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Haemopoietic stem cell transplantation 

Haemopoietic stem cell transplantation

Haemopoietic stem cell transplantation

E.C. Gordon-Smith

and Emma Morris



Inclusion of additional data relating to the pathogenesis of GVHD.

Use of CXCR4 inhibitors for HSC mobilization.

Updated references.

Updated on 30 May 2013. The previous version of this content can be found here.
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date: 25 March 2017

Haemopoietic stem cells (HSC) give rise to the blood cell lineages and the cells of the immune system, and their transplantation may be an appropriate part of the management of conditions including (1) malignant haematological disorders e.g. leukaemia, lymphoma, myeloma (2) bone marrow failure syndromes—e.g. aplastic anaemia; (3) congenital disorders—(a) haematological—e.g. Fanconi’s anaemia; (b) immunological—severe combined immunodeficiency; (c) metabolic—e.g. lysosomal diseases.

Transplantation of HSC uses either autologous HSC (patient’s own stem cells) or allogeneic HSC (harvested from an appropriately matched sibling or unrelated healthy donor).

Successful engraftment of allogeneic haemopoietic stem cells into a patient depends upon (1) overcoming immune rejection by the recipient, and (2) preventing or suppressing graft-vs-host disease, in which donor cells mount an immune attack against recipient tissues.

Identification and sources of haemopoietic stem cells

Haemopoietic stem cells are principally identified by expression of the surface antigen CD34. Sources include (1) bone marrow; (2) peripheral blood—following stimulation by infusion into the donor of certain cytokines, e.g. granulocyte colony-stimulating factor (G-CSF); (3) umbilical cord blood.

Autologous haemopoietic stem cell transplantation (HSCT)

The rationale behind autologous HSCT is to facilitate the delivery of higher doses of chemotherapy than would otherwise be possible. As the patient’s haemopoietic stem cells are removed prior to transplant, cryopreserved, and stored, they can be re-infused following myeloablative chemotherapy. As the donor and recipient are the same individual, there is no immunological disparity and therefore no requirement for immune suppression or risk of graft vs. host disease, GVHD (see below).

However, as the harvested stem cells may be contaminated with undetectable malignant cells, there is a risk of relapse. The relapse risk depends on the underlying disease and response to pre-transplant chemo/radiotherapy. Studies attempting to purge the collected stem cells of contaminating malignant cells have been performed, but have failed to show any improvements in overall survival, relapse rate or disease-free survival compared to using unmanipulated stem cells.

Allogeneic HSCT

Selection of donors

Minor disparity between the HLA types of donor and recipient are allowable, but the greater the disparity the higher the frequency of complications. HLA-matched sibling donors are only available for about 1 in 3 recipients. For those without such a donor, possible sources are (1) volunteer donor banks, which can provide HLA-suitable matches for about 80% of recipients with the same genetic disequilibrium as the donor pool; (2) umbilical cord blood banks.

Conditioning regimen

Conditioning regimens include measures to induce immunosuppression (required for all allogeneic transplants, excepting those from identical twin donors) and, when appropriate, eradicate diseased bone marrow. They may be (1) myeloablative—cyclophosphamide with (a) total body irradiation (TBI), or (b) busulphan, or (c) antilymphocyte globulin (ALG); (2) nonmyeloablative—fludarabine with varying combinations of (a) ALG or alemtuzumab (anti-CD52), (b) low-dose cyclophosphamide or melphalan, (c) low-dose TBI. After transplantation, donor lymphocyte infusions may be given to patients with malignant disorders to enhance the graft-vs-leukaemia, GVL or graft-vs-tumour, GVT effect.

Graft-vs-host disease (GVHD)

Acute GVHD—this major cause of transplant-related morbidity and mortality may develop at any time within the first 6 weeks after transplantation. The clinico-pathological manifestions are secondary to the recognition of allo-antigens in receipient tissue, by donor-derived T lymphocytes, hence the importance of HLA typing. Manifestations involve (1) skin—maculopapular rash, generalized erythroderma, desquamation and bullae; (2) liver—severity graded according to level of serum bilirubin; and (3) gut—diarrhoea, persistent nausea, pain/ileus.

Chronic GVHD—may follow acute GVHD or emerge de novo several months after transplantation. Mainly affects the skin, but almost any organ may be affected, e.g. lung (broncheolitis obliterans), gut, liver, eyes (sicca syndrome), buccal mucosa, skin (sclerodermatous changes), and musculoskeletal system.

Prevention/treatment—these present a major challenge. Standard management is with ciclosporin, with or without methotrexate; alternative immunosuppressive agents include tacrolimus, sirolimus, rituximab (anti CD20), alemtuzumab (anti CD52), high-dose steroids, thalidomide.

Despite the additional morbidity (and mortality) associated with chronic GVHD, it is associated with a reduced risk of relapse, as donor T cells recognize tumour antigens in addition to recipient allo-antigens.

Other complications and prognosis

Conditioning regimens have considerable toxicity. (1) Acute—the patient is particularly vulnerable to infectious complications in a period of intense neutropenia, usually lasting 2 to 4 weeks after transplantation and lymphopenia, which may last some months. Patients are managed in isolation facilities, with (as appropriate) prophylactic measures against fungal infection, herpes simplex, Gram-negative bacterial infection and pneumocystis jiroveci. Prophylactic regimens vary according to local experience with resistant organisms and availability of newer antimicrobials. Broad-spectrum intravenous antimicrobial therapy is used to treat fevers empirically. Ganciclovir is given if routine monitoring shows evidence of cytomegalovirus reactivation. (2) Chronic—common manifestations include retardation of growth (particularly if transplanted in childhood), endocrine impairment, infertility, intellectual impairment (following cranial irradiation).

Prognosis—once the graft is fully established and tolerance is reconstituted, immunosuppression may be stopped. In the absence of GVHD, immune suppression can be weaned from as early as 3 months post-transplant. The procedure offers hope to many patients with life-threatening marrow failure or malignant disease for which no other treatment is available, but in the long term recipients have a reduced life expectancy due to relapse of the underlying disease, infection, and chronic graft-vs-host disease. There is an increased risk of solid tumours.

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