Peripheral Blood Hematopoietic Stem Cell Research Articles

65 - Infusion of Autograft Natural Killer Cells/CD14+hla-DRDIM Myeloid-Derived Suppressor Cells Ratio Predicts Survival in Non-Hodgkin Lymphoma Undergoing Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation (APHSCT)

65 - Infusion of Autograft Natural Killer Cells/CD14+hla-DRDIM Myeloid-Derived Suppressor Cells Ratio Predicts Survival in Non-Hodgkin Lymphoma Undergoing Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation (APHSCT)

371 - Filgrastim Biosimilars for Peripheral Blood Hematopoietic Stem Cell Mobilization in Healthy Donors: A Five-Year Experience From a University Hospital in Mexico

371 - Filgrastim Biosimilars for Peripheral Blood Hematopoietic Stem Cell Mobilization in Healthy Donors: A Five-Year Experience From a University Hospital in Mexico

Factors influencing platelet clumping during peripheral blood hematopoietic stem cell collection.

Platelet clumping is a common occurrence during peripheral blood hematopoietic stem cell (HSC) collection using the Spectra Optia mononuclear cell (MNC) protocol. If clumping persists, it may prevent continuation of the collection and interfere with proper MNC separation. This study is the first to report the incidence of clumping, identify precollection factors associated with platelet clumping, and describe the degree to which platelet clumping interferes with HSC product yield. In total, 258 HSC collections performed on 116 patients using the Optia MNC protocol were reviewed. Collections utilized heparin in anticoagulant citrate dextrose to facilitate large-volume leukapheresis. Linear and logistic regression models were utilized to determine which precollection factors were predictive of platelet clumping and whether clumping was associated with product yield or collection efficiency. Platelet clumping was observed in 63% of collections. Multivariable analysis revealed that a lower white blood cell count was an independent predictor of clumping occurrence. Chemotherapy mobilization and a lower peripheral blood CD34+ cell count were predictors of the degree of clumping. Procedures with clumping had higher collection efficiency but lower blood volume processed on average, resulting in no difference in collection yields. Citrate toxicity did not correlate with clumping. Although platelet clumping is a common technical problem seen during HSC collection, the total CD34+ cell-collection yields were not affected by clumping. WBC count, mobilization approach, and peripheral blood CD34+ cell count can help predict clumping and potentially drive interventions to proactively manage clumping.

Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation with IBu Precondition Regimen in Treatment for 11 Patients with Low to Intermediate Risk Acute Myeloid Leukemia

To evaluate safety and efficacy of autologous peripheral blood hematopoietic stem cell transplantation (auto-PBHSCT) with IBu precondition regimen consisting of high-dose idarubicin (IDA) and busulphan (Bu) for treatment of patients with low and intermediate risk acute myeloid leuekmia (AML). A total of 11 patients with AML (5 low and 6 intermediate risk patients) treated with auto-PBHSCT with IBu precondition regimen (IDA 20 mg/m2, continuous i.v. from d-13 to d-11, Bu 0.8 mg/kg/q6h i.v. for 2h, from d-5 to d-2) from March 2011 to July 2014 were analyzed retrospectively. Adverse effects and transplantation-related mortality (TRM) were evaluated. Kaplan-Meier analysis was performed to calculate the overall survival (OS), disease-free survival (DFS) and cumulative relapse rate (RR). Cox regression was performed for univariate analysis for DFS. Among the 11 patients, 10 patients obtained hematopoietic reconstitution, 1 patient died during transplantation, thus the TRM was 9.1%. The adverse effects were well tolerated. With median follow-up of 31.6 (8.7-52.5) months, 7 patients (63.3%) were alive, including 6 patients (54.5%) in continuous complete remission (CR). Median OS and DFS were not reached. The 3-year OS, DFS and RR were (57.7±16.3)%, (52.5±17.6)% and 47.5%, respectively. Univartiate analysis indicated that the age, sex, interval between diagnosis and transplantation, white blood cell count at diagnosis, risk-grouping (low or intermediate risk), disease status before transplantation (CR1 or CR2), and count of mononuclear cells for infusion all can not influence DFS(P>0.05, respectively). The treatment of auto-PBHSCT with IBu precondition regimen for low to intermediate risk AML patients is safe and effective.

Clinical analysis of autologous peripheral blood hematopoietic stem cell mobilization regimen in 61 lymphoma patients

Clinical analysis of autologous peripheral blood hematopoietic stem cell mobilization regimen in 61 lymphoma patients

Sustained Natural Killer Cell Recovery Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation Predicts Survival in Non-Hodgkin's Lymphoma

AbstractOur group recently reported a Phase III clinical trial (Porrata et al. Biology of Blood and Marrow Transplantation 2016; 22: 1017-1023) demonstrating that the infusion of the autograft-absolute lymphocyte count (A-ALC) and autograft natural killer cells (A-NKC) are survival prognostic factors in non-Hodgkin lymphoma (NHL) patients treated with autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). A limitation of our Phase III clinical trial was the short-term follow-up of just two years. Therefore, we evaluated longer follow-up and assessed the role of the infused A-ALC, infused A-NKC, and peripheral blood absolute natural killer cell count (ANKC) recovery on survival post-APBHSCT. Of the 122 patients that participated in the Phase III trial, 111 patients were able to complete APBHSCT and included in the current study. With a median follow-up of 57.2 months (range: 2.1-84.6 months), superior overall survival (OS) and progression-free survival (PFS) was observed in patients infused with an A-ALC ≥ 0.5 x 109 lymphocytes/kg [OS: HR = 0.429, 95%CI, 0.128-0.828, p < 0.01; and PFS: HR = 0.456, 95% CI, 0.177-0.863, p < 0.01] and an A-NKC ≥ 0.09 x 109 cells/kg [OS: HR = 1.58e-3, 95% CI, 1.046e-6-0.179, p < 0.003; and PFS: HR= 1.58e-3, 95% CI, 7.81e-7-0.064, p < 0.003]. Furthermore, patients that maintained an ANKC ≥ 250 cells/µl at 3 months, 6 months, 9 months and 12 months post-APBHSCT also experienced superior OS (Figure 1A) and PFS (Figure 1B)[OS and PFS times in months were evaluated from infusion date of stem cells]. In the multivariate analysis a sustained ANKC ≥ 250 cells/µl was an independent predictor for OS (HR = 0.013, 95% CI, 0.001-0.063, p < 0.0001) and PFS (HR = 0.014, 95% CI, 0.001-0.067, p < 0.0001). This study is an extension of our Phase III clinical trial showing that sustained innate immunity by measuring the ANKC correlated with superior clinical outcomes; thus providing a platform to develop innate immunity immunotherapeutic strategists directing to improve clinical outcomes post-APBHSCT in NHL patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Collection of Peripheral Blood Stem Cells in 118 Small Children Weighing 20 Kg or less: Experience of a Single Centre

Background: Peripheral blood stem cells (PBSC) are increasingly used as a source of stem cells for either autologous or allogeneic hematopoietic transplantation in children.Although technically similar to adult procedures, PBSC harvest may be difficult in young children, especially in the very small children.Aim: In this study, we aimed to evaluatethe safety and efficacy of harvesting peripheral blood hematopoietic stem cells in very small children,and to provide a guideline.Methods: Between Jan 2013 to Mar 2016, we evaluated 118 children weighing 20 kg or less, with the smallest patient weighing 11 kg. The patients had a median age of 59 months and included 72 children with thalassemia major and 46 young donors. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 10 mg/kg/day administered subcutaneously once a day and receiving oral calcium for five days before harvesting. Blood was withdrawn at a mean rate of 30-40 ml/min through a temporaryfemoral vein catheter (12 or 14 guage) to ensure adequate blood flow and returned through a larger catheter in a peripheral vein.Total nucleated cells(TNC) and CD34+ cells were estimated in the peripheral blood before collection of the apheresis product.Results: We collected sufficient products from all the children with one to three apheresis procedures. No serious complication was detected in all children and all aphereses were completed within 4 hours.The volume of blood per kilogram processed for each apheresis ranged from 55 to 160ml (median, 85ml). The median number of TNC and CD34+ cells collected were 12×108/kg and 15×106/kg per apheresis, respectively.Conclusions:We conclude that collection of PBSC is a safe and practical procedure in children, even in very small children. DisclosuresNo relevant conflicts of interest to declare.

Clinical Analysis of Adoptive Immunotherapy after Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation in B Lymphocyte Malignant Lymphoma

To investigate the efficacy of autologous peripheral blood hematopoietic stem cell transplantation(auto-PBHSCT) combined with adoptive immunotherapy for patients with B lymphocyte malignant lymphoma(ML). A total of 110 cases of ML treated with adoptive immunotherapy after auto-PBHSCT from January 2000 to December 2009 were enrolled in adoptive immunotherapy group (treated group), while 74 cases of ML treated without adoptive immunotherapy after auto-PBHSCT from January 1995 to December 1999 were used as control group. The efficacy of 2 groups were analyzed and compared, 110 case of ML in treated group included 78 cases of non-Hodgkin's lymphoma(NHL), 32 cases of Hodgkin's lymphoma(HL),74 cases of ML in control group included 52 NHL and 22 HL. All of the patients were treated sequentially with chemotherapy regimens for 6 courses. After that, all the patients received auto-PBHSCT. After hematopoietic reconstruction, the patients in treated group were given 6 courses of adoptive immunotherapy(rhIL-2 100 WU/day for 10 days monthly for each course), while the patients in control group were not given immunotherapy. All the patients were followed-up for more than 5 years. There was one patient in each group, who died of liver failure and cerebral hemorrhage respectively within 3 and 2 months, and all the other patients achieved hematopoietic reconstruction. Following-up for 1, 3, 5 years, the disease-free survival (DFS) rate in treated group was 97.3%,93.6%,87.3% while 91.9%, 73.0%, 64.9% in control group. Following-up for 3 and 5 years, there was very significant difference in DFS between 2 groups(P<0.01). The 1,3 and 5 year DFS rate of patients in stage I/II and III/IV in the treated group were 100%,100%,91.7% and 96.5%,91.9%,86.0% respectively while DFS of control group was 100%, 93.3%, 86.7% and 89.8%, 67.8%, 59.3%, there was a significant difference in 3 and 5 years DFS of III/IV stage patients between 2 groups (P<0.01). The 1,3 and 5 year DFS rate of HL patients were 100%, 93.8%,84.4% in treated group and 100%,72.7%,59.1% in control group respectively. There was significant difference in 3 and 5 years DFS of HL between 2 groups (P<0.05). The 1,3 and 5 year DFS rate of stage I/II HL patients were 100%,100%,88.9% in treated group and 100%,100%,80.0% in control group. The 1,3 and 5 year DFS of HL patients in stage III/IV was 100%,91.3%,82.6% and 94.1%,64.7%,52.9% respectively. There was significant difference in 3 and 5 years DFS of III/IV stage of HL patients between 2 groups (P<0.05). The 1,3 and 5 year DFS rate of NHL patients is 96.2%, 93.6%,88.5% in treated group and 90.4%,73.1%,65.4% in control group respectively. There was a significant difference in 3 and 5 years DFS of NHL between 2 groups(P<0.01). The 1,3 and 5 year DFS rate of stage I/II NHL patients was 100%, 100%, 93.3.9% in treated group and 100%, 90%, 90.0% in control group, respectively. The 1,3 and 5 year DFS of NHL patients in stage III/IV is 95.2%, 92.1%,87.3% and 88.1%,69.0%, 59.5% respectively. There was significant difference in 3 and 5 years DFS of III/IV stage NHL patients between 2 groups (P<0.05). Therapeutic efficacy is satisfactory for the patients of B lymphocyte ML treated with adoptive immunotherapy after auto-PBHSCT, especially benefited the patients of stage III/IV significantly.

Single nucleotide polymorphisms of the DGKB and VCAM1 genes are associated with granulocyte colony stimulating factor-mediated peripheral blood stem cell mobilization

We previously reported the association between LDL cholesterol level (LDL-C) and granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood (PB) hematopoietic stem cells (HSC). In this study, we investigated the association between gene single nucleotide polymorphisms (SNPs) involved in hematopoiesis and lipid level and PBHSC mobilization. In 46 patients who underwent peripheral blood stem cell harvest (PBSCH), we measured CD34-positive cells in PB and PBSCH, and the patients were classified into good, intermediate, or poor mobilizer groups based on the CD34-positive cell counts. And SNPs of the OR4C12, ENO1, RERE, DGKB, DSC3, VCAM1, CD44, and FADS1 genes were investigated. The frequency of the TT type of the DGKB gene was higher in the poor mobilizer group compared to other groups (p<0.05), whereas that of the CC type of the VCAM1 gene was high in the good mobilizer group (p<0.05). Association with the efficiency of HSC mobilization to PB were found in the SNPs of the DGKB gene involved in cell transport and SDF-1-induced migration ability and of the VCAM1 gene which is essential for HSC homing, suggesting that SNPs involved in cell migration ability might be partly involved in HSC mobilization to PB.

Effects of Hepatovirus B Infection on the Hematopoietic Stem Cell Collection and Implantment in Lymphoma Patients Received Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

To investigate the effect of hepatovirus B(HBV) infection on the hematopoietic stem cell collection and implantment in lymphoma patients received autologous peripheral hematopoietic blood stem cells transplantation. Clinical data of 40 lymphoma patients who received autologous peripheral hematopoietic blood stem cell transplantation between January 2006 and October 2014 was analyzed retrospectively. Among 40 patients with lymphoma 8 patients combined with HBV infection were prophylacticly given nucleoside analogues and 32 patients without HBV infection. The counts of mononuclear cells(MNC) and CD34 positive cells were collected and the hematopoietic reconstitution as well as overall survival rates and progress-free survival rates were detected and counted between patients with or without HBV infection. The counts of MNC and CD34 positive cells in all patients were standard, and there was no significant difference between patients with or without HBV infection. HBV wasn't reactivated among the 8 patients with HBV infection. The 1, 3 and 5 years' overall survival rates and progress-free survival rates of patients with HBV infection were 100%, 85.7%, 57.1% and 100%, 80%, 53%, respectively and the 1,3 and 5 years' overall survival rates and progress-free survival rates of patients without HBV infection were 100%, 88.9%, 82.1% and 90%, 90%, 90%, respectively. HBV infection may have no effect on the collection of stem cells and hematopoietic reconstitution. Prophylactic use of nucleoside analogues can effectively prevent the hepatitis B virus reactivation, moreover had no effect on the collection and hematopoietic reconstitution.

Effect of Different Procedures from Blood Cell Separators on Autologous PBSC Collection Efficiency

To observe the efficacy and adverse reactions of autologous PBSC collection when the autoPBSC procedure and MNC procedure of COBE Spectra cell separator and the MNC procedure of Spectra Optia cell separator were used. The autologous perepheral blood hematopoietic stem cells from 41 patients were collected by using autoPBSC procedure and MNC procedure of COBE Spectra blood cell separator and MNC procedure of Spectra Optia blood cell separator. The numbers of MNC and CD34+ cells collected by 3 collected procedure, the difference of hemoglobin (Hb) drop and platelet decrease, and the adverse reaction of patients were observed. When the whole blood processing and the collection time were basically same among these 3 groups, the MNC counts collected by MNC procedure of COBE Spectra and Spectra Optia were higher than that of AutoPBSC procedure of COBE Spctra, but the CD34+ cell count was lower than that collected by AutoPBSC procedure (P< 0.05). The final product volume collected by MNC procedure of COBE Spectra and Spectra Optia was bigger than that collected by AutoPBSC procedure. In comprission with MNC procedure of COBE Spectra cell seperator, the CD34+ count collected by MNC procedure of Spectra Optia Seperator did not show significant difference, but the CD34+ cell count collected by MNC procedure of Spectra Optia was higher than that collected by MNC procedure of COBE Spectra cell separator (P<0.05). The platelet count and hemoglobin level collected by MNC procedure of Spectra Optia were lower than those before collection. The adverse reactions in the 3 procedures were similar, and the patients could tolerate them. The AutoPBSC procedure of COBE Spectra and MNC procedure of Spectra Optia are better than MNC procedure of COBE Spectra for autologous peripheral blood hematopoietic stem cells collection. The loss of blood platelet and hemoglobin after collection is lowest in MNC procedure of Spectra Optia.

Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist

Mobilized peripheral blood (PB) has largely replaced bone marrow (BM) as the source of hematopoietic stem cells (HSC) for transplantation. Today, the administration of daily doses of granulocyte-colony stimulating factor (G-CSF) is routinely used for clinical mobilization, but its inherent disadvantages has driven efforts to identify faster and more effective agents based on single doses of small molecules. While the CXCR4 antagonist AMD3100 (Plerixafor/Mozobil) rapidly mobilizes HSC, it is only clinically effective when used in combination with G-CSF. Here, we have identified a novel small molecule antagonist (BOP; N-(Benzene-sulfonyl)-L-prolyl-L-O-(1-Pyrrolidinylcarbonyl)tyrosine) that targets both alpha9beta1 and alpha4beta1 integrins expressed by BM HSC. A single dose of BOP rapidly mobilized long-term multi-lineage reconstituting HSC, either alone or synergistically when used in combination with AMD3100. Impressively, HSC in PB mobilized using the BOP+AMD3100 combination effectively outcompeted equivalent numbers of HSC detected in equivalent volumes of PB mobilized with G-CSF. The significantly greater augmentation of HSC in PB using BOP+AMD3100 was recapitulated in a humanized NODSCIDIL2Rγ−/− model, demonstrating its applicability in the clinical context. Alpha4beta1 is ubiquitously expressed on all hematopoietic cells but the expression of alpha9beta1 is restricted to HSC/progenitors. Consistent with these results, we demonstrated inhibiting alpha4beta1 alone results in mobilization of WBC and progenitor cells but inhibiting alpha9beta1 is critical for effective HSC mobilization. Interestingly, BOP was also found to preferentially bind human and murine HSC and progenitors through endogenously primed/activated integrins within the endosteal niche. Differential targeting of endosteal HSC/progenitors was shown to be due to greater concentrations of integrin-activating metal ions (calcium, magnesium and manganese), with a metal ion concentration gradient emanating from the endosteal BM demonstrated. Together, these results identify and validate the integrin alpha9beta1 as a novel target for stem cell mobilization and highlights the combination of the small molecule integrin antagonist BOP with AMD3100 as an alternative, effective, rapid and transient mobilizer of long-term reconstituting HSC with promising clinical applications.

Collection of hematopoietic CD34 stem cells in rhesus macaques using Spectra Optia.

Nonhuman primates, particularly rhesus macaques, are ideal preclinical large animal models to investigate organ tolerance induction protocols using donor hematopoietic stem cells (HSCs) to induce chimerism. Their relatively small size poses some challenges for the safe and effective collection of peripheral blood HSCs through apheresis procedures. We describe our experiences using the Spectra Optia apheresis unit to successfully obtain HSCs from mobilized peripheral blood of rhesus macaques. Mobilization of peripheral blood HSCs was induced using granulocyte stimulating factor (G-CSF) and Mozobil. The Spectra Optia unit was used in 18 apheresis procedures in 13 animals (4.9-10 kg). Animal health was carefully monitored during and after the procedure. Changes in peripheral blood cells before, during and after procedure were determined by complete blood count and flow cytometry. The automatic settings of the Spectra Optia unit were applied successfully to the procedures on the rhesus macaque. All animals tolerated the procedure well with no mortality. Mobilization of HSCs were most consistently achieved using 50 μg/kg of G-CSF for 5 days and a single dose of Mozobil on the 5th day, followed by collection of cells 3 h after Mozobil injection. The final apheresis product contained an average of 23 billion total nucleated cells with 47% granulocytes, 3,871 million total CD3 cells and 77 million CD34 cells which resulted in an average of 10 million CD34+ cells/kg of donor weight. Apheresis of peripheral blood mobilized HSCs in rhesus macaques using Spectra Optia is a safe and effective procedure.

Biosimilar Filgrastim in Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization and Post-Transplant Hematologic Recovery.

To date, two kinds of Granulocyte Colony-Stimulating Factors (G-CSF) have been approved for autologous peripheral blood hematopoietic stem cell (PBSCs) mobilization and posttransplant hematologic recovery after high-dose chemotherapy: filgrastim (originator and biosimilar) and lenograstim. Biosimilar filgrastim has been approved on the basis of comparable efficacy and safety in clinical studies where it has been used as chemotherapy-induced febrile neutropenia prophylaxis, but no specific pre-registration studies have been published in the transplant setting. Hence, there is still general skepticism about the role of biosimilar G-CSFs in this setting of patients. This review of biochemical, pre-clinical and clinical data suggests significant comparability of biosimilar filgrastim with both originator filgrastim and lenograstim in autologous PBSCs mobilization and post-autograft hematologic recovery.

Identifying Inherited and Acquired Genetic Factors Involved in Poor Stem Cell Mobilization and Donor-Derived Malignancy

Analysis of the clinical characteristics of hematopoietic stem cell transplant (HSCT) donors has proven beneficial for identifying cases of heritable hematopoietic disorders. This study examines poor peripheral blood hematopoietic stem cell mobilization after granulocyte colony–stimulating factor administration among 328 donors as a potential marker for suspected familial predisposition to myeloid malignancies. Here, we present data comparing the clinical characteristics of poor-mobilizing versus nonpoor-mobilizing donors and the results of panel-based sequencing of hematopoietic genes in poor-mobilizing donors. From this analysis, we identified a novel case of a donor-derived myelodysplastic syndrome in an HSCT recipient that is consistent with clonal evolution of TET2-mutated clonal hematopoiesis of indeterminate potential (CHIP) within the donor. This study demonstrates the potential risk of using hematopoietic stem cells from a donor with CHIP and raises the question of whether there should be increased screening measures to identify such donors.

Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation for Treating Patient with Primary Cutaneous γΔ T Cell Lymphoma

To investigate the clinical characteristics of primary cutaneous γΔ T cell lymphoma and its treatment methods. The clinical data and treatment process of one woman case of primary cutaneous γ Δ T cell lymphoma diagnosed in our department were analysed. The multiple subcutaneous nodules were the main clinical features, the diagnosis of primary cutaneous γΔ T cell lymphoma was comfired by skin biopsy pathology. The immunophenotypes of lymphocytes showed CD20-, CD3+, CD4-, CD8-, CD56+, TIA-1+, Ki-67+ (about 60%); plasma cells kappa+(part)/lambda predominate+(part); histocytes CD4+, CD68/PGM1+; βF1-, epstein-barr (EB) virus showed negative EBER in situ hybridization. By means of the chemotherapy regimens containing L-Asparaginase, the complete remission (CR) was achieved. Then, the patients were given autologous hematopoietic stem cell transplantation. Neutrophils were implanted after 16 days, and platelet was implanted after 18 days. Now, the patient is still in remission. primary cutaneous γΔ T cell lymphoma is rare and easy to be misdiagnosed. This disease is aggressive and its prognosis is poor. The large dose chemotherapy with L-asparaginase shows a certain curative efficacy, the autologous hematopoietic stem cells can prolong survival time of the patient.

Multiple Giant Mushroom-like Tumors Inside the Stomach

Question: A 63-year-old woman presented with abdominal fullness and dizziness for 1 month. She had a history of acute myeloid leukemia (AML), M2, and received chemotherapy followed by allogeneic matched unrelated donor peripheral blood hematopoietic stem cell transplantation 5 years ago. She remained in complete hematologic remission upon bone marrow examination 6 months ago. The physical examination showed epigastric tenderness. The blood tests were unremarkable except for macrocytic anemia (hemoglobin, 11.0 g/dL; mean corpuscular volume, 104.9 fL). The vitamin B12 and folic acid levels were within normal limit (vitamin B12, 707 pg/mL; folic acid, 3.16 ng/mL). Esophagogastroduodenoscopy showed multiple 2to 6-cm mushroom-like tumors over the fundus and body, with hyperemic mucosa, superficial ulceration, and easily touch bleeding in some of them (Figure A). Biopsies were obtained. Abdominal computed tomography scan revealed multiple mass lesions up to 6 cm over the fundus and gastric body (Figure B). Positron emission tomography scan showed focal hot area at stomach, which was suspected to be inflammation or a malignancy (Figure C). What is the most likely diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Hepatitis B Virus Replication in CD34+ Hematopoietic Stem Cells From Umbilical Cord Blood.

BackgroundHepatitis B virus (HBV) is a hepatotropic virus that can infect extrahepatic tissue. Whether hematopoietic stem cells (HSCs) can be infected by HBV and serve as a potential virus reservoir is still unknown. In this study, the susceptibility of CD34+ HSCs to HBV was investigated.Material/MethodsCord blood–derived CD34+ HSCs were exposed to HBV in vitro, and immunocytochemistry, transmission electron microscopy, and RT-PCR were used to identify viral-related proteins and specific viral genomic sequences. Then, CD34+ HSCs were challenged by different titers of HBV, and intracellular and supernatant HBV DNA, and hepatitis B surface antigen (HBsAg) levels, were examined. In addition, CD34+ peripheral blood stem cells (PBSCs) from chronic HBV carriers were isolated and cultured, and HBV DNA levels were measured.ResultsHBV-infected CD34+ cells showed positive signals for HBsAg by DAB staining and TRITC staining, and HBV particles were identified. RT-PCR results showed that the 403 bp PCR products corresponding to the amplified hepatitis B S gene fragment were observed in CD34+ HSCs infected by HBV. In addition, supernatant and intracellular HBV DNA increased with the proliferation of CD34+ HSCs. Similar results were obtained from intracellular HBsAg quantification tests. In addition, HBV DNA levels both in cells and in supernatants of CD34+ PBSCs increased proportionally, and the increments of HBV DNA in the supernatants paralleled those found in cells.ConclusionsHBV can replicate in CD34+ HSCs in cord blood or peripheral blood of chronic HBV carriers.

Therapeutic Efficacy Analysis of Allogeneic Peripheral Blood Hematopoietic Stem Cell Transplantation for 14 Adult Patients with T Lymphoblastic Lymphoma

To investigate the therapeutic efficacy of allogeneic peripheral blood hematopoietic stem cell transpdantation (allo-HSCT) for T lymphoblastic lymphoma (T-LBL). The clinical data of 14 adult patients with T-LBL treated with allo-HSCT were collected, the hematopoietic reconstruction, survival and relapse, as well as overall survival (OS) rate, event-free survival (EFS) rate of 1, 3 and 5 years were analysed retrospectively. All the patients were engrafted with neutrophil successfully, the median time of absolute neutrophil count >0.5 × 10(9)/L was 13 (10-19) d; 13 patients were engrafted with platelets successfully, the median time of Plt count >20 × 10(9)/L was 17 (12-62) days. The acute GVHD occurred in 6 patients, but among them only 1 case with 3 grade of aGVHD; out of 14 patients, 5 developed chronic GVHD. The transplant-related mortality at 100 days was 7.1% (1/14), mainly from coronary heart disease and pulmonary infection. The median follow-up time was 26.5 months, the estimated 1, 3 and 5 year OS rate was 85.7%, 47.6% and 38.1%, respectively, and estimated 1, 3 year EFS rate was 85.7%, 34.4% and 34.1%, respectively. The relapse rate was 42.8% (6/14) and the median relapse time was 22.5% months after transplantation. Up to now, 7 patients still survive, 1 patient out of them have survived for 103 months. The allo-HSCT is a safe and effective method for treatment of T-LBL.

Clinical Summarization of Allogeneic Hematopoietic Stem Cell Transplantation for Leukemia: A Report of 100 Cases

To analyze the treatment outcome of a consecutive series of 100 leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of leukemia patients received allo-HSCT were analyzed retrospectively, the therapeutic efficacy was summarized. 100 evaluable cases of leukemia included 47 cases of AML, 33 cases of ALL, 2 cases of AL (biphenotypic), 16 CML and 2 CMML. Before transplantation, 76 cases were in first complete remission, 9 cases in second or greater complete remission and 15 cases in non-remission or relapse. All the patients received peripheral blood hematopoietic stem cell transplantation (PBHSCT). The conditioning regimen of human leukocyte antigen (HLA)-matched allo-HSCT group was modified BuCy, but in HLA-mismatched group Fludarabine and anti-human thymocyte globulin (ATG) was added. CsA+MTX regimen was used for prophylaxis of graft-versus-host disease (GVHD) in HLA-identical allo-HSCT, while additional MMF was added in HLA-mismatched group. The average time of follow-up was 13 months. At the last follow-up, 66.0% (66/100) patients survived, 53.0% (53/100) patients survived without leukemia, 28.0% (28/100) patients relapsed and 34.0% (34/100) patients died, 44.1% patients of them died from infectious pulmonary complications. During transplantation, 65.0% of the patients were suffered from lung infection. The overall survival (OS) and disease-free survival (DFS) of all cases was 60.9% and 48.8%, respectively. The recurrence rate was significantly higher in non-remission (66.7%) than in CR (21.2%) patients (P < 0.05). The cumulative incidence of GVHD in HLA-mismatched transplantation was 60.8%, which was significantly higher than that of HLA-matched transplantation (38.8%) (P < 0.05). Allo-HSCT can cure a significant proportion of leukemia patients, especially for those in CR status. Since the incidence of infectious pulmonary complications after allo-HSCT is still high, much more attention should be paid to it. The comprehensive prognosis of HLA-matched transplantation is better than the HLA-mis-matched transplantation.