scholarly journals Use of a T cell-specific monoclonal antibody, T10B9, in a novel allogeneic stem cell transplantation protocol for hematologic malignancy high-risk patients

2004 ◽  
Vol 10 (12) ◽  
pp. 858-866 ◽  
Author(s):  
John S. Thompson ◽  
Claire Pomeroy ◽  
Richard J. Kryscio ◽  
Stephen A. Brown ◽  
Donna Reece ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hematologic Malignancy ◽  
Specific Monoclonal Antibody ◽  
Risk Patients

Human Cytomegalovirus: Degranulation Is a Prominent Feature of Functionally Impaired pp65- and IE-1-Specific T-Cells in Patients after Allogeneic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2572-2572
Author(s):  
Stephan Fuhrmann ◽  
Susanne Ganepola ◽  
Lutz Uharek ◽  
Eckhard Thiel ◽  
Wolf-Dieter Ludwig ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Human Cytomegalovirus ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Cmv Reactivation

Abstract Human cytomegalovirus (CMV) reactivation and disease is still a frequent complication after allogeneic stem cell transplantation (allo SCT). It is well accepted that T-cell immunity is mandatory to control CMV infection and disease and much effort has been put into the development of cell-based monitoring assays. Nevertheless, no reliable marker for protective immunity has been established to date. Most studies use one CMV model antigen (pp65) to compare the frequencies of cytokine producers (mainly IFNg) or multimer-specific T-cells. Methods: In total, we recruited 16 patients after allo SCT, (7 high risk, 9 standard risk pts.). We used 8-colour flow cytometry to detect degranulation (mobilized CD107a/b), intracellular IFNg, TNFa, IL-2 production and CD28-expression in peptide pool stimulated pp65 and IE-1 specific CD8 T-cells. Results were compared to 7 healthy CMV exposed donors. Results: Degranulation identifies the highest percentage of CMV-specific T-cells in allo-transplanted patients (pp65: 0,94% degranulation and 0,31% IFNg; IE-1: 1,44% degranulation and 0,87% IFNg, mean frequency). These T-cells are relatively cytokine deficient compared to those in healthy donors (cytokine-production/degranulation ratio: SCT=0,42, healthy=0,72 for pp65, p=0,048; SCT=0,61, healthy= 1,00 for IE-1, p=0,133, U-test). The cytokine expression pattern differs between antigens used for stimulation, for example more IL-2-producers could be detected in the pp65 specific compartment (12,5% for pp65 and 4,5% for IE-1 of all activated CD8 T-cells, p=0,015). Conclusion: This study demonstrates that degranulation is the most prominent marker of CMV-specific T-cells (pp65 and IE-1) in allo SCT patients. Looking at IFN-g producers only may underestimate the frequencies of CMV specific T-cells in this setting. Furthermore, these subsets have a divergent functionality in transplant recipients compared to healthy individuals. Our data challenge the concept of enumerating CMV specific T-cells to estimate immunity. We rather propose measuring functional differences in the T-cell response may help to identify patients with a high risk of CMV reactivation. A careful dissection of these differences is a prerequisite for the development of monitoring tools and adoptive T-cell transfer.

Rapid Risk-Profiling Including Fast Donor Search within a Multi-Center Trial Allows for Early Allogeneic Stem Cell Transplantation during Aplasia in Patients with High-Risk Acute Myeloid Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2767-2767 ◽  
Author(s):  
Markus Andreas Schaich ◽  
Monika Fuessel ◽  
Martin Bornhaeuser ◽  
Christian Thiede ◽  
Brigitte Mohr ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Therapy ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donor ◽  
High Risk Patients ◽  
Risk Profiling ◽  
Risk Patients

Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for most high-risk patients with acute myeloid leukemia (AML). However, many high-risk patients regenerate with blasts or relapse early after induction therapy. Thus, consolidation with allogeneic HSCT in first CR is often not possible. Performing allogeneic HSCT within induction therapy can circumvent these problems and may furthermore reduce cumulative toxicity in high risk patients. Therefore, the prospective randomized treatment trial AML2003 for patients <= 60 years was set up, to investigate the feasibility and value of an intensified treatment strategy, i.e. early allogeneic stem cell transplantation in aplasia after induction therapy, for high risk AML patients in a multi-center setting. To achieve this goal, rapid analysis of cytogenetics, FLT3 status and HLA-types of the patient and possible family donors is of utmost importance. This fast search diagnostics together with routine analyses of morphology and immunophenotyping is accomplished centrally in all enclosed patients. Furthermore, in all patients the likelihood to find an unrelated donor is checked by an internet search in the BMDW database. Within the first 8 months 107 AML patients with a median age of 48 (17–60) years were included in the study. Fast search diagnostics was complete within a median of 15 (range 5–31) days after arrival of the bone marrow samples for all patients. 57/107 patients were randomized into the intensified treatment arms. Out of these 25 (44%) patients with high risk characteristics have been identified. A suitable related or unrelated donor was found for 22 (88%) of those high-risk patients. Nine of those high risk patients with a donor (41%) received early allogeneic stem cell transplantation in aplasia after the first (n=4) or the second (n=5) induction therapy course on an intend to treat basis within the protocol. Three were transplanted with stem cells of related and six of unrelated donors. The preparative regimen consisted of melphalan 150mg/m2 and fludarabine 150mg/m2. So far no treatment associated death had to be recognized. These encouraging preliminary results show that fast risk-profiling and early donor-search is feasible in a large multi-center study. This leads to a significant proportion of early allogeneic stem cell transplants in aplasia after induction therapy within the group of high risk AML patients, which may improve the disastrous prognosis of this group of patients in the future.

Upfront Allogeneic Stem Cell Transplantation for Remission Induction in High-Risk Acute Myeloid Leukemia Patients within the Randomized Multi- Center Trial AML2003.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 978-978 ◽  
Author(s):  
Markus Schaich ◽  
Thomas Illmer ◽  
Walter E. Aulitzky ◽  
Martin Bornhaeuser ◽  
Martin Griesshammer ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Therapy ◽  
Allogeneic Stem Cell Transplantation ◽  
Allogeneic Transplantation ◽  
Remission Induction ◽  
High Risk Patients ◽  
Risk Patients

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option for most high-risk patients with acute myeloid leukemia (AML). However, many high-risk patients regenerate with blasts or relapse early after induction therapy. Thus, consolidation with allogeneic HSCT in first CR is often not possible. Performing upfront allogeneic HSCT for remission induction as part of induction therapy has the potential to circumvent these problems and might furthermore reduce cumulative toxicity in high-risk patients. Therefore, in 2003 we started a prospective multicenter randomized trial that investigates both the feasibility and efficacy of upfront allogeneic stem cell transplantation for remission induction in high-risk AML patients. Methods: The AML2003 study compares in a randomized fashion an intensified treatment approach using upfront allogeneic transplantation in high risk patients as part of the induction therapy (IT) during marrow aplasia achieved by DA (daunorubicin 60 mg/ m2 – day 3–5; cytarabine 100 mg/m2 – day1–7) to a “conventional” treatment strategy, which allows for allogeneic transplantation only in patients achieving remission after two induction courses (DA). To do this, rapid analysis of cytogenetics, FLT3 status and HLA-DNA-typing of the patient and possible family donors is of utmost importance. This “fast search diagnostics” together with routine analyses of morphology and immunophenotyping is accomplished centrally in all enclosed patients. The dose-reduced preparative regimen for upfront allogeneic stem cell transplantation within induction therapy consisted of melphalan 150mg/m2 and fludarabine 150mg/m2. Results: Until the last update we recruited 679 patients <= 60 years with de novo (n=570) or secondary (n=109) AML. Out of 340 patients randomized for an intensified treatment approach we identified 139 patients (41%) with high-risk defined by cytogenetic criteria (n=87), FLT3 status (n=15) or day 15 blast count (n=37). Fast search strategy revealed HLA identical donors (related or unrelated) for 106 patients. Consequently, 78 high-risk AML patients assigned to the intensified treatment strategy received allogeneic transplantation. Upfront allogeneic stem cell transplantation for remission induction was feasible in 28 high-risk AML patients during marrow aplasia after IT1 (n=10) or IT2 (n=18), respectively. Fifteen of these patients received unrelated grafts. Conclusions: These preliminary results show that rapid risk profiling and fast donor-search is feasible in a large multi-center study. This leads to a significant proportion of upfront allogeneic stem cell transplants as part of the induction therapy within the group of high-risk AML patients, which may improve the disastrous prognosis of this group of patients in the future.

scholarly journals Evolution of the donor T-cell repertoire in recipients in the second decade after allogeneic stem cell transplantation

Blood ◽  
2011 ◽  
Vol 117 (19) ◽  
pp. 5250-5256 ◽  
Author(s):  
Robert Quan Le ◽  
J. Joseph Melenhorst ◽  
Minoo Battiwalla ◽  
Brenna Hill ◽  
Sarfraz Memon ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Hematologic Malignancy ◽  
Lymphocyte Function ◽  
Significant Difference

Abstract After allogeneic stem cell transplantation (SCT), T lymphocyte function is reestablished from the donor's postthymic T cells and through thymic T-cell neogenesis. The immune repertoire and its relation to that of the donor have not been characterized in detail in long-term adult SCT survivors. We studied 21 healthy patients in their second decade after a myeloablative SCT for hematologic malignancy (median follow-up, 12 years). Immune profiles were compared with donor samples cryopreserved at transplant and beyond 10 years from SCT. Only one recipient was on continuing immunosuppression. Compared with the donor at transplant, there was no significant difference in CD4, CD8, natural killer, and B-cell blood counts. However, compared with donors, recipients had significantly fewer naive T cells, lower T-cell receptor excision circle levels, fewer CD4 central memory cells, more effector CD8+ cells, and more regulatory T cells. TCR repertoire analysis showed no significant difference in complexity of TCRVβ spectratype between recipients and donors, although spectratype profiles had diverged with both gain and loss of donor repertoire peaks in the recipient. In conclusion, long-term allogeneic SCT survivors have subtle defects in their immune profile consistent with defective thymic function but compatible with normal health. This study is registered at http://www.clinicaltrials.gov as NCT00106925.

A cost and resource utilization analysis of micafungin bridging for hemato-oncological high-risk patients undergoing allogeneic stem cell transplantation

2015 ◽  
Vol 94 (6) ◽  
pp. 526-531 ◽  
Author(s):  
Sebastian M. Heimann ◽  
Maria J.G.T. Vehreschild ◽  
Oliver A. Cornely ◽  
Bernd Franke ◽  
Michael von Bergwelt-Baildon ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Resource Utilization ◽  
Allogeneic Stem Cell Transplantation ◽  
High Risk Patients ◽  
Risk Patients
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