Graft‐Vs.‐Tumor Responses

Fefer, A

doi:10.1002/9780470987070.ch28

Cited by 6 publications

(4 citation statements)

References 144 publications

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“…This beneficial graft-vs-leukemia (GvL) effect was first observed in a murine model of hematopoietic stem cell transplantation [1]. The GvL effect was next confirmed by the efficacy of donor lymphocyte injec-tion, first observed in patients with relapsed chronic myelogenous leukemia after allograft and showing a high rate of complete remission after treatment [2]. However, this alloreactivity is not restricted to tumor cells, because when directed against healthy recipient tissues, it is responsible for the clinical symptoms of graft-vs-host disease (GvHD), the main complication of allogeneic stem cell transplantation.…”

mentioning

confidence: 89%

Natural-killer cell amplification for adoptive leukemia relapse immunotherapy: Comparison of three cytokines, IL-2, IL-15, or IL-7 and impact on NKG2D, KIR2DL1, and KIR2DL2 expression

Decot

Voillard

Latger‐Cannard

et al. 2010

Experimental Hematology

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mentioning

confidence: 89%

Natural-killer cell amplification for adoptive leukemia relapse immunotherapy: Comparison of three cytokines, IL-2, IL-15, or IL-7 and impact on NKG2D, KIR2DL1, and KIR2DL2 expression

Decot

Voillard

Latger‐Cannard

et al. 2010

Experimental Hematology

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“…Because non‐tolerant donor T cells are critical for the induction of acute GvHD, this complication can be prevented by T‐cell depletion of the donor graft. However, this benefit of T‐cell depletion is offset by increased relapse rates (20) and an increased risk of graft rejection (21). Rejection can be prevented by more intensive host conditioning and increased HSC doses, even with extensively (one haplotype) HLA‐mismatched SC grafts, but at the expense of delayed immune reconstitution (22).…”

Section: Approaches To Separating Gvhd and Gvlmentioning

confidence: 99%

Manipulating the immune system for anti‐tumor responses and transplant tolerance via mixed hematopoietic chimerism

Gibbons

Sykes

2008

Immunological Reviews

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Stem cells (SCs) with varying potentiality have the capacity to repair injured tissues. While promising animal data have been obtained, allogeneic SCs and their progeny are subject to immune-mediated rejection. Here, we review the potential of hematopoietic stem cells (HSCs) to promote immune tolerance to allogeneic and xenogeneic organs and tissues, to reverse autoimmunity, and to be used optimally to cure hematologic malignancies. We also review the mechanisms by which hematopoietic cell transplantation (HCT) can promote anti-tumor responses and establish donor-specific transplantation tolerance. We discuss the barriers to clinical translation of animal studies and describe some recent studies indicating how they can be overcome. The recent achievements of durable mixed chimerism across human leukocyte antigen barriers without graft-versus-host disease and of organ allograft tolerance through combined kidney and bone marrow transplantation suggest that the potential of this approach for use in the treatment of many human diseases may ultimately be realized.

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“…Many retrospective studies have demonstrated inverse correlations between the occurrence or severity of acute or chronic GVHD and the risk of recurrent malignancy after HCT, and numerous reports have described the disappearance of malignant cells after donor lymphocyte infusion for treatment of recurrent malignancy after HCT. 16 The recent advent of nonmyeloablative conditioning regimens has further increased awareness of the important role played by donor T and NK cells in eliminating malignant cells in the recipient after HCT. 17 Many physicians are willing to accept some level of GVHD as necessary for optimal control of malignancy.…”

Section: Concern About Loss Of Graft-versus-malignancy (Gvm) Effectsmentioning

confidence: 99%

Study design and endpoints in graft-versus-host disease

Martin

2008

Best Practice & Research Clinical Haematology

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The design of clinical trials for prevention or treatment of acute or chronic graft-versus-host disease poses many challenges. These challenges include the selection of primary and secondary endpoints that demonstrate clinical benefit, and the identification of measures indicating success both for individual patients and groups. Assessment of response in treatment trials should ideally encompass the prior trajectory of change before treatment. The criteria, timing and duration of response should be specified, and the potential effects of concomitant treatment and complications other than GVHD should be taken into account in assessing outcomes. A crucial element in clinical trial design is the pre-specification of the hypothesis to be tested in quantitative terms. Potential barriers to enrollment should be carefully considered in order to ensure timely completion of the trial.

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Graft‐Vs.‐Tumor Responses

Cited by 6 publications

References 144 publications

Natural-killer cell amplification for adoptive leukemia relapse immunotherapy: Comparison of three cytokines, IL-2, IL-15, or IL-7 and impact on NKG2D, KIR2DL1, and KIR2DL2 expression

Natural-killer cell amplification for adoptive leukemia relapse immunotherapy: Comparison of three cytokines, IL-2, IL-15, or IL-7 and impact on NKG2D, KIR2DL1, and KIR2DL2 expression

Manipulating the immune system for anti‐tumor responses and transplant tolerance via mixed hematopoietic chimerism

Study design and endpoints in graft-versus-host disease

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