Role of Transplant

What Is Autologous Stem Cell Transplant (or Bone Marrow Transplant)?

The medical term for autologous stem cell transplant (ASCT) is “high-dose therapy (HDT) with stem cell rescue.” In myeloma, the use of HDT was introduced in the 1990s. In the 2000s, the FDA approved novel treatment options for myeloma that led to improved outcomes in ASCT-eligible patients.

More recently, the use of newer therapies throughout the disease course has significantly improved outcomes, including the efficacy of ASCT. The goal in myeloma care is to keep as many treatment options open as possible. By doing so, patients can choose therapies that offer the best chance for a deep and lasting remission. 

You can learn more about how response is assessed by reading the IMF Patient Handbook. 

Why Should a Myeloma Patient Consider an Autologous Stem Cell Transplant? 

ASCT is one of the treatment options to consider for patients with myeloma. You should discuss and compare the benefits and risks of all options available to you with the doctor treating your myeloma.  

ASCT can help patients respond better to treatment and stay in remission longer. Remission length is called progression-free survival (PFS), which is the time a patient lives with myeloma without it getting worse. While ASCT may improve PFS, overall survival (OS)—the time from diagnosis or start of treatment until death from any cause—is similar with or without transplant. As myeloma treatments get better, overall survival continues to increase.

Even if you are a good candidate for a treatment like ASCT, many factors must be considered, and the final decision is yours. That’s why seeking an opinion—or a second opinion—from an experienced myeloma specialist is important. 

Consult with a Myeloma Expert 

Myeloma is a highly individualized disease. Do NOT compare your myeloma to that of other patients. Each patient’s myeloma has its own distinct characteristics.  

Myeloma specialists at large “high-volume” treatment centers or academic institutions care for hundreds of myeloma patients, conduct clinical trials with novel myeloma therapies, and develop the expertise needed to help guide the optimal treatment strategy for your unique case of myeloma.

If an in-person consultation with a myeloma expert cannot be arranged, you or your doctor can schedule a consultation as a video or telephone call. This is a common practice, and the IMF InfoLine can help you identify one or more such specialists. Your goal is to gain a clear understanding of your options so that you can proceed with confidence. 

How to Make Your Decision About Undergoing an ASCT  

How should a myeloma patient be assessed for an ASCT?

Eligibility criteria for ASCT varies among institutions. In 2014, the IMF’s International Myeloma Working Group (IMWG) published a consensus statement. This statement said that the arbitrary age of 65 is no longer sufficient to define whether a patient is eligible or ineligible for ASCT.

Physiological age is a more important factor than chronological age.

Other considerations to evaluate appropriate treatment include:

• General fitness
• Concurrent illnesses
• Kidney function
• Heart and lungs function  
• Liver function

In the U.S., there is no upper age limit set in the Medicare National Coverage Determination for ASCT in myeloma, and the Centers for Medicare & Medicaid Services (CMS) have now removed the upper age limit on coverage. As a result, the question of eligibility is left to the patient’s doctor and the Medicare administrative contractor within the patient’s jurisdiction.

Visit cms.gov/Medicare/Coverage/DeterminationProcess for more information or speak with your healthcare team. 

Most myeloma patients can consider ASCT after finishing their initial treatment. But decisions regarding ASCT should be made based on a risk-benefit assessment. You and your doctor must consider all the relevant myeloma-related factors, including the following:

• Confirm your diagnosis of myeloma and if your disease is active and if it requires treatment.
• Discuss your response to prior treatments, as well as your current range of treatment options and their potential risks and benefits.
• Myeloma patients who have no minimal residual disease (MRD) after frontline therapy, have improved OS whether they have undergone ASCT or not.
• Your test results, such as beta-2 microglobulin (β2-microglobulin, β2M, or β2M), serum albumin, and any chromosomal abnormalities that might indicate that you have high-risk multiple myeloma (HRMM), disease that is more likely to relapse quickly after treatment.

To learn about tests used to monitor and assess myeloma, read the IMF’s publication Understanding Your Test Results.

Patient-related factors to discuss with your doctor include your personal, professional, and financial situations. 

When should a patient undergo an ASCT (timing)?

Talk to your doctor about the best timing for ASCT. Many doctors prefer doing ASCT early, during frontline therapy, because it can improve quality of life and increase the chances of long-lasting remission and MRD-negativity. If you respond well to initial treatment, stem cells can be collected and saved for ASCT later, if the disease relapses.

How is chemotherapy used as part of the ASCT process?

Chemotherapy is the use of drugs to kill cancer cells. HDT is more effective at eradicating myeloma cells from the bone marrow than standard-dose chemotherapy. But any treatment that reaches the bone marrow to kill myeloma cells is also capable of damaging normal stem cells.

If your doctor recommends ASCT, then your initial therapy should be with drugs that don’t damage your normal stem cells prior to harvesting. For example, therapy with Revlimid® (lenalidomide) for more than 4 cycles may impair stem cell collection.

How should a myeloma patient prepare for undergoing an ASCT?  

You should feel comfortable and reassured before you begin your ASCT process. You can do a lot to get ready for your ASCT. The IMF has a library of publications about the therapies used for the treatment of myeloma at every stage of the disease. All are free-of-charge and can be downloaded or requested in printed form.

Ask your doctor any questions you may have. Some transplant centers may pair you up with a fellow patient who has been through the ASCT process and can share their experience with you. If possible, bring a friend or family member to your doctor appointments. They can take notes, and ask your doctor to provide an “after-visit summary.”

Share what you learn with your loved ones. This way, they will know what to expect and how they can best help in the weeks and months ahead.

Your transplant center and team

Ask your doctor whether you will receive treatment on an inpatient or outpatient basis. Visit the transplant center and see the rooms where the ASCT process and recuperation will take place. If the transplant center location is far from your home, visit the accommodations where you will stay. Many transplant centers have accommodations nearby or can help you find suitable accommodations. 

Ask to meet your myeloma transplant team ahead of time. This includes doctors, nurses, social workers, psychologists, and other healthcare professionals. Meeting them helps you know who does what and what support is available. ASCT is complex, so your team should have experience and expertise.  

Support resources

Having a support network is very important. ASCT can place overwhelming stresses on patients and their loved ones before, during, and after the procedure. We urge you to take advantage of the support resources offered through your hospital, the IMF InfoLine and support groups, and through other patient-centric organizations. Ask your doctor about the benefits of psychological counseling or psychiatric consultation. 

Understand the Process of ASCT in Myeloma 

What are the steps in the process of autologous stem cell transplant in myeloma? 

The following are the steps in the process of ASCT in myeloma:

1. Induction therapy is given to prepare the patient for ASCT.
2. Stem cells are mobilized from the bone marrow into the bloodstream.
3. Stem cells are collected from the bloodstream, frozen, and stored in a laboratory.
4. The patient is treated with high-dose chemotherapy to kill remaining cancer cells.
5. Stem cells are thawed and infused back into the patient through a vein.
6. Stem cells travel to the bone marrow and begin producing new blood cells.

Induction therapy

Induction therapy is the initial treatment given to a patient in preparation for an ASCT. Depth of response after induction therapy is generally thought to influence the depth of response after ASCT. However, even lesser degrees of response to induction therapy may be sufficient for effective stem cell collection.  

After each treatment cycle, ask your doctor how you are responding and whether ASCT is still recommended.  

Patients have many options for induction therapy prior to ASCT. Previously, triplet (three-drug) regimens had been considered the standard-of-care (SOC) for most patients with myeloma. Recently, the FDA approved four-drug (quadruplet) regimens. Myeloma can be better controlled using multiple drugs that work in different ways (mechanisms of action). 

FDA-approved induction therapies

The triplet combinations below are listed in alphabetical order.

• Kyprolis® (carfilzomib), Revlimid® (lenalidomide), and dexamethasone [KRd]
• Velcade® (bortezomib), Revlimid, and dexamethasone [VRd]

The quadruplet combinations below are listed in alphabetical order.

• Darzalex Faspro® (daratumumab + hyaluronidase-fihj) plus KRd [DKRd] Darzalex Faspro plus VRd [DVRd]
• Sarclisa® (isatuximab-irfc) plus KRd [Isa-KRd]
• Sarclisa plus VRd [Isa-VRd] 

NCCN-listed induction therapies 

The National Comprehensive Cancer Network (NCCN) Guidelines for

Myeloma include the following induction therapies:

• Revlimid and dexamethasone [Rd],
• Velcade, cyclophosphamide, and dexamethasone [VCd or CyBorD],
• Velcade, Adriamycin® (doxorubicin), and dexamethasone [PAd],
• Ninlaro® (ixazomib), Revlimid, and dexamethasone [IRd].

The NCCN Guidelines include the following induction therapies as “useful in certain circumstances:”

• Velcade and dexamethasone [Vd],
• Velcade, thalidomide, and dexamethasone [VTd],
• Darzalex plus VTd [DVTd],
• VTd, cisplatin, doxorubicin, cyclophosphamide, and etoposide [VTd-PACE]. 

Stem cell collection before HDT

Your stem cells will be collected using a process called apheresis. A machine takes stem cells from your blood and returns the rest to you. Apheresis is usually done as an outpatient procedure for 1 to 5 days, about 3 to 4 hours each day.

One the following protocols may be used prior to harvesting your stem cells: 

1. You will be given injections with a colony-stimulating factor (CSF) to stimulate the development and growth of blood cells, and to mobilize your stem cells from the bone marrow into your bloodstream. Daily injections are followed by daily harvesting of stem cells until a sufficient quantity is collected.
2. You will receive CSF plus chemotherapy. The most commonly used drug to enhance the release of stem cells from the bone marrow into the bloodstream is cyclophosphamide. Yet, other drugs can be used instead. Ask your doctor about potential side effects.
3. You will receive CSF plus a mobilizing agent, a drug to trigger the release of stem cells into the bloodstream. This is particularly helpful for patients who have difficulty generating enough stem cells for harvesting. In 2008, the FDA approved Mozobil® (plerixafor) for stem cell mobilization in combination with a growth factor. In 2023, the FDA approved Aphexda® (motixafortide) to mobilize hematopoietic stem cells for ASCT in combination with filgrastim. 

Next, the collected stem cells are taken to a laboratory, where they are frozen in liquid nitrogen and stored at a temperature of –80°C (–112°F). Excellent function of stem cells is retained for at least 10 years.

Note: Scientific evidence indicates that “purging” myeloma cells from the harvested stem cells is not effective in ASCT for myeloma. 

High-dose therapy  

When you are ready to proceed with ASCT, your doctor will first use HDT to reduce your level of monoclonal protein (myeloma protein, M-protein) by at least 50%. HDT destroys myeloma cells in the bone marrow where they grow. It is more effective at eradicating myeloma cells from the bone marrow than standard-dose chemotherapy. However, any treatment that reaches the bone marrow to kill myeloma cells also damages your normal stem cells. The most common type of HDT used in myeloma is melphalan, administered at dose of 200 milligrams per square meter (mg/m2) of body surface area (size of patient).

Medications are given to prevent or lessen the anticipated side effects of HDT.  

What are common side effects of HDT?

• nausea
• vomiting
• diarrhea
• mouth sores
• skin rashes
• hair loss
• fever or chills 
• Infection

How Are Patients Monitored During and After ASCT?

Patients are monitored very closely during and after the administration of HDT, including daily measurement of weight, blood pressure, heart rate, and temperature. 

Stem cell rescue

Approximately 36 to 48 hours after HDT, the levels of melphalan in your body are very low and do not harm the reinfused stem cells. Your frozen stem cells are thawed and infused back into your bloodstream over a period of 1 to 4 hours. The chemical used to keep stem cells fresh has a garlic smell – you may even experience the taste of garlic. 

Engraftment

Engraftment is the process by which the reinfused stem cells migrate from the bloodstream to your bone marrow, where they begin to produce new blood cells to replace the normal stem cells destroyed by HDT. You may

Receive subcutaneous (SQ) injections of growth factors to help stimulate your bone marrow to produce normal blood cells. Your stem cells will begin to grow back within 10 to 14 days after reinfusion, and your blood counts will begin to recover. You may receive transfusions if necessary.

Some transplant centers may require you to remain in the hospital on an inpatient basis after the reinfusion, and some centers have facilities nearby where you may stay while being monitored daily at the hospital on an out patient basis. The length of stay varies patient-to-patient but is usually around 2 to 3 weeks. If you live near the transplant center, you may be able to sleep at home and come to the hospital for daily monitoring on an outpatient basis.

When you are discharged, your recovery will continue at home for about 2 to 4 months. Often, the most difficult time is waiting for the reinfused stem cells to engraft, for blood counts to return to safe levels, and for side effects to resolve. On some days you may feel better, and on other days you may feel too weak to do much more than sleep.

Frequent visits to the hospital may be required to monitor your progress. It is important to take things one day at a time. As your bone marrow produces new blood cells, symptoms resolve, the risk of serious infections is reduced, and transfusions may no longer be needed.

Depth of response

HDT with stem cell rescue delivers further improvement in the level of response achieved by induction therapy. More than half the time, partial response (PR) will be improved to either very good partial response (VGPR) or complete response (CR). The ultimate goal of HDT with stem cell rescue is to eliminate all residual myeloma cells that have not been killed during induction therapy.

The Role of Tandem ASCT

ASCT can be performed once (a “single” autologous transplant) or twice (“double” or “tandem” autologous transplants). Tandem ASCTs are usually done with an interval of 3 to 6 months between the two transplants.

Tandem transplantation for myeloma has become less common due tothe emergence of effective novel therapies.

The Role of a Second ASCT

A second ASCT is an option for patients with relapsed myeloma if they achieved response of at least an 18-month duration following their first ASCT. A second ASCT appears to be beneficial for some patients, and this is one of the reasons that enough stem cells for two ASCTs may be collected in advance of the first transplant. 

What Are the Possible Side Effects of an Autologous Stem Cell Transplant? 

Side effects are a possibility with every type of medical treatment or procedure. Each patient reacts differently at each step of the ASCT process.

No two patients share exactly the same side-effect profile. Following HDT with stem cell rescue, common potential side effects includethe following:

• nausea,
• mouth sores,
• hair loss,  
• infection,
• fatigue,  
• diarrhea, and  
• skin rash.

The appropriate management of side effects is one of the reasons why it is so important to have your ASCT at a transplant center where the doctors, nurses, and allied healthcare professionals have performed the ASCT procedure many times on many myeloma patients. Such a team is more likely to have the expertise to care for each individual patient’s needs.

Until engraftment of the infused stem cells takes place, patients are very susceptible to developing infections. Certain infections can cause serious complications or be potentially life-threatening. Even a minor infection like the common cold can lead to complications because the body’s immune system is weakened by the effects of HDT. To protect the patient and prevent infection, the following supportive care measures may be required:

• Antibiotics to help prevent infection.
• Visitors may be asked to wash their hands, and wear masks and rubber gloves.
• Fresh fruits, vegetables, and flowers may be prohibited from the patient’sroom as these can carry infectious agents such as bacteria and fungi.

If infection or fever occurs, the patient may be given an intravenous (IV) infusion of antibiotics into the vein. 

How to Resume Your Life After Undergoing an ASCT

Data from the Health Resources and Services Administration (HRSA) demonstrate that 99.1% of myeloma patients in the U.S. are alive at 100 days following ASCT.

After your ASCT, you will need to rely upon your medical team as well as on the support of a care partner. It is not uncommon for patients to experience a loss of the sense of independence, while at the same time experiencing feelings of isolation, depression, and helplessness. Patients and their care partners may consider seeking assistance from a trained counseling professional. There may also be benefits to participating in patient support groups either in-person or virtually.

On average, it takes 3 to 6 months to recover from an ASCT. By this time, your bone marrow will be producing healthy blood cells and your immune system will once again be able to fight infection. Your hair will grow back.

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