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TRANSPLANT
07.01.15

In the context of myeloma treatment, transplant refers to the infusion or administration of blood stem cells. It is therefore called a stem cell transplant or “SCT.” The procedure is currently very safe when a patient’s own stem cells are used as the replacement cells, which is why the procedure is called autologous stem cell transplant or ASCT. 

Are You a Transplant Candidate?

  • A stem cell transplant is a treatment option for many myeloma patients. However, it is not a cure. It can improve the duration of remission and survival. It can also provide a better quality of life for most patients. Not all patients with myeloma are candidates for a stem cell transplant. Many factors must be taken into consideration. These include factors related to the myeloma itself and patient-related factors.

PATIENT-RELATED FACTORS

Age is the first factor to consider. Transplant is routinely considered for patients under age 65 years. Since stem cell transplant is a rather onerous procedure, the first requirement is to be generally medically fit to undergo such a procedure. There must be no major underlying medical issues related to heart, lung, kidney, or liver disease. Also, such issues as active infection or poorly controlled sugar diabetes or high blood pressure for example can be a serious concern.

Eligibility for stem cell transplant must be evaluated on an individual basis. Many older patients are in excellent physical health and would be considered fit and transplant eligible.

DISEASE-RELATED FACTORS

These include the type of myeloma; the stage of the disease; its aggressiveness and responsiveness to treatment; serum albumin; beta-2 microglobulin; and chromosome analysis.

It is important to note that myeloma is a highly individualized disease. While there are similarities between patients, each patient’s disease has its own distinct characteristics. Testing will determine how much myeloma there is in your body and how aggressive it is and this information, combined with the aforementioned factors, will help  determine whether a transplant is appropriate for you. Therefore, general statements regarding patient outcomes both during the transplant procedure and post transplant are inappropriate.

Purpose of a Transplant

Transplant or infusion of blood stem cells is used to rescue the bone marrow after the administration of very high dose chemotherapy such as with melphalan. The treatment is the high dose melphalan. The stem cell transplant is to repopulate or re-grow blood stem cells in the bone marrow since they have also been wiped out by the high dose melphalan.

When to Transplant

Most transplant physicians believe it is better to perform the transplant early in the disease course. [Does this need updating? Are doctors now waiting longer before ASCT?] However, there is no absolute clinical data to suggest that transplantation earlier in the treatment regimen is better than waiting until later. Recent trial results suggest that frontline therapy that includes the anti-myeloma agents thalidomide, Revlimid®, and/or VELCADE® 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 is undergoing further investigation. 

Remember, in most cases, unlike a heart attack, myeloma gives the patient the luxury of time to do some homework and to gather the information needed to make an informed decision about what’s right for him or her. For example, one could have stem cells harvested and saved for a later treatment. This leaves the patient open to other more immediate treatment options. These are things to discuss with the doctor. It’s important to remember that even if someone is a good transplant candidate, the ultimate decision about whether or not to have a transplant is the patient’s.

The Transplant Procedure

Blood stem cells are located in the bone marrow.  Stem cell growth factors or colony-stimulating factors such as Neupogen®, Neulasta®, or Leukine® are injected to trigger the release of bone marrow stem cells into the bloodstream. These peripheral blood stem cells are then harvested for use within the next few days, weeks or even years in the future.

There are three main methods for collecting stem cells:

  • giving growth factors alone
  • giving growth factors with chemotherapy
  • using a mobilization agent with growth factors.

The Collecting or Harvesting Procedure

In medical language, the harvesting is called apheresis or leukapharesis – literally the removal of white cells from the blood stream. Apheresis is a procedure whereby blood from the patient or donor passes through a special machine that separates (using a centrifuge technique) and then removes stem cells. The rest of the blood is immediately returned to the patient or donor. Compared to direct bone marrow harvesting, this is a remarkably simple and pain-free procedure.

Apheresis/Leukapheresis: Prior to the start of apheresis, a thin flexible plastic tube called a catheter is inserted through the skin and into a vein so that the blood can be taken out. The catheter is usually inserted into the chest just below the collarbone. Insertion of the catheter is usually done as an outpatient procedure, and only a local anesthetic is necessary. The site where the catheter enters the skin may be sore for a few days; the discomfort may be relieved with medications like acetaminophen (Tylenol®). The catheter may be kept in place for several weeks because it can be used to give chemotherapy after stem cells have been collected. Sometimes the same catheter is used during the transplant procedure as well. The apheresis procedure will last 3 to 4 hours each day for 1 to 5 days. Aphresis is usually done as an outpatient 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. These side effects 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 apheresis.

Processing stem cells: After collection, the peripheral blood (or occasionally direct bone marrow material) is taken to the processing laboratory, which is usually located within the hospital or local blood bank. I the processing laboratory, the bone marrow or blood cells are prepared for freezing (cryopreservation). The stem cells are mixed with a solution containing the chemical DMSO (dimethyl sulfoxide) to prepare the stem cells for freezing. The stem cells are then frozen and stored in liquid nitrogen. The stem cells will be frozen until the time they will be needed for the transplant. They can be stored frozen for as long as necessary. There is some deterioration with time, but excellent function of stems cells is retained for at least ten years.

How many stem cells do I need? 

Over the years, a number of studies have been completed to determine the number of stem cells you need to safely undergo high-dose therapy. The number of stem cells is quantified by a special laboratory technique called “CD34+ cell analysis by flow cytometry.” A small sample of the stem cell collection is tested for the number of CD34+ cells in the product. We know that a minimum number of stem cells to safely complete a transplant is 2 million CD34+ cells per kilogram of body weight. The number of CD34+ cells is checked in each daily collection and the number tallied. The stem cell collection process continues daily until the planned number of stem cells is collected – usually 1 to 4 days. Some transplant centers check the number of CD34+ cells BEFORE starting leukapheresis to make certain there will be a good collection that day. Most transplant physicians collect enough stem cells for two transplants (over 4 million CD34+ cells per kilogram body weight).

Administering High-Dose Chemotherapy
After the stem cells are frozen and stored, the patient is ready to receive high-dose chemotherapy. This treatment is designed to destroy myeloma cells more effectively than standard-dose chemotherapy. The purpose of high-dose chemotherapy is to kill myeloma cells inside the patient’s body. The most common type of high-dose chemotherapy used to treat myeloma is melphalan administered at a dose of 200 milligrams per square meter (mg/m2) of body surface area (size of patient). Depending on the type of myeloma and other factors, some patients may receive a second transplant 3 to 6 months after the first transplant (double or tandem transplant). A patient should discuss with the doctor the pros and cons of more than one transplant planned and performed back-to-back versus the possibility that the cells will be stored for a potential second transplant at a later time.

Autologous Stem Cell Transplant or Infusion
Since high-dose treatment destroys the normal bone marrow in addition to the myeloma cells, the blood stem cells must be given back to restore the bone marrow. The previously collected stem cells will be unfrozen and given back, through a catheter, into the bloodstream (as one would receive a blood transfusion) one to two days after administration of the high-dose chemotherapy. This procedure is often referred to as the transplant. The transplant takes place in the patient’s room: it is not a surgical procedure. The frozen bags of bone marrow or blood cells are thawed in a warm water bath, and then injected into the bloodstream through the catheter. Upon thawing, the DMSO (freezing agent) evaporates into the air and creates a distinct and somewhat unpleasant garlic smell. Most centers infuse one bag at a time. It usually takes 1 to 4 hours for the infusion. Infused stem cells travel through the bloodstream, and eventually, to the bone marrow, where they begin to produce new white blood cells, red blood cells, and platelets. It takes 10 to 14 days for the newly produced blood cells to enter the bloodstream in substantial numbers. Growth factors may again be given to the patient to speed up this process. In addition to obliterating the bone marrow, high-dose chemotherapy can cause other severe side effects, which may require that some patients be admitted to the hospital for treatment during this period. (Not all transplant centers require that patients remain in the hospital after the infusion of stem cells; some have facilities close by where patients may stay and be monitored daily at the hospital on an out-patient basis, while others allow patients who live close to the hospital to sleep at home and be monitored at the hospital). The average time in the hospital (or a nearby facility) for the chemotherapy, transplant, and recovery is approximately 3 weeks. Shortly before starting chemotherapy, patients usually are given large amounts of fluid to prevent dehydration and kidney damage from the chemotherapy. Some of the more common side effects of chemotherapy include nausea, vomiting, diarrhea, mouth sores, skin rashes, hair loss, fever or chills, and infection. Medications designed to prevent or lessen some of the expected side effects of treatment are given routinely. Patients are very closely monitored during and after the administration of high-dose chemotherapy. Monitoring includes daily weight measurement as well as frequent measurements of blood pressure, heart rate, and temperature.

Preventing Infection
During the first 2 to 3 weeks after transplantation, the re-infused stem cells migrate to the bone marrow and begin the process of producing replacement blood cells, a process called engraftment. Until engraftment of the stem cells takes place, patients are very susceptible to developing infections. Even a minor infection like the common cold can lead to serious problems because the body’s immune system is so weakened by the effects of the high-dose chemotherapy. Therefore, special precautions are necessary during recovery. Since the patient’s immune system is very weak, patients may remain in the hospital until the white blood cell counts reach a level safe enough for the patient to be discharged.

To prevent infection, 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 and rubber gloves to protect the patient.
• Fresh fruits, vegetables, and flowers may be prohibited from the patient’s room as these can carry infection (bacteria and fungi).
• If infection and/or fever occurs (as the result of lowered white cell counts), the patient may be admitted to the hospital and be given intravenous antibiotics.

Engraftment and Recovery
Once the stem cells have been re-infused, it will take about two weeks for blood counts to recover. Many transplant centers will again use white blood cell growth factors (Neupogen, Neulasta, Leukine) after the transplant to help stimulate the bone marrow to produce normal blood cells. These injections (under the skin) will continue until the white blood count returns to normal. During this time, red blood cell and/or platelet transfusions may be necessary.

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 family and friends. During this period patients will feel weak and very fatigued. Having a support network is very important during this period. Recovery can be like a roller coaster ride: one day a patient may feel much better, only to awake the next day feeling as sick as ever. It is important during this period to take things one day at a time. Once new blood cells are being made, symptoms will resolve, the risk of serious infections will be reduced, and transfusions will no longer be needed.

After being discharged from the hospital, a patient continues recovery at home for two to four months. Although patients may be well enough to leave the hospital, their recovery will be far from over. For the first several weeks the patient may be too weak to do much more than sleep, sit up, and walk a little around the house. Frequent visits to the hospital will be required to monitor progress. Patients usually cannot resume normal activities or return to fulltime work for up to three to six months after the transplant, although this varies from individual to individual.

Psychosocial Issues

High-dose chemotherapy and autologous transplantation can place an enormous stress on patients and families. Physical, psychological, emotional, and financial stresses can be overwhelming. Patients and families may experience feelings of anger, depression, and anxiety over an unknown future and a lack of control.

Support services offered through the hospital and many other organizations, including myeloma support groups, are very important during this time. We urge you to take advantage of these services, or to seek a referral from your oncologist for psychological counseling and/or a psychiatric consultation.    

 

REFERENCES

©2015 International Myeloma Foundation

 related articles
IMWG Consensus Statement Regarding the Current Status of Allogeneic Stem Cell Transplantation for Multiple Myeloma
International Myeloma Workshop 2011
NEWLY DIAGNOSED MYELOMA <65 YEARS: FACTS & QUESTIONS
Dr. Cavo - How I treat a patient eligible for high dose therapy and auto-transplant?
STEM CELL TRANSPLANT: The Current Status of Allogeneic Stem-Cell Transplantation for Multiple Myeloma
Long-Term Follow-Up of Autotransplantation Trials for Multiple Myeloma: Update of Protocols Conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences
STEM CELL TRANSPLANT: The current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)
STEM CELL TRANSPLANT: Mobilization in myeloma revisited: Perspectives on stem cell collection following initial therapy with thalidomide, lenalidomide or bortezomib-containing regimens


You might also be interested in:

IMWG Consensus Statement Regarding the Current Status of Allogeneic Stem Cell Transplantation for Multiple Myeloma

International Myeloma Workshop 2011
NEWLY DIAGNOSED MYELOMA <65 YEARS: FACTS & QUESTIONS
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Michele Cavo, MD
Università di Bologna
Bologna, Italy
May 3-6, 2011
Paris, France

STEM CELL TRANSPLANT: The Current Status of Allogeneic Stem-Cell Transplantation for Multiple Myeloma
Review Article
Published in the Journal of Clinical Oncology, Volume 28, Number 29, October 10, 2010

Long-Term Follow-Up of Autotransplantation Trials for Multiple Myeloma: Update of Protocols Conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences
Journal of Clinical Oncology, 2010

STEM CELL TRANSPLANT: The current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)
Published in Leukemia (2009), 1–9

STEM CELL TRANSPLANT: Mobilization in myeloma revisited: Perspectives on stem cell collection following initial therapy with thalidomide, lenalidomide or bortezomib-containing regimens
Blood First Edition Paper, prepublished online June 26, 2009