The standard of care for fit multiple myeloma patients is to receive high-dose chemotherapy (HDT) with autologous stem cell rescue — otherwise known as autologous stem cell transplant (ASCT) — after completion of induction therapy. Autologous stem cell transplant can provide significant remission that is both long and deep, extending survival.
"Autologous" refers to the blood-making stem cells that are harvested from the patient to be a source of new blood cells after high-dose chemotherapy with melphalan. "Allogeneic" transplant, in which donor stem cells are used instead of the patient's own cells, is not performed in myeloma outside the context of a clinical trial.
Are You a Transplant Candidate?
High-dose therapy with stem cell rescue is a treatment option for many MM patients, but several factors must be taken into consideration.
Age is the first factor to consider. Transplant is usually recommended for patients under age 65. Since high-dose chemotherapy is an intensive regimen, the patient must be medically fit enough to withstand it, with no major underlying medical issues. Some older patients are in excellent physical health and can be considered fit and transplant-eligible. Transplant eligibility is evaluated on an individual basis.
These risk-related factors include the type and the stage of the disease, its aggressiveness and responsiveness to treatment, the levels of serum albumin and beta-2 microglobulin, and the presence or absence of certain chromosomal abnormalities in the patient’s myeloma cells. While there are similarities between patients, each patient’s disease has its own distinct characteristics. Therefore, general statements regarding patient outcomes both during the transplant procedure and post-transplant are inappropriate.
When to Transplant
There is no absolute clinical data to suggest that transplantation earlier in the treatment regimen is better than waiting until later. Clinical trial results suggest that frontline therapy that includes an immunomodulatory drug and a proteasome inhibitor in combination may result in response rates and duration of response comparable to those of stem cell transplant, allowing some patients to postpone transplant until later in the course of the disease. This hypothesis is undergoing continued investigation.
It’s important to remember that even if someone is a good transplant candidate, it is ultimately the patient’s decision whether or not to have a transplant. It is possible to have stem cells harvested and saved for a later treatment — if the hospital has the storage capacity and the patient's insurance company will agree to pay for harvesting for later use — leaving the patient open to other more immediate treatment options. Discuss these options with your physician and insurer.
The Transplant Procedure
Blood cell-making (hematopoietic) stem cells are located in the bone marrow. Stem cell growth factors (also known as “colony-stimulating factors”) are injected to trigger the release of bone marrow stem cells into the bloodstream. These peripheral blood stem cells are then harvested and frozen for use within days, weeks, or years in the future. There are three main methods for stimulating the growth of blood cell-producing stem cells before they are harvested:
1. giving growth factors alone
2. giving growth factors with chemotherapy
3. using a stem cell mobilization agent with growth factors.
The Harvesting and Processing of Stem Cells
The medical term for removal of hematopoietic stem cells from the circulating blood (harvesting stem cells) is apheresis, a procedure whereby blood from the patient passes through a machine that separates and then removes stem cells. The rest of the blood is immediately returned to the patient. The procedure lasts 3 to 4 hours each day for 1 to 5 days, and is usually done on an outpatient basis.
Side effects of apheresis are temporary and are caused by changes in the volume of the patient’s blood as it circulates in and out of the apheresis machine, as well as by the blood thinners added to keep the blood from clotting during the procedure. The most common side effects experienced during apheresis are slight dizziness and tingling sensations in the hands and feet. Less common side effects include chills, tremors, and muscle cramps.
After collection, the peripheral blood is taken to the processing laboratory for freezing (cryopreservation). The stem cells are mixed with a solution containing dimethyl sulfoxide (DMSO), then frozen and stored in liquid nitrogen. The stem cells can be stored frozen for as long as necessary until the time they are transplanted. Excellent function of stems cells is retained for at least 10 years.
How Many Stem Cells Do I Need?
A number of studies have been completed to determine the number of stem cells you need to safely undergo high-dose therapy. The number is quantified by a laboratory technique called “CD34+ cell analysis by flow cytometry.” A minimum number of stem cells to safely complete a transplant is 2 million CD34+ cells per kilogram of body weight. The stem cell collection process continues daily until the planned number of stem cells is collected. Most transplant physicians collect enough stem cells for two transplants (at least 4 million CD34+ cells per kilogram of body weight).
Administering High-dose Chemotherapy
After the harvested stem cells are frozen, the patient is ready to receive high-dose chemotherapy to destroy the myeloma cells. High-dose chemotherapy kills these cells inside the patient’s body more effectively than standard-dose chemotherapy.
Autologous Stem Cell Transplant or Infusion
Since high-dose treatment destroys the normal bone marrow in addition to the myeloma cells, the collected stem cells are unfrozen and given back into the bloodstream through an intravenous (into a vein) catheter one to two days after administration of the high-dose chemotherapy. This infusion is often referred to as the transplant. It is not a surgical procedure and usually takes place in the patient’s room over the course of 1 to 4 hours. Infused stem cells travel through the bloodstream to the bone marrow, where they begin to produce new blood cells, a process called “engraftment.” It takes 10 to 14 days for the newly produced blood cells to enter the bloodstream in substantial numbers, and the patient may be given growth factors to speed up this process. The average time for the chemotherapy, transplant, and recovery is approximately 3 weeks. Not all transplant centers require that patients remain in the hospital after the infusion of stem cells.
In addition to obliterating the bone marrow, high-dose chemotherapy can cause other severe side effects, which may require hospitalization for treatment during this period. Some of the more common side effects include nausea, vomiting, diarrhea, mouth sores, skin rashes, hair loss, fever or chills, and infection. Medications are given to prevent or lessen some of the expected side effects, and patients are closely monitored during and after the administration of high-dose chemotherapy.
Until engraftment of the stem cells takes place, the body’s immune system is weakened by the effects of the high-dose chemotherapy, and patients are very susceptible to developing infections. Even a minor infection like the common cold can lead to serious problems. Therefore, special precautions are necessary during recovery. Patients may remain in the hospital until the white blood cell counts reach a level safe enough for the patient to be discharged. The following supportive care measures may be required:
- Antibiotics are often prescribed to help prevent infection.
- Visitors should wash their hands and may be asked to wear masks, gowns, and rubber gloves to protect the patient.
- Fresh fruits, vegetables, and flowers may be prohibited from the patient’s room as these can carry bacteria and fungi.
- If infection or fever occurs (as the result of lowered white cell counts), the patient may be given intravenous antibiotics.
Patients and their caregivers are given instructions for maintaining a safe environment at home to help prevent infection while the immune system continues to recover.
Engraftment and Recovery
After the stem cells have been infused, many transplant centers use white blood cell growth factors (e.g., Neupogen®, Neulasta®, Leukine®) to help stimulate the bone marrow to produce normal blood cells. These injections continue until the white blood cell count returns to normal. During this time, red blood cell and/or platelet transfusions may be necessary. Once symptoms resolve and the risk of serious infections is reduced, transfusions will no longer be needed. Although patients may be well enough to leave the hospital, the recovery process will continue at home for 1 to 4 months, and patients usually cannot resume normal activities for up to 3 to 6 months, although this varies from individual to individual. Having a support network is very important during this time. Waiting for the transplanted stem cells to engraft, for blood counts to return to safe levels, and for side effects to disappear is often the most difficult time for both patients and their loved ones. It is important to take things one day at a time: one day a patient may feel much better, but the next day feel too weak to do much more than sleep.
High-dose chemotherapy with stem cell rescue can place physical, psychological, emotional, and financial stresses on patients and their families. Patients may experience feelings of anger, depression, and anxiety over an unknown future and a lack of control. We urge you to take advantage of support services offered through the hospital and other organizations, including myeloma support groups, or to seek a referral from your oncologist for psychological counseling or psychiatric consultation.