Abstract. Adjuvant transfusion of donor lymphocytes (aDLT) may reduce the risk of relapse after allogeneic stem cell transplantation. We report our data on aDLT
Lymphocyte transfusion therapy, which I explained thoroughly to Dr. Oz, has been drowned out of public ears by the media circus. Cancer and AIDS (among others) are diseases of immune deficiency. I asked Professor Terasaki of UCLA in the early 1990s to obtain legal permission to treat cancer patients with immune transfusions from young, selected individuals. This lymphocyte transfusion can be legally done today in ANY of your hospitals and resulted in many remissions years ago. This was published by UCLA but never brought to the public.. Paul Terasaki took blood from the children of parents with cancer and the immune system of the children destroyed their parents cancer. Every case went into a temporary remission. It was not permanent because several transfusions were needed- three to six at least and only one was done. Terasaki ignored the cancers return and the childrens tears as they begged to be allowed to give another transfusion to the parents, saying that he had already proven his ...
Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ (2005) Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 23(24):5675-5687. https://doi.org/10.1200/JCO.2005.07.061 CrossRefPubMedGoogle Scholar ...
Successful prevention of post-transplantation relapse after donor lymphocyte infusion (DLI) depends on its capability to mediate an effective graft-versus-leukemia (GVL) response while minimizing DLI-related toxicity, including graft-versus-host disease (GVHD). We assessed the effects of decitabine (DEC), a hypomethylating agent, upon allogeneic immune reaction in a murine model of DLI. Significantly greater tumor growth retardation and survival prolongation occurred in mice administered with 1.0 mg/kg DEC for 5 days (DEC-1.0) than in control or DEC-0.1 mice. Upon prompt DEC and DLI co-administration, dendritic cells (DCs) were activated; DEC-1.0/DLI induced severe GVHD, and survival was significantly lower than with DLI alone or DEC-0.1/DLI treatments. IFN-γ and CD28 levels were higher in splenic DCs of DEC-1.0 mice than in those of control mice. Assessment of delayed DLI co-administration with DEC, when IFN-γ levels were normalized to control levels, revealed that DEC-1.0/DLI successfully
Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication of T-lymphocyte deplete allogeneic hematopoietic stem cell transplantation (allo-HSCT). For patients with PTLD refractory to Rituximab, donor lymphocyte infusion (DLI) is established as a successful option for salvage therapy. However, although in vivo lymphocyte expansion has been correlated with good clinical outcome following DLI, the specificity and functional characteristics of EBV-specific T-cell responses remain poorly characterized. Here we describe two patients with Rituximab-refractory PTLD complicating T-cell deplete allo-HSCT, both of whom were successfully rescued with 1 × 106/Kg unselected stem cell donor-derived DLI. Prospective analyses revealed that complete clinical and radiological responses were associated with in vivo expansion of T and NK cells. Furthermore, EBV MHC tetramer, and interferon gamma analyses revealed a marked increase in EBV-specific T-cell
Having a donor lymphocyte infusion (DLI) means youll get more cells from your original donor. It aims to push your chimerism levels up towards 100%.
Donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukaemia.: The understanding of the use of d
Abstract. Introduction: Early response rates to non-myeloablative therapy are encouraging, however long term remissions remain elusive. Manipulating donor lymp
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TY - JOUR. T1 - Induction of Immune Response after Allogeneic Wilms Tumor 1 Dendritic Cell Vaccination and Donor Lymphocyte Infusion in Patients with Hematologic Malignancies and Post-Transplantation Relapse. AU - Shah, Nirali N.. AU - Loeb, David M.. AU - Khuu, Hahn. AU - Stroncek, David. AU - Ariyo, Tolu. AU - Raffeld, Mark. AU - Delbrook, Cindy. AU - Mackall, Crystal L.. AU - Wayne, Alan S.. AU - Fry, Terry J.. N1 - Funding Information: We gratefully acknowledge the study participants and their families, referring medical care teams, and the faculty and staff of the National Institutes of Health. This research was supported by the Intramural Research Program of the NIH , Center for Cancer Research , National Cancer Institute . Publisher Copyright: © 2016. PY - 2016/12/1. Y1 - 2016/12/1. N2 - Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). Treatment for post-HCT relapse using donor lymphocyte ...
RATIONALE: Giving an infusion of donor lymphocytes may be able to kill cancer cells in patients with hematologic cancer that has come back after a donor stem cell transplant.. PURPOSE: This clinical trial is studying how well donor lymphocyte infusion works in treating patients with recurrent or persistent hematologic cancer after donor stem cell transplant. ...
Cryopreserved donor lymphocyte infusion (DLI) products are manufactured and administered to treat relapse after allogeneic hematopoietic stem cell transplantation. Reported clinical responses to DLIs vary broadly, even within the same group of patients. While there is an implicit recognition of the fact that different manufacturing protocols may have specific effects on different cell types, cryopreservation protocols are frequently derived from our experience in the cryopreservation of stem cell products and do not account for the heterogeneous functional nature of DLI T-cell populations. Here, we report the results of a prospective, multicenter trial on the effect of four different cryopreservation solutions that were used to freeze DLIs compared to control DLIs that were refrigerated overnight ...
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followed by donor lymphocyte infusion (DLI) from HLA -haploidentical donors is a safe procedure that will not cause Graft ... (consolidation) at 1.0 g/m2 for 6 dosages followed by HLA-mismatched DLI after the second consolidation. Biological: DLI HLA-mismatched DLI will be administered Day 9, approximately 24-48 hours .... Clinical Trial last updated 05/03/2016 - 9:59am.. ...
GET 2020. Convalescent donor SARS-COV-2-specific cytotoxic T lymphocyte infusion as a possible treatment option for COVID-19 patients with severe disease has not received enough attention till date Extract ...
Liu Hong-tao,Liu Dai-hong,Huang Xiao-jun,et al. Treatments of disease relapse after allogeneic stem cell transplantation focusing on donor lymphocyte infusion[J]. CHINESE MEDICAL JOURNAL,2013,126(22):4380-4388 ...
Patients with leukemia who receive a T cell-depleted allogeneic stem cell graft followed by postponed donor lymphocyte infusion (DLI) can experience graft-versus-leukemia (GVL) reactivity, with a lower risk of graft-versus-host disease (GVHD). Here, we have investigated the magnitude, diversity, and specificity of alloreactive CD8 T cells in patients who developed GVL reactivity after DLI in the absence or presence of GVHD. We observed a lower magnitude and diversity of CD8 T cells for minor histocompatibility antigens (MiHAs) in patients with selective GVL reactivity without GVHD. Furthermore, we demonstrated that MiHA-specific T cell clones from patients with selective GVL reactivity showed lower reactivity against nonhematopoietic cells, even when pretreated with inflammatory cytokines. Expression analysis of MiHA-encoding genes showed that similar types of antigens were recognized in both patient groups, but in patients who developed GVHD, T cell reactivity was skewed to target broadly ...
CT-011 mAb. CT-011 has been produced and provided for this clinical trial by CureTech Ltd.. Patient selection. Entrance criteria for the study required that patients enrolled in the study had to have one of the following hematologic malignancies: acute myeloid leukemia (AML), chronic lymphocytic leukemia, non-Hodgkins lymphoma, Hodgkins lymphoma, or multiple myeloma at an advanced stage of their disease and following chemotherapy and/or stem cell transplantation. Patients were eligible for this study provided that they met the following criteria: age 18 to 65 y; measurable disease (blast count and morphology, computed tomography scan or protein electrophoresis, β2 microglobulin, immunoelectrophoresis, Bence Jones protein in urine); at least 4 wk from stem cell transplantation or 1 wk from donor lymphocyte infusion; Eastern Oncology Cooperative Group (ECOG) performance score ,2; life expectancy ,3 mo; hematology: WBC ,0.5 × 109/L, hemoglobin ,7 g/dL, and platelet count ,10 × 109/L; adequate ...
Loss of chimerism is one of the major problems after allogeneic stem cell transplantation(SCT). Donor- lymphocyte infusions(DLI) are used as a treatment after taper or stopping immunosuppression. In this study, DLI ...
The Immunodeficiency of Bone Marrow-Transplanted Patients: The Effect of Patient Lymphocytes on the Response of Donor Lymphocytes to Mitogens and Allogeneic Cells ...
平成23年4月 岡山大学病院講師(輸血部). 【一言】丁寧で安定感のある診療を心がけています。. 【研究テーマ】移植後肺合併症、ドナーリンパ球輸注によるGVL効果. 【主な業績】. ● Nishie M , Fujii N, Mimura Y , Asano T, Mimura-Kimura Y, Aoe K, Aoe M, Nakashima H, Fujiwara H, Nishimori H, Matsuoka KI, Kondo E, Maeda Y, Tanimoto M. Vigorous inflammatory responses in non-infectious pulmonary complication induced by donor lymphocyte infusion. Transfusion. 2015 (in press). ● Asano T, Fujii N, Niiya D, Nishimori H, Fujii K, Matsuoka K, Ichimura K, Hamada T, Kondo E, Maeda Y, Tanimoto Y, Shinagawa K, Tanimoto M. Complete resolution of steroid-resistant organizing pneumonia associated with myelodysplastic syndrome following allogeneic hematopoietic cell transplantation. Springerplus. 2014 Jan 2;3:3. ● Fujii N, Nakase K, Asakura S, Matsuo K, Nawa Y, Sunami K, Nishimori H, Matsuoka K, Kondo E, Maeda Y, Shinagawa K, Hara M, Tanimoto M ...
For patients suffering from blood cancers, an allogeneic hematopoietic stem cell transplantation (HSCT) is generally regarded as the most effective curative approach. During an HSCT treatment, the bone marrow, harboring the diseased cancer cells, is completely destroyed and subsequently replaced by stem cells in the graft from a healthy donor. After an HSCT treatment it usually takes the patient at least six to twelve months to recover to near-normal blood cell levels and immune cell functions. During this period, the patient is highly vulnerable to infections caused by bacteria, viruses and fungi but also to disease relapse.. ATIR101™ (Allodepleted T-cell ImmunotheRapeutics) provides for a safe donor lymphocyte infusion (DLI) from a partially matched (haploidentical) family member without the risk of causing severe Graft-versus-Host-Disease (GVHD). The T-cells in ATIR101™ will help fight infections and remaining tumor cells and thereby bridge the time until the immune system has fully ...
Purpose: We hypothesized that lymphoid-selective host conditioning and subsequent adoptive transfer of sirolimus-resistant allogeneic T cells (T-Rapa), when combined with high-dose sirolimus drug therapy in vivo, would safely achieve antitumor effects while avoiding GVHD.. Experimental Design: Patients (n = 10) with metastatic renal cell carcinoma (RCC) were accrued because this disease is relatively refractory to high-dose conditioning yet may respond to high-dose sirolimus. A 21-day outpatient regimen of weekly pentostatin (P; 4 mg/m2/dose) combined with daily, dose-adjusted cyclophosphamide (C; ≤200 mg/d) was designed to deplete and suppress host T cells. After PC conditioning, patients received matched sibling, T-cell-replete peripheral blood stem cell allografts, and high-dose sirolimus (serum trough target, 20-30 ng/mL). To augment graft-versus-tumor (GVT) effects, multiple T-Rapa donor lymphocyte infusions (DLI) were administered (days 0, 14, and 45 posttransplant), and sirolimus was ...
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These experiments explored mechanisms of control of acute lymphoblastic leukemia following allogeneic hematopoietic stem cell transplantation using a murine model of MHC-matched, minor histocompatibility antigen mismatched transplantation. The central hypothesis examined was that addition of active vaccination against leukemia cells would substantially increase the effectiveness of allogeneic donor lymphocyte infusion against ALL present in the host after transplant. While vaccination did increase the magnitude of type I T cell responses against leukemia cells associated with donor lymphocyte infusion, it did not lead to substantial improvement in long term survival. Analysis of immunological mechanisms of leukemia progression demonstrated that the failure of vaccination was not due to antigen loss in leukemia cells. However, analysis of survival provided surprising findings that, in addition to very modest type I T cell responses, a B cell response that produced antibodies that bind leukemia ...
Currently each application is processed independently with bilateral agreements; formal data acquisition policies, service-level agreements (SLAs), and data provider registration procedures will be produced at a later stage.. In parallel to the systems development the PDS-WG is also starting to consider a broader framework of standards, quality, and coordination.. Based on feedback from content providers and consumers, PDS-WG will continue to refine the DLI service data model and exchange format to make it a universal, cross-platform, cross-discipline solution for collecting and sharing dataset-literature links.. How would you use the DLI service? To inform optimization of the query and access interfaces, further detail is now sought on end-user scenarios. ...
Zaleski, M, Effect of host-versus-graft and graft-versus-host reactions on the immune response of mice to sheep red blood cells. (1971). Subject Strain Bibliography 1971. 764 ...
Fondazione IRCCS Istituto Nazionale Tumori di Milano. Methods to provide safer stem cell transplants to individuals who are not completely compatible with the donor are being developed. Encouraging results have come from a post-transplant cellular therapy, which strengthens the immune system against viral infections and tumors, developed for the first time at the National Tumor Institute (INT) in Milan. The INT conducted the first phase I-II study in the world, published in Blood, whose main objective was to assess the use of a low dose radiochemotherapy, followed by low dose post-transplant infusions CD8-depleted donor lymphocytes after ...
A simple questionnaire that rates breathing difficulties on a scale of 0 to 3 predicts survival in chronic graft-vs.-host disease (GVHD), according to a current study.
A Phase II, Open-label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Allogeneic Stem Cell Transplant
TY - JOUR. T1 - Characterization of Cord Blood Natural Killer and Lymphokine Activated Killer Lymphocytes Following Ex Vivo Cellular Engineering. AU - Ayello, Janet. AU - van de Ven, Carmella. AU - Fortino, Weiwei. AU - Wade-Harris, Cheryl. AU - Satwani, Prakash. AU - Baxi, Laxmi. AU - Simpson, Lynn L.. AU - Sanger, Warren G. AU - Pickering, Diana. AU - Kurtzberg, Joanne. AU - Cairo, Mitchell S.. PY - 2006/6/1. Y1 - 2006/6/1. N2 - Cord blood (CB) natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic cells are poorly characterized but might be used to treat minimal residual and/or recurrent malignant disease. Currently, there is no mechanism to use CB for adoptive cancer cellular immunotherapy after CB transplantation (CBT). Recognizing this as a deficiency, we hypothesized that CB aliquots could be engineered ex vivo for potential donor lymphocyte infusion after CBT. Cryopreserved CB aliquots were thawed, depleted of monocytes, and cultured in serum-free medium alone or serum-free ...
In this study, we have reported that type I IFNs induce a rapid differentiation of freshly isolated GM-CSF-treated human monocytes into short-lived DCs endowed with potent functional activities both in vitro and in vivo, using the hu-PBL-SCID mouse model. The comparison of DCs generated in the presence of IFN/GM-CSF with those obtained after the standard IL-4/GM-CSF treatment revealed that type I IFN was definitively superior in inducing a rapid and stable differentiation process and in conferring to DCs a full functional activity to trigger a potent primary human immune response both in vitro and in hu-PBL-SCID mice. In particular, IFN induced an early detachment of monocytes from culture plates, paralleled by rapid acquisition of high levels of CD40, CD54, CD80, CD86, and HLA-DR molecules within 3 d, whereas IL-4/GM-CSF-treated monocytes required at least 6 d to fully acquire the immature DC phenotype. Of interest, a remarkable percentage of CD83-expressing DCs was observed in IFN-treated ...
Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells. In the 1960s, lymphocytes were discovered to be the mediators of allograft rejection in animals. Attempts to use T cells to treat transplanted murine tumors required cultivating and manipulating T cells in culture. Syngeneic lymphocytes were transferred from rodents heavily immunized against the tumor to inhibit growth of small established tumors, becoming the first example of ACT. Description of T cell growth factor interleukin-2 (IL-2) in 1976 ...
Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, but fatal complication of blood transfusions. TA-GVHD occurs when donor lymphocytes, not recognized as foreign antigen, mount an immune response against the recipients tissue. While host immune defects, component characteristics and donor-recipient HLA relationships have all been identified as factors associated with TA-GVHD, the relative importance of each […]. [Read More] ...
In this paper, five points are summarized: 1 What is a graft-versus-host disease (reaction). 2 When and why does it occur. 3 What is the spectrum of its cutaneous manifestations. 4 What is (are)...
Acronyms and Abbreviations: ALL, acute lymphatic leukemia; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; cDNA, complementary DNA; CDR3, complementarity determining region 3; CEA, carcinoembryonic antigen; CLL, chronic lymphatic leukemia; CMV, cytomegalovirus; CRS, cytokine release syndrome; CTL, cytotoxic T lymphocyte; DLI, donor lymphocyte infusion; E, early viral protein; EBV, Epstein-Barr virus; EGFR, epidermal growth factor receptor; ERBB2IP, erbb2 interacting protein; GD2, disialoganglioside; GVHD, graft-versus-host disease; GVL, graft-versus-leukemia; HHV-6, human herpes virus-6; HLA, human leukocyte antigen; HSCT, hematopoietic stem cell transplantation; HSV, herpes simplex virus; HSV-TK, herpes simplex virus thymidine kinase; iCasp9, inducible caspase-9; IE, immediate early viral protein; IFN-γ, interferon-γ; IL, interleukin; L1CAM, L1-cell adhesion molecule; LCL, lymphoblastoid cell line; LPD, lymphoproliferative disease; mAbs, monoclonal antibodies; mHAgs, minor ...
Graft-versus-tumor effect (GvT) appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T cells (T lymphocytes) that can be beneficial for the recipient by eliminating residual malignant cells. GvT might develop after recognizing tumor-specific or recipient-specific alloantigens.[99] It could lead to remission or immune control of hematologic malignancies. This effect applies in myeloma and lymphoid leukemias, lymphoma, multiple myeloma and possibly breast cancer. It is closely linked with graft-versus-host disease (GvHD), as the underlying principle of alloimmunity is the same. CD4+CD25+ regulatory T cells (Treg) can be used to suppress GvHD without loss of beneficial GvT effect. The biology of GvT response still isnt fully understood but it is probable that the reaction with polymorphic minor histocompatibility antigens expressed either specifically on hematopoietic cells or more widely on a number of tissue cells or tumor-associated antigens is ...