A Phase I/II Study of Xcellerated T Cells™ after Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 925-925
Author(s):  
David Siegel ◽  
Ravi Vij ◽  
Robert A. Vescio ◽  
Ivan M. Borrello ◽  
Thomas G. Martin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Cell Receptor ◽  
Post Transplant

Abstract Background: Previous studies have demonstrated a correlation between survival and lymphocyte recovery following autologous transplantation in subjects with multiple myeloma and other malignancies (Porrata et al., Blood 2001). We initiated a trial in the transplant setting to evaluate the activity of T cells activated and expanded ex vivo with the Xcellerate™ Process, which uses anti-CD3 and anti-CD28 antibody-coated magnetic beads (Xcyte™ -Dynabeads®). Methods: Following induction therapy, patients underwent leukapheresis to collect peripheral blood mononuclear cells for the Xcellerate Process. Patients then underwent stem cell mobilization and collection, followed by high dose melphalan (200 mg/m2). Three days following peripheral blood stem cell infusion, subjects received 50–100 x 109 Xcellerated T Cells. Results: 36 subjects were treated. The median last f/u visit is 180 days post-transplant (range 90–450). A WaveBioreactor-based Xcellerate III Process, which was instituted in the last 18 subjects, resulted in 249 ± 90 fold (mean ± SD) T cell expansion. There were 93.6 ± 0.8 x 109 cells infused, which were 97.6 + 4.0% T cells. There were no Grade 3 or 4 acute infusional toxicities. Days of neutropenia and thrombocytopenia were 5 (3–43) and 4.5 (0–128) respectively [median (range)]. There were a median of 2 (range 0–14) units of packed red blood cell transfusions in 18/31 (58%) of subjects and a median of 0 (range 0–22) platelet transfusions in 15/31 (48%) of subjects. There were serious or Grade 3 infections in 5/29 (17%) of subjects, and mucositis in 5/29 (17%) of subjects (all ≤ Grade 2). Median days of hospitalization were 16 (range 10–70). Lymphocyte recovery was rapid, with counts reaching > 500/mm3 generally within 1–2 days following T cell infusion. Historically, lymphocyte recovery to > 500/mm3 usually does not occur for 3 or more weeks post-transplant. The rapid lymphocyte recovery included both CD4+ and CD8+ T cells. The mean (± SEM) CD4+ T cell count at 90 days post-transplant was 1,210 ± 80/mm3, significantly higher than that for historical controls receiving the same treatment regimen without Xcellerated T Cells (198 ± 72). The T cell receptor repertoire measured 25 days after the Xcellerated T Cell infusion demonstrated a normal pattern (n = 4/5). This is in contrast to the severe skewing of T cell receptor diversity observed in myeloma subjects following standard autologous stem cell transplantation (Mariani et al, BJH 2001). In 35 evaluable patients, preliminary results demonstrated 6% CRs, 46% VGPRs, 34% PRs, and 11% with PD, using the M-protein at diagnosis as reference. There have been no reported deaths to date. Conclusions: In multiple myeloma subjects, administration of Xcellerated T Cells following high-dose chemotherapy and autologous stem cell transplantation leads to rapid lymphocyte recovery and appears to restore a normal T cell receptor repertoire. The majority of subjects achieve clinical responses in the autologous transplant setting.

Clonality Analysis as a Tool To Study the Immunologic Reconstitution with Leukemia Patients Following Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5020-5020
Author(s):  
Xin Du ◽  
Yangqiu Li ◽  
Jianyu Weng ◽  
Zesheng Lu ◽  
Rong Xie ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Gene Repertoire ◽  
Hematopoietic Stem ◽  
Receptor Repertoire

Abstract Introduction The extensive diversity of the mature T-cell receptor(TCR) is determined primarily by the complementarity-determining regions (CDR3) of the TCR. The CDR3 of both TCRα and TCRβ genes is generated by extensive rearrangement and fusion between the V,D,and J segments and by random insertion and deletion of junctional nucleotides, which yields final products that are quite heterogeneous in size. As a result of these gene rearrangements, each T cell has a unique TCR and the diversity of the T-cell repertoire at any specific time can be characterized by the examination of CDR3 within that population. Using CDR3 spectratying technique, normal individuals demonstrate a highly diverse and polyclonal The aim of our study was to evaluate to investigate restricted expansion of TCR Vβ gene repertoire and the reconstitution of T cell receptor repertoire following allogeneic hematopoietic stem cell transplantation. Methods Patients Ten patients(9 males, 1 females; median age 31 years,range18–45) with 6 chronic myeloid leukemia-chronic phase and 4 cases of acute myelogenous lenkemia(CR1) who underwent HLA-matching sibling or unrelated BMT and/or peripheral blood stem cell transplantation (PBSCT) at our department between July 1999 and May 2000 were considered evaluable restricted expansion of TCR Vβ gene repertoire, the reconstitution of T cell receptor repertoire and oligoclonal T Cell Expansion in Chronic Graft-Versus-Host Disease. RT-PCR and Genes scan analysis (CDR 3 length analysis). Results Only 2-18Vβ genes were found in samples from these ten patients within one year, and there are different distribution in different patients. TCR repertoire complexity was abnormal in all patients, parts of the genes were expansion and part of them were suppressed. Samples from 9 patients with GVHD show V β3 in 7 cases, V β 8 and V β 23 in 6 patients. The results of genescan show that the PCR production of peripheral blood samples from these patients disply oligoclonal. Only 5–22Vβ subfamily T cells were found in samples from these patients whose transplantation more than one year. TCR repertoire complexity was abnormal in all patients. Discussion Following allogeneic BMT, regeneration of T-cell populations with a diverse repertoire can occure by at least two mechanisms: One mechanism is a thymic-dependent pathway, which presumably involves both negative and positive selection and recapitulates fetal ontogeny. Alternatively, regeneration of peripheral T cells may occur through thymic-independent mechanisms. All patients had marked abnormalities in their spectratypes, only 5-22Vβ subfamily T cells were found in samples from these patients, most of it was influenced after transplant, although the number of circulating CD3+ T lymphocytes in these patients have restored at normal lever by flow cytometic analysis, but the CD4+ T cell subset returned slowly in these patients resulting in an inversion of the normal CD4/CD8 ratio for more than 1 year after tuansplantation. Therefore, the analysis of TCRVβ subfamily is a usuaful methods and techniques for monitoring immune reconstitution after transplant.

Vaccination with DC/Multiple Myeloma Fusions in Conjunction with Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 578-578
Author(s):  
David Avigan ◽  
Jacalyn Rosenblatt ◽  
Baldev Vasir ◽  
Zekui Wu ◽  
Adam Bissonnette ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Regulatory T Cells ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Tumor Immunity ◽  
Myeloma Cells ◽  
Post Transplant

Abstract Autologous transplantation results in the transient reversal of tumor mediated tolerance due to the reduction in disease bulk, the depletion of regulatory T cells, and in the increased presence of tumor reactive lymphocytes during the period of lymphopoietic reconstitution. As a result, cancer vaccines are being explored as a means of targeting residual myeloma cells following stem cell transplant. We have developed a cancer vaccine in which patient derived tumor cells are fused with autologous dendritic cells (DCs). In this way multiple tumor antigens are presented in the context of DC mediated costimulation. We are conducting a study in which patients with multiple myeloma (MM) undergo stem cell transplantation followed by vaccination with 3 doses of DC/MM fusions. DCs were generated from adherent mononuclear cells cultured with GM-CSF and IL-4 for 5–7 days and matured with TNFa. DCs strongly expressed costimulatory and maturation markers. Myeloma cells were isolated from bone marrow aspirates and were identified by their expression of CD38, CD138, and/or MUC1. DC and MM cells were fused with polyethylene glycol as previously described and fusion cells were quantified by determining the percentage of cells that coexpress unique DC and myeloma antigens. To date, 19 patients have been enrolled and 18 have completed vaccine generation. Mean yield of the DC and myeloma preparations was 1.84 × 108 and 8.3 × 107 cells, respectively. Mean fusion efficiency was 40% and the mean cell dose was 4.3 × 106 fusion cells. As a measure of their potency as antigen presenting cells, fusion cells prominently stimulated allogeneic T cell proliferation in vitro. Mean stimulation indexes were 12, 57, and 31 for T cells stimulated by myeloma cells, DCs, and fusion cells, respectively. Adverse events judged to be potentially vaccine related included injection site reactions, pruritis, myalgias, fever, chills, and tachycardia. Six patients have completed the follow up period and 3 patients are currently undergoing vaccination. All patients achieved a partial response to transplant. Three patients demonstrated resolution of post-transplant paraprotein levels following vaccination. One patient with highly aggressive disease who experienced disease progression in the early post-transplant period, demonstrated initial response and then stabilization of disease with vaccination. We are examining the effect of transplant and vaccination on measures of cellular immunity, anti-tumor immunity and levels or activated as compared to regulatory T cells. T cell response to PHA mitogen was transiently depressed post-transplant. In contrast, a transient increase was noted post-transplant in mean T cell expression of IFNγ in response to autologous myeloma cell lysate. In preliminary studies, a relative increase in the ratio of activated (CD4/CD25low) to regulatory (CD4/CD25high) T cells was observed. To date, all evaluable patients demonstrated evidence of vaccine stimulated anti-tumor immunity as manifested by a rise in IFNγ expression by CD4 and/or CD8+ T cells following ex vivo exposure to autologous tumor lysate. In this ongoing study, fusion cell vaccination in conjunction with stem cell transplantation has been well tolerated, induced anti-tumor immunity and clinical responses in patients with multiple myeloma.

scholarly journals Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients

2005 ◽  
Vol 201 (5) ◽  
pp. 805-816 ◽  
Author(s):  
Paolo A. Muraro ◽  
Daniel C. Douek ◽  
Amy Packer ◽  
Katherine Chung ◽  
Francisco J. Guenaga ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Multiple Sclerosis Patients

Clinical trials have indicated that autologous hematopoietic stem cell transplantation (HSCT) can persistently suppress inflammatory disease activity in a subset of patients with severe multiple sclerosis (MS), but the mechanism has remained unclear. To understand whether the beneficial effects on the course of disease are mediated by lympho-depletive effects alone or are sustained by a regeneration of the immune repertoire, we examined the long-term immune reconstitution in patients with MS who received HSCT. After numeric recovery of leukocytes, at 2-yr follow-up there was on average a doubling of the frequency of naive CD4+ T cells at the expense of memory T cells. Phenotypic and T cell receptor excision circle (TREC) analysis confirmed a recent thymic origin of the expanded naive T cell subset. Analysis of the T cell receptor repertoire showed the reconstitution of an overall broader clonal diversity and an extensive renewal of clonal specificities compared with pretherapy. These data are the first to demonstrate that long-term suppression of inflammatory activity in MS patients who received HSCT does not depend on persisting lymphopenia and is associated with profound qualitative immunological changes that demonstrate a de novo regeneration of the T cell compartment.

scholarly journals Alpha/Beta T-Cell Depleted Grafts as an Immunological Booster to Treat Graft Failure after Hematopoietic Stem Cell Transplantation with HLA-Matched Related and Unrelated Donors

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
E. Rådestad ◽  
H. Wikell ◽  
M. Engström ◽  
E. Watz ◽  
B. Sundberg ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hematopoietic Stem ◽  
Unrelated Donors

Allogeneic hematopoietic stem cell transplantation is associated with several complications and risk factors, for example, graft versus host disease (GVHD), viral infections, relapse, and graft rejection. While high levels of CD3+ cells in grafts can contribute to GVHD, they also promote the graft versus leukemia (GVL) effect. Infusions of extra lymphocytes from the original stem cell donor can be used as a treatment after transplantation for relapse or poor immune reconstitution but also they increase the risk for GVHD. In peripheral blood, 95% of T-cells express theαβT-cell receptor and the remaining T-cells express theγδT-cell receptor. AsαβT-cells are the primary mediators of GVHD, depleting them from the graft should reduce this risk. In this pilot study, five patients transplanted with HLA-matched related and unrelated donors were treated withαβT-cell depleted stem cell boosts. The majority ofγδT-cells in the grafts expressedVδ2and/orVγ9. Most patients receivingαβ-depleted stem cell boosts increased their levels of white blood cells, platelets, and/or granulocytes 30 days after infusion. No signs of GVHD or other side effects were detected. A larger pool of patients with longer follow-up time is needed to confirm the data in this study.

T-cell receptor excision circle and T-cell dynamics after allogeneic stem cell transplantation are related to clinical events

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3449-3453 ◽  
Author(s):  
Mette D. Hazenberg ◽  
Sigrid A. Otto ◽  
Elmar S. de Pauw ◽  
Helene Roelofs ◽  
Willem E. Fibbe ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Cell Division ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Cell Receptor ◽  
Clinical Events

Abstract It is generally believed that homeostatic responses regulate T-cell recovery after peripheral stem cell transplantation (PSCT). We studied in detail immune recovery in relation to T-cell depletion and clinical events in a group of adult patients who underwent PSCT because of hematologic malignancies. Initially, significantly increased proportions of dividing naive, memory, and effector CD4+and CD8+ T cells were found that readily declined, despite still very low numbers of CD4+ and CD8+ T cells. After PSCT, increased T-cell division rates reflected immune activation because they were associated with episodes of infectious disease and graft-versus-host disease (GVHD). T-cell receptor excision circles (TRECs) were measured to monitor thymic output of naive T cells. Mean TREC content normalized rapidly after PSCT, long before naive T-cell numbers had significantly recovered. This is compatible with the continuous thymic production of TREC+ naive T cells and does not reflect homeostatic increases of thymic output. TREC content was decreased in patients with GVHD and infectious complications, which may be explained by the dilution of TRECs resulting from increased proliferation. Combining TREC and Ki67 analysis with repopulation kinetics led to the novel insight that recovery of TREC content and increased T-cell division during immune reconstitution after transplantation are related to clinical events rather than to homeostatic adaptation to T-cell depletion.

New Developments in Allotransplant Immunology

Hematology ◽  
2003 ◽  
Vol 2003 (1) ◽  
pp. 350-371 ◽  
Author(s):  
A. John Barrett ◽  
Katayoun Rezvani ◽  
Scott Solomon ◽  
Anne M. Dickinson ◽  
Xiao N. Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Immune Reconstitution ◽  
Cytokine Gene ◽  
Post Transplant ◽  
Cytokine Milieu ◽  
Cytokine Gene Polymorphisms

Abstract After allogeneic stem cell transplantation, the establishment of the donor’s immune system in an antigenically distinct recipient confers a therapeutic graft-versus-malignancy effect, but also causes graft-versus-host disease (GVHD) and protracted immune dysfunction. In the last decade, a molecular-level description of alloimmune interactions and the process of immune recovery leading to tolerance has emerged. Here, new developments in understanding alloresponses, genetic factors that modify them, and strategies to control immune reconstitution are described. In Section I, Dr. John Barrett and colleagues describe the cellular and molecular basis of the alloresponse and the mechanisms underlying the three major outcomes of engraftment, GVHD and the graft-versus-leukemia (GVL) effect. Increasing knowledge of leukemia-restricted antigens suggests ways to separate GVHD and GVL. Recent findings highlight a central role of hematopoietic-derived antigen-presenting cells in the initiation of GVHD and distinct properties of natural killer (NK) cell alloreactivity in engraftment and GVL that are of therapeutic importance. Finally, a detailed map of cellular immune recovery post-transplant is emerging which highlights the importance of post-thymic lymphocytes in determining outcome in the critical first few months following stem cell transplantation. Factors that modify immune reconstitution include immunosuppression, GVHD, the cytokine milieu and poorly-defined homeostatic mechanisms which encourage irregular T cell expansions driven by immunodominant T cell–antigen interactions. In Section II, Prof. Anne Dickinson and colleagues describe genetic polymorphisms outside the human leukocyte antigen (HLA) system that determine the nature of immune reconstitution after allogeneic stem cell transplantation (SCT) and thereby affect transplant outcomethrough GVHD, GVL, and transplant-related mortality. Polymorphisms in cytokine gene promotors and other less characterized genes affect the cytokine milieu of the recipient and the immune reactivity of the donor. Some cytokine gene polymorphisms are significantly associated with transplant outcome. Other non-HLA genes strongly affecting alloresponses code for minor histocompatibility antigens (mHA). Differences between donor and recipient mHA cause GVHD or GVL reactions or graft rejection. Both cytokine gene polymorphisms (CGP) and mHA differences resulting on donor-recipient incompatibilities can be jointly assessed in the skin explant assay as a functional way to select the most suitable donor or the best transplant approach for the recipient. In Section III, Dr. Nelson Chao describes non-pharmaceutical techniques to control immune reconstitution post-transplant. T cells stimulated by host alloantigens can be distinguished from resting T cells by the expression of a variety of activation markers (IL-2 receptor, FAS, CD69, CD71) and by an increased photosensitivity to rhodamine dyes. These differences form the basis for eliminating GVHD-reactive T cells in vitro while conserving GVL and anti-viral immunity. Other attempts to control immune reactions post-transplant include the insertion of suicide genes into the transplanted T cells for effective termination of GVHD reactions, the removal of CD62 ligand expressing cells, and the modulation of T cell reactivity by favoring Th2, Tc2 lymphocyte subset expansion. These technologies could eliminate GVHD while preserving T cell responses to leukemia and reactivating viruses.

scholarly journals T-cell receptor-α repertoire of CD8+ T cells following allogeneic stem cell transplantation using next-generation sequencing

Haematologica ◽  
2018 ◽  
Vol 104 (3) ◽  
pp. 622-631 ◽  
Author(s):  
Cornelia S. Link-Rachner ◽  
Anne Eugster ◽  
Elke Rücker-Braun ◽  
Falk Heidenreich ◽  
Uta Oelschlägel ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Next Generation Sequencing ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Allogeneic Stem Cell Transplantation ◽  
Cell Receptor ◽  
Generation Sequencing

scholarly journals Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation

Leukemia ◽  
2019 ◽  
Vol 34 (5) ◽  
pp. 1422-1432 ◽  
Author(s):  
Stéphane Buhler ◽  
Florence Bettens ◽  
Carole Dantin ◽  
Sylvie Ferrari-Lacraz ◽  
Marc Ansari ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hematopoietic Stem

Prediction of T-cell reconstitution by assessment of T-cell receptor excision circle before allogeneic hematopoietic stem cell transplantation in pediatric patients

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 886-893 ◽  
Author(s):  
Xiaohua Chen ◽  
Raymond Barfield ◽  
Ely Benaim ◽  
Wing Leung ◽  
James Knowles ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Hematopoietic Stem ◽  
Thymic Function ◽  
T Cell Reconstitution

Abstract The extent and rapidity with which T cells are regenerated from graft-derived precursor cells directly influences the incidence of infection and the T-cell–based graft-versus-tumor effect. Measurement of T-cell receptor excision circles (TRECs) in peripheral blood is a means of quantifying recent thymic T-cell production and has been used after transplantation in many studies to estimate thymus-dependent T-cell reconstitution. We hypothesized that the quality of thymic function before transplantation affects thymus-dependent T-cell reconstitution after transplantation. We used real-time polymerase chain reaction (PCR) to quantify signal-joint TRECs (sjTRECs) before and after transplantation. T-cell reconstitution was evaluated by T-cell receptor β (TCRβ) CDR3 size spectratyping. We tested 77 healthy sibling donors and 244 samples from 26 pediatric recipients of allogeneic hematopoietic stem cell transplantation (AHSCT). Blood from the healthy donors contained 1200 to 155 000 sjTREC copies/mL blood. Patients who had greater than 1200 copies/mL blood before transplantation showed early recovery of sjTREC numbers and TCRβ repertoire diversity. In contrast, patients who had fewer than 1200 copies/mL blood before transplantation demonstrated significantly slower restoration of thymus-dependent T cells. We conclude that the rate of reconstitution of thymus-dependent T cells is dependent on the competence of thymic function in the recipients before transplantation. Therefore, pretransplantation measurement of sjTREC may provide an important tool for predicting thymus-dependent T-cell reconstitution after transplantation.

Reconstitution of Memory T -Cells after Allogeneic Stem Cell Transplantation in Patients with Post-Transplantation Cyclophosphamide As Tolerance Induction

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5475-5475
Author(s):  
Vera Vasilyeva ◽  
Elena N. Parovichnikova ◽  
Larisa A. Kuzmina ◽  
Mikhail Drokov ◽  
Ekaterina Mikhaltsova ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Memory T Cells ◽  
Becton Dickinson ◽  
Post Transplantation ◽  
Post Transplant

Abstract Introduction. Nowadays high-dose post-transplantation cyclophosphamide (CY) replace standard immunosuppression (IST). Thereby, the investigation of T-cells reconstitution after post-transplant-CY doesn't reach appropriate level, and probably it's very different from what we see after standard IST. We studied the reconstitution of memory T-cells on day of engraftment (WBC>1000 cells\us) after allogenic hematopoietic stem cell transplantation (allo-HSCT) with post-transplant-CY and standard immunosuppression therapy. Patients and methods. During 2 years, 29 patients with different hematological malignancies were included in this study. Median of age was 36 years (24-60 years). 16 patients were males, 13 - females. 22 received RIC, 7 - myeloablative regime. Match unrelated donor (MUD) was in 17 cases, "Mismatch" MUD - 2, Match related donor (MRD) - 9, "Mismatch"MRD - 1. 4 patients were in relapse or disease progression. CY as alternative IST was administrated to 6 patients. Standard immunosuppression consisted of CSA, MMF or MTX at standard dose. Peripheral blood samples were collected in EDTA-tubes at day of engraftment after allo-HSCT (Me= 20 day (14-35)). Isolation of mononuclear cells from human peripheral blood was made by standard protocol using Lympholyte®-M Cell Separation Media (Cedarlane Labs). The anti-CD4- APC-Cy7 antibody (Becton Dickinson, USA) and FSC/SSC were used for determine population of CD4+T-cells. Anti-CD45R0- FITC (Becton Dickinson, USA) antibody were used to determine memory T-cells as subpopulation of CD4+ T-cells. Due to cyto- and lymphopenia 1,000,000 events was analyzed. Results. Mann-Whitney U test was used to test for differences between memory T-cells (CD4+ CD45R0+) after post-transplant-CY alone and in a group with standard IST. The percent of memory T-cells in CD4+ cell population at day of engraftment after post-transplant CY alone was statistically higher (74,3% ± 5,1% ,p=0.048*) than in patients with standard immunosuppression (49,4%±6,7%). Conclusion. We may conclude that patients with post-transplant CY had a different "T cell reconstitution profile". Reported data show us that probably post-transplant CY spares memory T-cells in contrast with standard IST, and also probably that CY is more selectively immunosuppressor than "gold standard" (such as CSA, MMF and etc.) not only on effector T-cells population. Despite the fact that the analyzed group is small, obtained data is important and needs further investigation. Disclosures No relevant conflicts of interest to declare.

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