23rd July 2024

Haematopoietic stem cell transplant (HSCT)

Overview of HSCT

HSCT involves the harvest of multipotent haematopoietic stem cells (HSC) from a donor and infusion into a recipient. The aims are:

• To allow for haematopoietic reconstitution after myeloablative doses of chemo(radio)therapy
• To replace congenital or acquired abnormal bone marrow or immune function

HSC can be harvested from bone marrow, peripheral blood or umbilical cord blood.

Bone marrow samples are usually obtained from a donor’s posterior iliac crest under general anaesthetic.

Peripheral blood stem cells are harvested through apheresis following 4-5 days of daily injections with granulocyte colony-stimulating factor to ‘mobilise’ the stem cells.

Indications for HSCT include AML, ALL, CML, CLL, MDSs, myelofibrosis, various NHLs and HL. HSCT is also a clinical option or developmental in some solid tumour malignancies.

Classification of HSCT

HSCT can be autologous or allogeneic.

In autologous transplants, a patient’s own stem cells are harvested and transplanted back into the patient after high-dose chemo(radio)therapy.

In allogeneic transplants, HSCs are harvested from a donor and transplanted into the recipient patient. Recipients need to be HLA-matched to the donors to reduce risk of rejection and graft-versus-host disease (GvHD). HLA-matched related donors are preferred. If a matched related donor cannot be found, then matched unrelated donors are searched for. Minimally mismatched donors (related or unrelated) are sometimes tolerated if no other suitable donor is found.

Complications of HSCT

There are numerous complications that can occur after HSCT. Complications are considered early if they happen within one year of transplant and late if they occur after this.

Graft-versus-host disease

GvHD is a complication of allogeneic HSCT when donor T-lymphocytes respond to histoincompatible antigens on host tissue.

Higher degree of HLA-mismatch, older donor/recipient age and sex disparity all increase the risk of GvHD.

GvHD can be acute, chronic or exhibit an overlap syndrome. They are differentiated by clinical findings.

Prophylaxis is generally with ciclosporin/tacrolimus and methotrexate/mycophenolate mofetil. There can be complications from these medications, e.g. gingival hyperplasia with ciclosporin and renal failure with tacrolimus.

Acute GvHD

Classic acute GvHD occurs <100 days post-HSCT; if it occurs after this, it is classified as late onset acute GvHD.

• Skin: maculopapular rash on neck, ears, shoulders, palms and soles
• Gastrointestinal tract: can affect the upper and lower gastrointestinal tract causing nausea, vomiting, anorexia, diarrhoea and abdominal cramps
• Liver: damage to bile canaliculi causing cholestasis and elevated bilirubin and deranged liver function tests

Isolated skin acute GvHD affecting <50% of the skin is treated with topical treatments, including steroids.

Any other acute GvHD is treated with systemic oral steroids and ciclosporin/tacrolimus.

Chronic GvHD

Chronic GvHD normally occurs >3 months after HSCT but can occur at any time after it, even many years. If there are features of acute GvHD then it is an ‘overlap syndrome’.

It typically affects the skin, liver, gastrointestinal tract and lungs, but any organ system can be affected:

• Skin: erythema, plaques, desquamation, lichen planus-like, joint contractures, scleroderma-like
• Mouth: xerostomia, mucositis, gingivitis, ulcers
• Liver: acute hepatitis or slowly progressive cholestasis
• Gastrointestinal tract: can affect the upper and lower gastrointestinal tract causing nausea, vomiting, anorexia, diarrhoea, exocrine pancreatic insufficiency
• Lung: bronchiolitis obliterans causing dyspnoea on exertion, dry cough and decreased exercise tolerance
• Musculoskeletal: muscle cramps, arthralgia, arthritis

Mild disease may be managed by treatment localised to the system affected. Any other disease stage requires systemic steroids with adjunct therapy depending on the body system affected, e.g. emollients for skin and inhalers for lungs.

References

• Provan D, Baglin T, Dokal I, de Vos J. Oxford Handbook of Clinical Haematology. 4th ed. Oxford: Oxford University Press; 2015
• Negrin RS. Sources of hematopoietic stem cells [Internet]. Chao NJ, Rosmarin AG, editors. UpToDate. 2020 [cited 2022 Jan 10]. Available from: https://www.uptodate.com/contents/sources-of-hematopoietic-stem-cells
• Negrin RS. Donor selection for hematopoietic cell transplantation [Internet]. Chao NJ, Rosmarin AG, editors. UpToDate. 2021 [cited 2022 Jan 10]. Available from: https://www.uptodate.com/contents/donor-selection-for-hematopoietic-cell-transplantation
• Negrin RS. Early complications of hematopoietic cell transplantation [Internet]. Chao NJ, Rosmarin AG, editors. UpToDate. 2020 [cited 2022 Jan 10]. Available from: https://www.uptodate.com/contents/early-complications-of-hematopoietic-cell-transplantation
• Chao NJ. Survival, quality-of-life, and late complications after hematopoietic cell transplantation in adults [Internet]. Negrin RS, Rosmarin AG, editors. UpToDate. 2021 [cited 2022 Jan 10]. Available from: https://www.uptodate.com/contents/survival-quality-of-life-and-late-complications-after-hematopoietic-cell-transplantation-in-adults
• Chao NJ. Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease [Internet]. Negrin RS, Rosmarin AG, editors. UpToDate. 2021 [cited 2022 Jan 10]. Available from: https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-grading-of-acute-graft-versus-host-disease
• Zeiser R. Clinical manifestations and diagnosis of chronic graft-versus-host disease [Internet]. Negrin RS, Chao NJ, Rosmarin AG, editors. UpToDate. 2021 [cited 2022 Jan 10]. Available from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-graft-versus-host-disease
• Choi SW, Runaas L. Graft-versus-host disease [Internet]. BMJ Best Practice. 2021 [cited 2022 Jan 10]. Available from: https://bestpractice.bmj.com/topics/en-gb/946
• Chao NJ, Zeiser R. Treatment of acute graft-versus-host disease [Internet]. Negrin RS, Rosmarin AG, editors. UpToDate. 2021 [cited 2022 Jan 10]. Available from: https://www.uptodate.com/contents/treatment-of-acute-graft-versus-host-disease