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Stem Cell Transplant

STEM CELL TRANSPLANT

STEM CELL TRANSPLANT

Stem cells are cells that can be used to “repopulate” the bone marrow.  They are normally found in the bone marrow and in the blood.  There are several types of stem cell transplantation approaches that may be used to treat myeloma. Many myeloma centres have a general rule that stem cell transplant is not routinely offered to people above a certain age, such as 70 or 75 years.  These are not hard-and-fast rules.  The important thing is not your chronological age but rather your biological age – how generally healthy you are.  An otherwise healthy 72-year-old may be a good candidate for ASCT, whereas a 66-year-old with multiple health problems may be a poor candidate.

Autologous stem cell transplantation (ASCT) is the most common.  It is referred to as an “autograft” because it uses your own stem cells. Stem cells can be obtained from blood in the veins (a peripheral blood stem cell or PBSCT), your bone marrow, or even from the blood of an umbilical cord (something few adults currently have access to).  A transplant consists of the following steps:

  1. If the stem cells are being harvested from the peripheral blood, drugs are used to “mobilize” them.  By using a medication called a Granulocyte-Colony Stimulating Factor (G-CSF) (e.g. Neupogen®) with or without chemotherapy, the bone marrow is stimulated to increase the number of stem cells in the blood.  A process called pheresis is then used to collect the stem cells from the blood.  
  2. The stem cells that are collected are frozen and stored until it is time for transplant.
  3. Before transplant, the patient undergoes a “conditioning regimen” of high dose chemotherapy with a drug such as melphalan to destroy the cancer cells in the bone marrow.  In the process, it will also destroy the blood-producing cells in the bone marrow.
  4. Within a few days of completing the high-dose chemotherapy, the stored stem cells are thawed and infused back into the patient.  In time, the transplanted stem cells begin to produce new blood cells

All treatments have both their risks and benefits.  However, studies have shown that on average, people who undergo ASCT live longer than those who receive chemotherapy alone.

Allogeneic transplant involves collecting stem cells from someone else, usually a blood relative. The donor’s cells must match the recipient’s tissue type – note that this is different from blood type and if considered requires special blood testing.  The transplanted donor stem cells may also help attack any myeloma cells remaining in the patient’s bone marrow.  This is referred to as the graft-versus-myeloma effect.

Few patients are good candidates for allogeneic transplant.  It is difficult to find good donor matches and the procedure has a greater risk of complications, including infections, graft-versus-host disease (GVHD, a potentially life-threatening condition in which the donor’s bone marrow attacks and destroys the patient’s own tissue), and death.  For these reasons, allogeneic transplant is not a standard therapy for myeloma.  

There are two types of allogeneic transplant:

  1. Ablative or “full” – high-dose therapy is used to condition the bone marrow before transplant, which destroys the patient’s own bone marrow cells
  2. “Mini” or non-myeloablative – before transplant, a moderately high-dose chemotherapy conditioning regimen is used that does not destroy the patient’s bone marrow cells but rather causes enough immunosupression to allow the donor cells to grow in the patient’s bone marrow

syngeneic stem cell transplant refers to a transplant using stem cells taken from an identical twin.  The prognosis for syngeneic transplants is better than that of allogeneic transplants; however, this is an option for only a small number of patients.  A matched unrelated donor (MUD) transplant refers to a transplant using stem cells taken from a donor who is not a relative but has the same tissue type.

Tandem (double) autologous transplants are performed in some centres.  For a tandem transplant, the plan is to conduct a second transplant within six months of the first one.  This approach may be beneficial for people who do not have a full response to the first transplant or who have “high risk” disease, as indicated by age or genetics (cytogenetics).  

An experimental approach is ASCT followed by a mini-allogeneic transplant.  In this version, a patient first undergoes high-dose chemotherapy to reduce the overall number of myeloma cells, followed by an autologous transplant.  Next there is a second course of moderately high-dose therapy with an allogeneic transplant of donor stem cells.  The second course of therapy – in combination with the help of the allogeneic transplant –should reduce the number of myeloma cells.

10 STEPS TO BETTER CARE™: Transplant - Do You Need One?
IMWG Consensus Statement: Allogeneic Stem Cell Transplantation

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?
Michele Cavo, MD
Università di Bologna
Bologna, Italy
May 3-6, 2011
Paris, France
Is There a Place for Allogeneic Transplantation in Myeloma in the Era of Novel Agents?
Rebuttal by Drs. Mehta and Fermand followed by Q & A Period

Is there a role for Allo Tx? - Favor
XIIth International Myeloma Workshop in Washington, DC
Jayesha Mehta, M.D.
Northwestern Medical School
Chicago, Illinois
Is there a role for Allo Tx? - Against
XIIth International Myeloma Workshop in Washington, DC
Jean Paul Fermand, M.D.
Hôpital Saint-Louis
Paris, France

Mozobil
Mozobil (plerixafor injection) is approved by the United States Food and Drug Administration (FDA) to be used with another agent granulocyte-colony stimulating factor (G-CSF), to mobilize stem cells into the peripheral blood for collection and subsequent autologous transplantation in patients with myeloma.