Abstract:Our study shows strong differences in terms of quantitative and qualitative cellular composition between several blood or graft sources, possibly explaining the differences observed in terms of outcomes after transplant.
“…In line with our findings, Rodriguez-Cortes et al describe an extensive increase of leukocytes after G-CSF mobilization, including a moderate increase of lymphocytes [ 15 ]. Our observations are also consistent with data from Chevallier et al [ 16 ] and Sica et al [ 17 ]. Fig.…”
Section: Resultssupporting
confidence: 94%
“…Nawa et al [ 39 ] described a reduced stimulatory potential of monocytes from G-CSF mobilized donors in mixed lymphocyte reactions, potentially indicating reduced potential of such monocytes to stimulate T-cell responses; however, they described that T-cell function was not directly altered by G-CSF mobilization. Others described that the cell count of dendritic cells per µl PB is increased after mobilization [ 15 , 16 ] bearing the advantage that these dendritic cells as APCs may contribute to effective expansion of antigen-specific T cells in protocols such as ours. During our cultivation process, however, G-CSF is absent, and we observed that 9-day cultures from G-CSF mobilized donors resulted in equal relative expansion of virus-specific T cells in comparison to cultures from non-mobilized donors, and T-cell function, as measured in ELISpot, was even better for mobilized donors.…”
BackgroundA major complication after allogeneic hematopoietic stem cell transplantation (aSCT) is the reactivation of herpesviruses such as cytomegalovirus (CMV) and Epstein–Barr virus (EBV). Both viruses cause significant mortality and compromise quality of life after aSCT. Preventive transfer of virus-specific T cells can suppress reactivation by re-establishing functional antiviral immune responses in immunocompromised hosts.MethodsWe have developed a good manufacturing practice protocol to generate CMV/EBV-peptide-stimulated T cells from leukapheresis products of G-CSF mobilized and non-mobilized donors. Our procedure selectively expands virus-specific CD8+ und CD4+ T cells over 9 days using a generic pool of 34 CMV and EBV peptides that represent well-defined dominant T-cell epitopes with various HLA restrictions. For HLA class I, this set of peptides covers at least 80% of the European population.ResultsCMV/EBV-specific T cells were successfully expanded from leukapheresis material of both G-CSF mobilized and non-mobilized donors. The protocol allows administration shortly after stem cell transplantation (d30+), storage over liquid nitrogen for iterated applications, and protection of the stem cell donor by avoiding a second leukapheresis.ConclusionOur protocol allows for rapid and cost-efficient production of T cells for early transfusion after aSCT as a preventive approach. It is currently evaluated in a phase I/IIa clinical trial.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1498-3) contains supplementary material, which is available to authorized users.
“…In line with our findings, Rodriguez-Cortes et al describe an extensive increase of leukocytes after G-CSF mobilization, including a moderate increase of lymphocytes [ 15 ]. Our observations are also consistent with data from Chevallier et al [ 16 ] and Sica et al [ 17 ]. Fig.…”
Section: Resultssupporting
confidence: 94%
“…Nawa et al [ 39 ] described a reduced stimulatory potential of monocytes from G-CSF mobilized donors in mixed lymphocyte reactions, potentially indicating reduced potential of such monocytes to stimulate T-cell responses; however, they described that T-cell function was not directly altered by G-CSF mobilization. Others described that the cell count of dendritic cells per µl PB is increased after mobilization [ 15 , 16 ] bearing the advantage that these dendritic cells as APCs may contribute to effective expansion of antigen-specific T cells in protocols such as ours. During our cultivation process, however, G-CSF is absent, and we observed that 9-day cultures from G-CSF mobilized donors resulted in equal relative expansion of virus-specific T cells in comparison to cultures from non-mobilized donors, and T-cell function, as measured in ELISpot, was even better for mobilized donors.…”
BackgroundA major complication after allogeneic hematopoietic stem cell transplantation (aSCT) is the reactivation of herpesviruses such as cytomegalovirus (CMV) and Epstein–Barr virus (EBV). Both viruses cause significant mortality and compromise quality of life after aSCT. Preventive transfer of virus-specific T cells can suppress reactivation by re-establishing functional antiviral immune responses in immunocompromised hosts.MethodsWe have developed a good manufacturing practice protocol to generate CMV/EBV-peptide-stimulated T cells from leukapheresis products of G-CSF mobilized and non-mobilized donors. Our procedure selectively expands virus-specific CD8+ und CD4+ T cells over 9 days using a generic pool of 34 CMV and EBV peptides that represent well-defined dominant T-cell epitopes with various HLA restrictions. For HLA class I, this set of peptides covers at least 80% of the European population.ResultsCMV/EBV-specific T cells were successfully expanded from leukapheresis material of both G-CSF mobilized and non-mobilized donors. The protocol allows administration shortly after stem cell transplantation (d30+), storage over liquid nitrogen for iterated applications, and protection of the stem cell donor by avoiding a second leukapheresis.ConclusionOur protocol allows for rapid and cost-efficient production of T cells for early transfusion after aSCT as a preventive approach. It is currently evaluated in a phase I/IIa clinical trial.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1498-3) contains supplementary material, which is available to authorized users.
“…BM contains larger volume, more red blood cells, but less white blood cells and HSCs as compared to PBSC (38). Due to the large amounts of red blood cells in BM, ABO mismatch between donor and recipient have to be considered.…”
Hematological malignancies account for approximately 9.5% of new cancers diagnosed annually. Lymphoma is the most frequent of all known categories of hematological malignancies. Worldwide, extensive research has focused on this type of cancer. However, new treatments are investigated in various clinical as well as pre-clinical studies. Hematopoietic stem cell transplantation (HSCT) is a recent and upcoming treatment strategy for patients with hematopoietic malignancies and inborn errors of metabolism or immune deficiencies. Recent studies have revealed that successful clinical outcome of this treatment strategy depends on multiple factors including the protocol applied, disease under treatment, health of the patient, source of the grafts, severity of complications such as graft versus host disease during grafting and associated infections. The scope of this review is to achieve greater understanding of various clinical effects of the disease and related mechanisms. The electronic database Pubmed was searched for pre-clinical as well as clinical controlled trials reporting efficacy of the HSCT against hematological malignancies.
“…BMT, bone marrow transplantation; CBT, cord blood transplantation; cGVHD, chronic graft-versus-host disease; CI, confidence interval; HCT, haematopoietic cell transplantation; IST, immunosuppressive treatment; PBSCT, peripheral blood stem cell transplantation; TSCM, T memory stem cells. blood grafts compared to those in bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood grafts for HCT (Chevallier et al, 2013). In fact, TSCMs were found at very low levels in cord blood (Gattinoni et al, 2011).…”
Section: Discussionmentioning
confidence: 96%
“…These findings observed in CBT were not consistent with previous studies, which suggested that CD4 + T cell reconstitution after CBT with ATG (Jacobson et al , ; Bejanyan et al , ) or without ATG (Kanda et al , ) was delayed compared to allogeneic HCT from other graft sources. Given that the T‐cell receptor rearrangement excision circles (TREC) were of a low copy number in TSCMs compared with TNs (Gattinoni et al , ), the higher proportion of CD4 + TSCMs early after CBT may be partly due to significantly higher proportions of TNs and CD4 + T cells in cord blood grafts compared to those in bone marrow and granulocyte colony‐stimulating factor‐mobilized peripheral blood grafts for HCT (Chevallier et al , ). In fact, TSCMs were found at very low levels in cord blood (Gattinoni et al , ).…”
Summary
T memory stem cells (TSCMs) are a subset of primitive T cells capable of both self‐renewal and differentiation into all subsets of memory and effector T cells. Therefore, TSCMs may play a role in immune reconstitution and graft‐versus‐host disease (GVHD) in patients receiving allogeneic haematopoietic cell transplantation (HCT). We conducted a cross‐sectional study to evaluate the proportions, absolute counts, phenotypes and functions of TSCMs in 152 adult patients without disease recurrence at least 12 months after undergoing HCT. CD4+ TSCMs were negatively correlated with number of months after transplantation in HCT patients that received cord blood transplantation, but not in patients that received bone marrow transplantation or peripheral blood stem cell transplantation. The proportions and absolute counts of CD4+ TSCMs and expression levels of inducible co‐stimulator (ICOS) in CD8+ TSCMs were significantly higher in patients with mild and moderate/severe cGVHD compared to patients without cGVHD. These data suggested that, more than 12 months after allogeneic HCT, the kinetics of CD4+ TSCMs were dependent on the type of donor source, and further that CD4+ TSCMs and ICOS levels in CD8+ TSCMs were associated with cGVHD.
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