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Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer

An Erratum to this article was published on 03 March 2010

This article has been updated

Abstract

The year 2009 marked the fiftieth anniversary of the first successful allogeneic haematopoietic stem cell transplant (HSCT). The field of HSCT has pioneered some of the most exciting areas of research today. HSCT was the original stem cell therapy, the first cancer immune therapy and the earliest example of individualized cancer therapy. In this Timeline article we review the history of the development of HSCT and major advances made in the past 50 years. We highlight accomplishments made by researchers who continue to strive to improve outcomes for patients and increase the availability of this potentially life-saving therapy for patients with otherwise incurable malignancies.

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Figure 1: Pathophysiology of acute GVHD and GVT effects.
Figure 2: Treatment-related mortality and overall survival outcomes following allogeneic HSCT over different time periods.

Change history

  • 02 March 2010

    Figure 1 has been corrected in the HTML and PDF versions.

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Acknowledgements

The authors would like to acknowledge T. Pederson, V. He, M. Pasquini and M. Horwitz for the Center for International Blood and Marrow Transplant Research survival data presented, as well as M. Perales, J. Barker and J. Jurcic for critical comments on the manuscript.

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Glossary

Acute GVHD

Typically observed within the first 100 days post-transplant; can manifest in the skin, gastrointestinal tract, liver and haematopoietic system.

Allogeneic

From different individuals of the same species.

Antigen-presenting cells

Immune cells that present antigen to T cells, resulting in T cell priming and expansion.

Autologous

A graft from one's own self.

Chronic GVHD

Typically observed after day 100; can target many organ systems, including acute GVHD target organs as well as connective tissue and exocrine glands.

Donor leukocyte infusion

Infusion of peripheral blood white cells from a donor.

Double-unit cord blood transplant

Administering two cord blood units as the donor graft product for HSCT in adults.

Effector cells

Immune cells that can mediate the killing of other cells; includes CD8+ T cells, natural killer cells, macrophages and in certain circumstances CD4+ T cells.

Graft-versus-host disease (GVHD)

An immune-mediated, potentially life-threatening syndrome in which host tissues are attacked by donor immune cells. Clinically divided into acute and chronic forms.

Graft-versus-tumour (GVT) effect

A phenomenon in which malignant host cells are attacked by donor immune cells.

Immunosuppressive cell population

Immune cells, including regulatory T cells, natural killer T cells and myeloid suppressor cells, which suppress immune responses.

Killer immunoglobulin-like receptor

Receptor found on natural killer cells that can be activating or inhibitory.

Lymphopenia

Reduced numbers of lymphocytes, commonly following radiation or chemotherapy.

Minor histocompatability antigens

Polymorphisms in tissue-specific proteins resulting in histocompatibility antigens that can elicit allogeneic immune responses.

Mixed T cell chimerism

A situation following HSCT in which an individual has T cells of both donor and host origin.

Myeloablative

Causes bone marrow ablation owing to the loss of haematopoietic stem cells following high-dose radiation or chemotherapy.

Non-myeloablative conditioning

Doses of radiation and chemotherapy that immune suppress the host enough to allow engraftment of donor haematopoietic stem cells but that are not intense enough to completely ablate the host haematopoietic stem cells.

Sinusoidal obstruction syndrome (SOS)

A form of organ toxicity following high-dose therapy involving the obstruction of the hepatic sinusoids, resulting in increased bilirubin levels in the blood, abdominal pain and fluid retention.

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Jenq, R., van den Brink, M. Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer. Nat Rev Cancer 10, 213–221 (2010). https://doi.org/10.1038/nrc2804

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