases, only one of which was severe. To date,four patients are disease free and alive.Conclusions Allogeneic donor stem cell engraftment into host can be achieved by nonmyeloablative conditioning regimen based on ATG. Transient mixed donor-recipient hematopoietic cell mixed with chimeras may be successfully converted into complete chimerism by DLI posttransplant. GVHD remains major clinical concern in our study.
文摘Rituximab is a mouse and human chimeric CD<sub>20</sub> (anti-B cell) specific monoclonal antibody that has been approved by the U.S. Food and Drug Administration for the treatment of lymphoma. The expression of CD<sub>20</sub> antigen is expressed in the whole ontogeny of B cells, starting from the premature B cells in bone marrow to the differentiation of plasma cells in secondary lymphoid tissues. The wide distribution of CD<sub>20</sub> molecules allows rituximab to eliminate a large number of B cells. Rituximab is the core drug for the treatment of hematological diseases, often combined with drugs as a first-line treatment. Long-term hormone therapy often results in serious adverse reactions, and new therapies, which can avoid widespread immunotoxicity, have great potential for treating diseases of the blood system.
文摘BACKGROUND Acute gastrointestinal(GI)graft-vs-host disease(aGVHD)is the most complication of hematopoietic stem cell transplant(HSCT)in patients with hematologic malignancy.Limited data exists on endoscopic evaluation of GVHD in post-HSCT patients with differing GI symptoms.Further,the diagnostic value of gross endoscopic findings as well as the safety of endoscopy in this commonly thrombocytopenic and neutropenic patient population remains unclear.AIM To understand the diagnostic value of symptoms and gross endoscopic findings as well as safety of endoscopy in aGVHD patients.METHODS We analyzed 195 endoscopies performed at City of Hope in patients who underwent allogeneic HSCT less than 100 d prior for hematologic malignancy and were subsequently evaluated for aGVHD via endoscopy.The yield,sensitivity,and specificity of diagnosing aGVHD were calculated for upper and lower endoscopy,various GI tract locations,and presenting symptoms.RESULTS Combined esophagogastroduodenoscopy(EGD)and flexible sigmoidoscopy(FS)demonstrated a greater diagnostic yield for aGVHD(83.1%)compared to EGD(66.7%)or FS(77.2%)alone with any presenting symptom.The upper and lower GI tract demonstrated similar yields regardless of whether patients presented with diarrhea(95.7%vs 99.1%)or nausea/vomiting(97.5%vs 96.8%).Normalappearing mucosa was generally as specific(91.3%)as abnormal mucosa(58.7%-97.8%)for the presence of aGVHD.Adverse events such as bleeding(1.0%),infection(1.0%),and perforation(0.5%)only occurred in a small proportion of patients,with no significant differences in those with underlying thrombocytopenia(P=1.000)and neutropenia(P=0.425).CONCLUSION Combined EGD and FS with biopsies of normal and inflamed mucosa demonstrated the greatest diagnostic yield regardless of presenting symptom and appears to be safe in this population of patients.
文摘Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
文摘Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Without a suitable related or unrelated HLA-matched donor,umbilical cord blood and haploidentical family members provide a potential source of stem cells. Timely donor availability makes haploidentical donors an attractive alternative donor source. Initial attempts at haploidentical HSCT was associated with significantly increased mortality owing to high rates of graft rejection and severe graftversus-host disease caused by major donor-recipient HLAdisparity. However, over the past decade, outcomes of haploidentical HSCT have improved significantly. Here, we review the advantages and challenges of haploidentical transplantation. We also discuss new developments to attempt to overcome the challenges to a successful haploidentical transplantation.