COVID-19 impact in Crohn’s disease patients submitted to autologous hematopoietic stem cell transplantation

BACKGROUND Severe acute respiratory syndrome coronavirus 2 is the virus responsible for coronavirus disease 2019(COVID-19),a disease that has been blamed for inducing or exacerbating symptoms in patients with autoimmune diseases.Crohn's disease(CD)is an inflammatory bowel disease that affects genetically susceptible patients who develop an abnormal mucosal immune response to the intestinal microbiota.Patients who underwent hematopoietic stem cell transplantation(HSCT)are considered at risk for COVID-19.AIM To describe for the first time the impact of COVID-19 in CD patients who had undergone autologous,non-myeloablative HSCT.METHODS In this descriptive study a series of 19 patients were diagnosed with positive COVID-19.For two patients there were reports of the occurrence of two infectious episodes.Parameters related to HSCT,such as time elapsed since the procedure,vaccination status,CD status before and after infection,and clinical manifestations resulting from COVID-19,were evaluated.RESULTS Among the patients with COVID-19,three,who underwent Auto HSCT less than six months ago,relapsed and one,in addition to the CD symptoms,started to present thyroid impairment with positive anti-TPO.Only one of the patients required hospitalization for five days to treat COVID-19 and remained in CD clinical remission.Nine patients reported late symptoms that may be related to COVID-19.There were no deaths,and a statistical evaluation of the series of COVID-19 patients compared to those who did not present any infectious episode did not identify significant differences regarding the analyzed parameters.CONCLUSION Despite the change in CD status in three patients and the presence of nine patients with late symptoms,we can conclude that there was no significant adverse impact concerning COVID-19 in the evaluated patients who underwent HSCT to treat CD.

Sarcopenia and gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation

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.

Hematopoietic stem cell transplantation of aplastic anemia by relative with mutations and normal telomere length: A case report

BACKGROUND Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation(MSD-HSCT)are the preferred treatments for aplastic anemia(AA).CASE SUMMARY In this report,we describe a 43-year-old male patient with severe AA who carried BRIP1(also known as FANCJ),TINF2,and TCIRG1 mutations.Screening of the family pedigree revealed the same TINF2 mutation in his mother and older brother,with his older brother also carrying the BRIP1 variant and demonstrating normal telomere length and hematopoietic function.The patient was successfully treated with oral cyclosporine A,eltrombopag,and acetylcysteine,achieving remission 4 years after receiving MSD-HSCT from his older brother.CONCLUSION This case provides a valuable clinical reference for individuals with suspected pathogenic gene mutations,normal telomere length,and hematopoietic function,highlighting them as potential donors for patients with AA.

Advantageous tactics with certain probiotics for the treatment of graft-versus-host-disease after hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.

Umbilical Cord Blood-derived Mesenchymal Stem Cells Ameliorate Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation through Multiple Immunoregulations

Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs （UCB-hMSCs） on GVHD patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells （DCs） and cytokines including interleukin-17 （IL-17） and tumor necrosis factor-alpha （TNF-α） were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^＋, CD3＋CD4^＋ and CD3＋CD8^＋ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^＋ and CD8^＋ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.

Allogeneic stem cell transplantation in the treatment of acute myeloid leukemia: An overview of obstacles and opportunities

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.

Comprehensive evaluation of nutritional status before and after hematopoietic stem cell transplantation in 170 patients with hematological diseases

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.

Autologous hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: treatment outcome and prognostic factor analysis

Objective： The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation （AHSCT） in the treatment of lymphoblastic lymphoma （LL）. Methods： We relxospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation （HSCT） from December 1989 to December 2009 in a single institution. Results： HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months （range, 24.6-173.1 months）. The 5-year overall survival （OS） and event-free survival （EFS） rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow （BM） involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis. Conclusions These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission （CR1）.

Decitabine for Relapsed Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Relapse after allogeneic hematopoietic stem cell transplantation（allo-HSCT） remains a main question on treatment failure. Current strategies for management that usually include salvage chemotherapy, donor lymphocytic infusion and second transplantation. Our study assessed the efficacy of decitabine（DAC） for treating patients with acute lymphoblastic leukemia（ALL） who relapsed after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. We retrospectively analyzed the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC therapy. Nine patients received DAC combined with chemotherapy and donor stem cell infusion, and 3 patients received single-agent DAC. Ten of the 12 patients achieved complete remission（CR）, 1 achieved a partial remission（PR）, and 1 had no response（NR） after treatment at the latest follow-up（LFU）, the median survival was 11.2 months（range, 3.8–34, 7 months）. The 1-and 2-year overall survival（OS） rates were 50%（6/12） and 25%（3/12）, respectively. Five patients were still alive; 4 had maintained CR and 1 was alive with disease. Patients with Philadelphia chromosome-positive ALL had higher survival rate than patients with Philadelphia chromosome-negative ALL（57.1% vs. 20%）. No aggravated flares of graft-versus-host disease（GVHD） were observed during DAC treatment. Therefore, DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.

Clinical Observation of Patients with Hematologic Malignancies Treated with Hematopoietic Stem Cell Transplantation

To evaluate the therapeutic effect of hematopoietic stem cell transplantation (HSCT), we performed HSCT in 30 patients with hematologic maligancies. Of the 30 patients, 10 underwent autologous peripheral blood stem cell transplantation (auto-PBSCT), 13 underwent myeloablative allogeneic HSCT while 7 underwent nonmyeloablative allogeneic HSCT, which were designated as autologous group, myeloablative group and nonmyeloablative group, respectively. All patients except the one who underwent cord blood transplantation, were successfully engrafted. Median time for the granulocytes≥0.5×10\+9/L and platelets≥20×10\+9/L were 12 days and 13 days respectively in autologous group, 16 days and 19 days in myeloablative group, 15 days and 12 days in nonmyeloablative group. In myeloablative group, acute graft-versus-host diseases (aGVHD) was observed in 3 patients, all of which were I—Ⅱgrade. Oral mucous cGVHD was observed in 1 patient. In nonmyeloablative group, 1 patient developed intestinal aGVHD grade Ⅳ and cutaneous cGVHD was induced by donor lymphocyte infusions (DLI) in 3 patients. 1 patient had hematological relapse in autologous group. 1 patient had cytogenetic relapse in myeloablative group. In nonmyeloablative group 3 patients had cytogenetic relapse and were cured by DLI, 1 patient had hematological relapse. 4 of the 30 patients died of infection (2 patients), grade Ⅳ aGVHD (1) and relapse (1) respectively. 26 patients are still alive. 3 years overall survival (OS) and 3 years disease free survival (DFS) were 100 % and 64.81 % respectively in autologous group, 78.75 % and 63 % respectively in myeloablative group while both 66.67 % in nonmyeloablative group. In conclusion, autologous group had less transplant-related complications and mortality. Active prophylaxis of relapse could significantly promote DFS. The transplant-related mortality limited DFS in myeloablative group. More relapses occurred in nonmyeloablative group, but could be cured by DLI.

Gut microbiome in allogeneic hematopoietic stem cell transplantation and specific changes associated with acute graft vs host disease

Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.

High-dose Chemotherapy Combined with Autologous Hematopoietic Stem Cell Transplantation as Frontline Therapy for Intermediate/High-risk Diffuse Large B Cell Lymphoma

The role of autologous hematopoietic stem cell transplantation(auto-HSCT)following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphoma(DLBCL).However,its clinical efficacy as frontline therapy remains to be elucidated.This study aimed to examine the feasibility of frontline auto-HSCT for newly diagnosed intermediate/high-risk DLBCL patients.We retrospectively reviewed the data of 223 patients treated with frontline auto-HSCT or chemotherapy alone(year 2008-2014)from four hospitals.The median follow-up time was 29.4 months.Between the two treatment arms among the intermediate/high-risk DLBCL patients,the 3-year overall survival(OS)and progression-free survival(PFS)rates of patients given frontline auto-HSCT were 87.6%and 81.9%,respectively,and the chemotherapy-alone group showed 3-year OS and PFS rates of 64.9%and 59.59%,respectively.Compared with the chemotherapy-alone group,the frontline auto-HSCT could eliminate the adverse impact of non-germinal center B-cell(GCB)type.In addition,in the frontline auto-HSCT group,patients who achieved complete response(CR)at auto-HSCT had a longer survival time than those who did not achieve CR.Our results suggested that frontline auto-HSCT could improve the prognosis of intennediate/high-risk DLBCL patients.

Medical,ethical,and legal aspects of hematopoietic stem cell transplantation for Crohn’s disease in Brazil

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.

Hematopoietic stem cell transplantation for Crohn's disease: Gaps, doubts and perspectives

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.

Allogeneic hematopoietic stem cell transplantation for patients with acute leukemia

Objective： The purposes of this study were to assess the efficacy of allogeneic hematopoietic stem cell transplantation （HSCT） for acute leukemia （AL） and analyze the factors affecting the prognosis of these patients. Methods： The clinical and follow-up data of 93 AL patients （median age, 30 years） undergoing allogeneic HSCT in Xiangya Hospital over the past 12 years were collected, and the potential factors affecting the efficacy and prognosis of allogeneic HSCT patients were determined. Results： Hematopoietic reconstitution was achieved in 90 patients. At the last follow-up, the incidences of severe acute graft versus host disease （aGvHD） and extensive chronic GvHD （cGvHD） were 14.0% and 20.0%, the 3-year cumulative incidence of transplantation related mortality （TRM） and relapse rate were 16.8%±6.1% and 21.3%±6.7%, and the estimated 3-year overall survival （OS） and disease-free survival （DFS） of the patients were 64.6%±5.4% and 56.5%±5.5%, respectively. Univariate analysis indicated that age older than 40 years, HLA mismatch, and severe lung infection within the first 100 days after transplantation were risk factors for severe aGvHD, age older than 40 years, HLA mismatch, severe lung infection within the first 100 days after transplantation, and severe aGvHD were risk factors for TRM, high-risk AL and lack of cGvHD were risk factors for relapse （all P〈0.05）. Survival estimation showed that HLA mismatch, severe lung infection occurring within the first 100 days post-transplantation, high-risk AL severe aGvHD and lack of cGvHD were risk factors associated with poor prognosis （all P〈0.05）. Further multivariate analyses revealed that severe lung infection within the first 100 days post-transplantation, severe aGvHD and lack of cGvHD were independent risk factors for unfavorable outcomes （all P〈0.05）. Conclusions： Allogeneic HSCT can improve the DFS of AL patients, and severe lung infection within the first 100 days post-transplantation, severe aGvHD and lack of cGvHD are independent risk factors affecting the prognosis.

Nutrition Support Practices of Hematopoietic Stem Cell Transplantation Centers in China's Mainland

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.

Psychosocial aspects of hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation(HSCT)has become a conventional and potentially curative treatment for various hematological diseases.As more sophisticated procedures have been developed and mortality rates have decreased,attention has shifted to the psychosocial challenges associated with transplantation.The psychosocial difficulties accompanying transplantation are addressed in the context of both quality of life(QOL)and psychopathological research.Among the psychiatric comorbidities of HSCT,anxiety,depression,sleep and sexual disorders,delirium and post-traumatic stress disorder are the most studied conditions.Recently,more attention has been focused on the psychosocial burden of caregivers.Devising recommendations for the management of psychiatric symptoms and psychosocial interventions in HSCT sufferers and close relatives is a major concern to consultation–liaison psychiatrists and transplant teams.This review synthesizes and critically evaluates the current literature on the psychosocial aspects of HSCT and appraises the clinical significance of these outcomes.Issues of QOL assessment;psychosocial functioning and QOL in the course of HSCT;impact of graft-versus-host disease and other predictors of QOL and psychosocial functioning;comorbid psychiatric disorders;and interventions to maintain or improve QOL and reduce psychopathology and psychosocial burden on family members are presented.

Endoscopic diagnosis of cytomegalovirus gastritis after allogeneic hematopoietic stem cell transplantation

AIM:To clarify the endoscopic and clinical findings of cytomegalovirus(CMV) gastritis after allogeneic hematopoietic stem cell transplantation(allo-SCT).METHODS:Between 1999 and 2005,523 patients underwent allo-SCT at our hospital,and 115 of these patients with gastrointestinal symptoms underwent esophagogastroduodenoscopy.RESULTS:CMV gastritis was diagnosed pathologically in seven patients(1.3%) with the other 108 patients serving as controls.Six of the seven patients developed positive CMV antigenemia,and five complained of abdominal pain.Development of abdominal pain preceded CMV antigenemia in four of the f ive patients.Endoscopic examination showed oozing(n=2),erosion(n=6),and redness(n=5) in the seven patients with CMV gastritis,while the control patients showed oozing(n=3),erosion(n=24),and redness(n=100).Erosion and oozing were more frequently documented in patients with CMV gastritis compared with the controls,and the differences were statistically significant(P=0.0012 and 0.029,respectively).CMV inclusion bodies were documented in 12 of 14 biopsy specimens obtained from erosive lesions,while they were identif ied in 4 of 15 biopsy specimens obtained from lesions other than erosions(P=0.0025).CONCLUSION:This study suggests that erosion and oozing,as well as abdominal pain,are useful indicators in the diagnosis of CMV gastritis following allo-SCT.

How old is too old? In vivo engraftment of human peripheral blood stem cells cryopreserved for up to 18 years-implications for clinical transplantation and stability programs

BACKGROUND Peripheral blood stem cells(PBSC)are commonly cryopreserved awaiting clinical use for hematopoietic stem cell transplant.Long term cryopreservation is commonly defined as five years or longer,and limited data exists regarding how long PBSC can be cryopreserved and retain the ability to successfully engraft.Clinical programs,stem cell banks,and regulatory and accrediting agencies interested in product stability would benefit from such data.Thus,we assessed recovery and colony forming ability of PBSC following long-term cryopreservation as well as their ability to engraft in NOD/SCID/IL-2 Rγnull(NSG)mice.AIM To investigate the in vivo engraftment potential of long-term cryopreserved PBSC units.METHODS PBSC units which were collected and frozen using validated clinical protocols were obtained for research use from the Cellular Therapy Laboratory at Indiana University Health.These units were thawed in the Cellular Therapy Laboratory using clinical standards of practice,and the pre-freeze and post-thaw characteristics of the units were compared.Progenitor function was assessed using standard colony-forming assays.CD34-selected cells were transplanted into immunodeficient mice to assess stem cell function.RESULTS Ten PBSC units with mean of 17 years in cryopreservation(range 13.6-18.3 years)demonstrated a mean total cell recovery of 88%±12%(range 68%-110%)and post-thaw viability of 69%±17%(range 34%-86%).BFU-E growth was shown in 9 of 10 units and CFU-GM growth in 7 of 10 units post-thaw.Immunodeficient mice were transplanted with CD34-selected cells from four randomly chosen PBSC units.All mice demonstrated long-term engraftment at 12 wk with mean34%±24%human CD45+cells,and differentiation with presence of human CD19+,CD3+and CD33+cells.Harvested bone marrow from all mice demonstrated growth of erythroid and myeloid colonies.CONCLUSION We demonstrated engraftment of clinically-collected and thawed PBSC following cryopreservation up to 18 years in NSG mice,signifying likely successful clinical transplantation of PBSC following long-term cryopreservation.

OMISSION OF DAY +11 METHOTREXATE DOES NOT APPEAR TO INFLUENCE INCIDENCE AND SEVERITY OF GRAFT-VERSUS- HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Objective: To explore the influence of omission of the day +11 dose of methotrexate (MIX) on the incidence and severity of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: From April 1997 to October 2002, 80 leukemia patients (46 men and 34 women aged from 12 to 56 years with a median age of 35) underwent allo-HSCT at our BMT unit. Among them, 58 patients received grafts from HLA-identical siblings, 8 from HLA one major antigen mismatched siblings and 14 from HLA-matched unrelated donors. All patients received a modified cyclosporine and short-course MTX regimen for GVHD prophylaxis, which included MTX 15 mg on day +1, and 10 mg on days +3 and +6 (MTX day +11 dose omitted) and cyclosporine given daily. Results: The overall incidence of grade I~IV acute GVHD was 57.5% (46/80 patients), with grade II~IV acute GVHD in 28 patients (35%) and grade III~IV acute GVHD in 7 patients (8.8%). Among 58 patients receiving grafts from HLA-identical siblings, 24 patients developed grade I~IV acute GVHD (41.4%), with grade II~IV acute GVHD in 13 patients (22.4%) and grade III~IV acute GVHD in 4 patients (6.9%). 2l out of 22 patients receiving grafts from HLA one major antigen mismatched siblings and HLA-matched unrelated donors developed grade I~IV acute GVHD (95.5%), with grade II~IV acute GVHD in 14 patients (63.6%) and grade III~IV acute GVHD in 3 patients (13.6%). Chronic GVHD occurred in 38 out of 56 evaluable patients (67.9%), with extensive form in 15 patients (26.8%) and limited form in 23 patients (41.1%). With a median follow-up of 960 days (range 180~1980 days), the probability of leukemia-free survival at 3 years was 61.3% for all patients. Conclusion: Our results suggest that the day +11 MTX can be omitted without a major deleterious effect on the incidence and severity of graft-versus-host disease after HLA-identical sibling transplantation as well as HLA one major antigen mismatched sibling and HLA-matched unrelated donor transplantation.