History of haematopoietic stem-cell transplantation

Abstract

After fifty years of investigations into the use of pluripotent haematopoietic stem-cell transplantation for cancer therapy, this procedure has progressed from one that was thought to be plagued with insurmountable complications to a standard treatment for many haematological malignancies. How have these hurdles been overcome, and how can the therapy be expanded to include patients who are too old or medically infirm to tolerate conventional transplant approaches?

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Figure 1: Nobel prize for stem-cell transplantation.
Figure 2: Non-myeloablative approaches to bone-marrow transplantation.

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DATABASES

CancerNet:

acute lymphoblastic leukaemia

breast cancer

chronic myelogenous leukaemia

colon cancer

Hodgkin's disease

pancreatic cancer

prostate cancer

 Medscape DrugInfo:

busulphan

cyclophosphamide

cyclosporine

methotrexate

tacrolimus

FURTHER INFORMATION

American Cancer Society web site

American Society of Cancer Oncology Online

American Society of Hematology web site

Bone Marrow Donors Worldwide (BMDW)

BMDW article

Cancer.gov

Fred Hutchinson Cancer Research Center

International Bone Marrow Transplant Registry

Seattle Cancer Care Alliance

World Marrow Donor Association

Glossary

ALLOGRAFT

The transfer of haematopoietic cells that are anti-genically distinct or genetically different from one member of a species to another individual of the same species (such as from sister to brother or from an unrelated donor to a recipient).

ANERGY

A T-cell state of unresponsiveness, in which they cannot be activated by antigen.

AUTOLOGOUS TRANSPLANT

The removal, storage and re-infusion of a patient's own haematopoietic stem cells.

BONE-MARROW APLASIA

Lack of cellular development in the bone marrow.

CD34+ CELLS

The CD34+ compartment constitutes a heterogeneous population of haematopoietic cells (approximately 1–4% of nucleated marrow and 0.1–0.2%of peripheral blood cells), which not only includes more committed lineage-restricted progenitors, but also primitive uncommitted progenitors that are capable of initiating long-term reconstitution of haematopoiesis.

GRAFT-VERSUS-HOST DISEASE

A toxic reaction that is mediated by donor-derived T lymphocytes within the graft towards the recipient's organs. The attack is usually directed toward the skin, gut, liver and haematopoietic cells.

GRAFT-VERSUS-TUMOUR EFFECT

Killing of cancer cells that is mediated by the transplanted T lymphocyte cells or their progeny.

HAEMATOPOIETIC STEM CELL

A primitive and immature cell of the haematopoietic system that has the capacity to give rise to all the cells of the blood system, as well as the ability to self-renew. Allogeneic haematopoietic stem-cell transplantation involves the transfer of both immature and mature blood cells from the bone marrow, peripheral blood or cord blood from one individual to another.

HISTOCOMPATIBILITY

In the absence of immunosuppressive drugs, transplantation of haematopoietic cells between two dissimilar individuals universally results in an immune reaction that leads to graft rejection. This reactivity results from differences in cell-surface determinants, such as histocompatibility antigens between the transplant donor and the host. Histocompatibility is detemined by the presence of compatible human leukocyte antigens (HLA) that are present on the surface of cells.

MINOR HISTOCOMPATIBILITY ANTIGENS

Cellular proteins encoded by polymorphic genes that are differentially expressed on haematopoietic cells.

MIXED CHIMERISM

The presence of blood cells of both donor and host in origin within the recipient of the haematopoietic stem-cell transplant. Chimerism is operationally defined as the presence of 2.5–97.5% cells of donor or host origin, as dictated by the sensitivity of the assay that is used to detect chimerism.

NON-ABLATIVE

(Or non-myeloablative). Minimally bone-marrow suppressive.

SYNGENEIC TRANSPLANT

Transfer of haematopoietic cells between individuals who have identical genotypes (such as twins).

TOTAL BODY IRRADIATION

(TBI). Exposure of the entire body to radiant energy (external beam γ-irradiation) for therapeutic purposes.

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Little, MT., Storb, R. History of haematopoietic stem-cell transplantation. Nat Rev Cancer 2, 231–238 (2002). https://doi.org/10.1038/nrc748

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