Autologous hematopoietic stem cell transplant (AHSCT) is the process of transplanting hematopoietic stem cells (HSCs) — cells in the bone marrow from which all kinds of blood cells, such as red blood cells, white blood cells, and platelets originate — into patients, so their body can create new and healthy blood cells to compensate for their loss in diseases such as multiple myeloma.

The term ‘autologous’ indicates that these cells are harvested (taken) from a patient instead of from a donor.

How AHSCT works?

In multiple myeloma, plasma cells — a type of white blood cell — start growing out of control and interfere with the proper functioning and development of HSCs in the bone marrow, which are required for blood-cell production.

After chemotherapy, AHSCT resets the existing erroneous HSCs in the bone marrow and populates them with fresh ones to restart the development of blood cells and proper immunity.

How is AHSCT performed?

AHSCT is done in a multi-step process, which can vary depending on the patient, the disease, and the transplant center. However, common procedures include the following:

Evaluation and planning

Before performing AHSCT, the patient is evaluated carefully for compatibility with the transplant. The hospital’s transplant team informs the patient about the procedure and how to prepare for it, including details of how long they will need to stay in the hospital. During this time, the patient and their family members may want to plan for expenses  they could incur.

As part of the pre-transplantation procedure, most patients will be given a central line — a thin, flexible plastic tube with multiple ports that is inserted into a major vein in the chest. The central line allows the infusion and withdrawal of blood and medications without having to use multiple needles.

HSC harvesting

HSC collection (harvesting) can be done either from the bone marrow or from the blood. Harvesting HSCs from blood is usually preferred, as it does not require anesthesia or hospitalization.

Before harvesting HSCs from the blood, the patient is treated with a growth factor — such as granulocyte colony-stimulating factor (GCSF) — to mobilize sufficient quantities of HSCs into the bloodstream. The blood is then passed through an apheresis device to separate HSCs from the blood. The HSCs are collected and frozen while the rest of the blood is returned to the person.

Myeloma patients may also be given induction chemotherapy with a combination of Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone (RVD) before HSCs are harvested in order to reduce tumor burden.

Myeloablative therapy

Myeloablative therapy, also called a conditioning regimen, is the process of reducing bone marrow activity by using high doses of chemo and/or radiotherapy. This process also destroys HSCs in the bone marrow.

The standard conditioning regimen for multiple myeloma patients is 200 mg per square meter of Alkeran (melphalan). During this process, which usually lasts between five and 10 days, the patient is highly prone to infections. For this reason, antibiotics, antivirals, and/or antifungal medications are given for protection.

HSC reinfusion

The harvested, frozen HSCs are now thawed and reinfused or transplanted back to the patient via the central line. Each infusion may take between 30 minutes to one hour, and multiple infusions may be required. The infused HSCs travel to the bone marrow and start producing normal blood cells. This is called engraftment. Successful engraftment is measured by an absolute neutrophil count (ANC) and platelet count test.

ANC should be 500 or more for three days in a row when counted 10 to 20 days after the transplant. At this time, platelet count should be between 20,000 and 50,000.

Many transplant centers use white blood cell growth factors, such as Neupogen (filgrastim), Neulasta (pegfilgrastim), or Leukine (sargramostim), to promote the production of white blood cells following the transplant.

The recovery process usually takes between one to four months, and it may be up to six months before patients are able to resume their normal activities.

AHSCT in clinical trials

The efficacy of AHSCT has been demonstrated in many clinical trials involving chemo and/or radiotherapy.

A Phase 2 clinical trial (NCT01008462) to assess the benefits of AHSCT followed by a donor-matched bone marrow transplant in treating cancers such as multiple myeloma finished in June 2018. The study evaluated the feasibility of studying different biomarkers involved while using various chemotherapy agents such as Vepesid (etoposide), Alkeran, cyclophosphamide, and Fludara (fludarabine).

The efficacy of using the RVD combination as induction chemotherapy was evaluated in a Phase 3 clinical trial (NCT01191060) with and without AHSCT. The results indicated that RVD in combination with AHSCT led to longer progression-free survival times although it did not significantly change overall survival.

The efficacy of using Ninlaro (ixazomib) as maintenance therapy following AHSCT is being evaluated in a Phase 3 clinical trial (NCT02181413) involving 658 patients with multiple myeloma. The study is expected to finish in June 2025. Preliminary results showed that Ninlaro reduced disease progression and is a viable post-AHSCT maintenance therapy.

Other information

Some patients may undergo a second AHSCT called a tandem transplant, the rationale being that a second dose of conditioning Alkeran therapy can improve the hematological response. Tandem transplant is usually performed within six months of the first AHSCT.

Low-dose maintenance therapy with Revlimid is usually carried out for deeper hematological response and improved progression-free survival.

Despite a successful AHSCT, myeloma can still relapse. In patients whose first AHSCT was deemed successful, a second round of AHSCT called salvage therapy may be considered after 36 months of AHSCT with maintenance therapy.

Common side effects of AHSCT include mouth sores, nausea, hair loss, and a slight risk of developing secondary cancers. Some patients may experience what is called engraftment syndrome, which is a combination of fever, skin rash, nausea, diarrhea, and pulmonary edema (fluid in the lungs).

AHSCT may also trigger an autoimmune reaction called an autologous graft versus host disease (GVHD), which can be life-threatening.

 

Last updated: Nov. 14, 2019

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Myeloma Research News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health providers with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website

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Özge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.