Autologous stem cell transplantation

What is autologous stem cell transplantation?

Autologous stem cell transplantation is a procedure in which the patient’s stem cells are collected and are later injected back into the patient following chemotherapy or radiation therapy.

Autologous stem cell transplantation is used predominantly in haematological malignancies (lymphoma and leukaemia). It is sometimes used in autoimmune diseases including systemic lupus erythematosus, systemic sclerosis, and dermatomyositis, which have cutaneous manifestations.

Autologous stem cell transplantation is also known as autologous haematopoietic cell transplant and an autologous bone marrow transplant.

Who uses autologous stem cell transplantation?

Autologous stem cell transplantation enables higher doses of chemotherapy to be used than would be otherwise tolerated due to the toxicity of treatment on the bone marrow.

Autologous stem cell transplantation is well established in the treatment of various haematological malignancies with growing experience and use in solid tumours and autoimmune conditions.

Haematological malignancies

• Multiple myeloma and other plasma cell disorders — autologous stem cell transplantation is the standard of care in patients younger than 70 years. Myeloma was the indication for 46% of all autologous stem cell transplants in Europe in 2011.
• Non-Hodgkin and Hodgkin lymphoma. Lymphoma accounted for 41% of all autologous stem cell transplants in Europe in 2011.
• Acute myeloid leukaemia.
• Acute lymphoblastic leukaemia.
• Diffuse large B-cell lymphoma.

Solid malignancies

• Neuroblastoma.
• Germinal cell tumours.
• Ewing sarcoma.

Non-malignant indications

There is experience and emerging clinical-trial evidence for the use of autologous stem cell transplantation in the treatment of autoimmune conditions. These include:

• Systemic lupus erythematosus
• Systemic sclerosis
• Rheumatoid arthritis
• Juvenile idiopathic arthritis
• Multiple sclerosis
• Dermatomyositis and polymyositis
• Crohn disease.

What are the contraindications to autologous stem cell transplantation?

Contraindications for autologous stem cell transplantation can include:

• Systemic or uncontrolled infection
• Poor functional capacity
• End organ damage (cardiac, renal, hepatic, pulmonary)
• Psychological factors affecting the ability to adhere to treatment and follow-up
• Myelodysplasia on bone marrow examination.

Tell me more about autologous stem cell transplantation

Prior to the transplant, a detailed health workup is required, followed by pretransplant induction treatment which will vary depending on the condition being treated. Autologous stem cell transplantation then involves multiple steps.

• Haematopoietic stem cells are harvested by apheresis after stimulation with granulocyte colony stimulating factor (G-CSF) — apheresis is the removal of peripheral blood from which progenitor cells are removed while the rest of the blood is reinfused; G-CSF is used in more than 95% of cases due to quicker engraftment.
• Progenitor cells are less often extracted from bone marrow or umbilical cord blood.
• Sometimes G-CSF is combined with a chemotherapy drug, such as cyclophosphamide, to enhance stem cell mobilisation and reduce the tumour burden.
• Cells are cryopreserved, then infused approximately 24 hours after completion of high dose chemotherapy, often with further G-CSF to encourage engraftment.

Following the transplant, red blood cell and platelet transfusions may be required until the subsequent pancytopenia resolves. Consolidation and maintenance treatment may follow, depending on the underlying condition.

What are the benefits of autologous stem cell transplantation?

Autologous stem cell transplantation is well established for use in lymphoma and plasma cell disorders. Overall survival and progression-free survival is improved for plasma cell myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma when treated with autologous stem cell transplantation with chemotherapy compared to chemotherapy alone.

Autoimmune conditions with dermatological manifestations with the best evidence for autologous stem cell transplantation use are:

• Systemic sclerosis — 70% experience at least a 25% improvement in skin score as measured by modified Rodnan method (a measure of skin thickness)
• Systemic lupus erythematosus — remission is induced in 50–66%.

What are the disadvantages of autologous stem cell transplantation?

The main disadvantages of autologous stem cell transplantation include:

• Significant morbidity
• Variable mortality, which depends on the disease being treated, patient comorbidities, and the treatment centre
• Although transplantation prolongs survival, it does not offer a cure for plasma cell disorders
• Autologous stem cell transplantation is time-consuming and expensive.

What are the side effects and risks of autologous stem cell transplantation?

Side effects of autologous stem cell transplantation include:

• Immunosuppression, leading to bacterial, viral, and fungal infections.
• Approximately 40% of patients develop febrile neutropenia. Antiviral medication such as aciclovir and oral antifungal medications are often taken prophylactically during the high-risk period.
• Side effects of G-CSF — flu-like symptoms, myalgia/arthralgia, fever, and abnormal liver function tests.
• Side effects of chemotherapy — these vary depending on the conditioning regimen. They can include drug-induced alopecia, skin toxicity (dry skin, disorders of pigmentation, oedema, drug-induced pruritus, pustules, and drug-induced acne) and gastrointestinal disturbance (nausea/vomiting, diarrhoea, oral mucositis).
• Transplant-contaminated infection, often due to skin commensals; this is reduced by cryopreservation.
• Reactions to the red blood cell and platelet transfusions given prior to engraftment.