Allogeneic (donor) stem cell transplant for Myeloma

Overview
Stem cell transplant after high-dose chemotherapy is the most common treatment for people when first diagnosed with multiple myeloma. The purpose of a stem cell transplant in multiple myeloma is to replace cancerous bone marrow cells with stem cells that will form healthy bone marrow. Stem cell transplants usually take place after the cancerous cells of the bone marrow have been destroyed with chemotherapy, radiation, or a combination of the two.

The vast majority of people with multiple myeloma receive an autologous stem cell transplant, which means that the stem cells are harvested from their own bodies. Autologous stem cell transplants cannot cure myeloma, but the risk of severe side effects is low. Less commonly, an allogeneic transplant may be considered. In an allogeneic transplant, stem cells are harvested from a donor who may be a sibling or other close blood relative of the recipient or an unrelated person who is a good genetic match.

In some cases, an allogeneic stem cell transplant can cure myeloma. However, allogeneic stem cell transplants carry a significant risk of life-threatening side effects. Due to the risk of severe side effects, allogeneic stem cell transplant is most likely to be considered in cases involving younger people with relapsed myeloma that is considered high-risk based on genetic characteristics. Allogeneic stem cell transplant may be considered after an autologous stem cell transplant has failed.

In the past, cells for transplant were taken from bone marrow. For this reason, some people still refer to stem cell transplants as bone marrow transplants. However, blood is now the most common source for hematopoietic (blood cell producing) stem cells for transplant in cases of multiple myeloma. Stem cells sourced from the blood may be referred to as peripheral blood stem cells.

What does it involve?
Most people with multiple myeloma undergo a course of chemotherapy, radiation, or both prior to receiving a stem cell transplant.

Stem cells are usually harvested from a donor who is a close blood relative, but the donor may also be someone unrelated who is a good genetic match. Ideally, allogeneic stem cell transplants will trigger a process known as graft-versus-tumor or graft-versus-myeloma effect in which the transplanted cells help attack the cancer cells and potentially cure myeloma.

However, the greater risk of graft-versus-host disease (GVHD) often outweighs this potential benefit of allogeneic stem cell transplant. In GVHD, the transplanted donor cells attack the host’s tissues. Graft-versus-host disease ranges from mild to potentially life-threatening. Acute GVHD is very dangerous and must be treated with powerful immunosuppressant medications such as corticosteroids. Chronic GVHD may also threaten life, but in milder cases, chronic GVHD may cause limited symptoms and improve overall survival in people who receive allogeneic stem cell transplant for myeloma.

The process of receiving a stem cell transplant is similar to receiving a blood transfusion. Stem cell transplants for multiple myeloma may be administered on an outpatient or inpatient basis. Between 30 and 40 percent of people with myeloma undergo outpatient stem cell transplants, undergoing daily monitoring for side effects. The majority of people will be admitted to the hospital during the stem cell transplant process. Those admitted to the hospital for stem cell transplant can expect to stay two to three weeks during recovery.

During the first weeks of recovery from stem cell transplant, people with myeloma may receive antibiotics and antiviral or antifungal medications to help protect them against infection. They may also require transfusions of red blood cells or platelets (cell fragments involved in the clotting process) to replace those destroyed by chemotherapy. Those who have undergone stem cell transplant for multiple myeloma are often given Erythropoietin (EPO), a hormone that encourages and speeds the growth of blood cells.

After receiving a stem cell transplant, people with multiple myeloma will receive two to three years of maintenance medications to sustain the treatment response.

Intended outcomes
Stem cell transplant can extend survival in people diagnosed with multiple myeloma.

Results
Before the introduction of newer medications for multiple myeloma, the mortality rate in people who received allogeneic stem cell transplants was between 30 and 50 percent due to complications such as GVHD, fungal infections, and lung damage. The recent introduction of several new medications has improved overall results for allogeneic transplants, but the novelty of the drugs means that there is limited comparative data on long-term results such as complications and survival rate.

In one study published in 2014, 57 people with multiple myeloma received an allogeneic stem cell transplant after previously undergoing an autologous stem cell transplant. In some people, myeloma had responded to the autologous transplant; in others, the autologous transplant had had no effect. The overall five-year survival rate for all participants was 59 percent. The five-year survival rate was 82 percent in those whose myeloma had responded to the initial autologous transplant and 38 percent in those whose myeloma had failed to respond to the autologous transplant.

Constraints
Short-term side effects of stem cell transplant can include fatigue, headaches, fever and chills, nausea, vomiting, diarrhea, loss of appetite, weight loss, trouble sleeping, and skin rashes. Some people develop mucositis, inflammation of the digestive tract that can cause pain and make it difficult to eat. Some side effects, such as nausea, can be eased with other medications. Fatigue may be longer-lasting, persisting beyond the immediate recovery period. It may take months to fully recover after receiving a stem cell transplant.

For people who receive allogeneic stem cell transplants, the threat of graft-versus-host disease never fully disappears. Those who receive allogeneic stem cell transplants and show signs of GVHD may need to take immunosuppressant medications throughout their lives. Chronic GVHD can cause symptoms that affect the eyes, lungs, liver, digestive tract, genitals, and skin, hair, or nails. In severe cases, GVHD can be fatal.

In some people, myeloma fails to respond to stem cell transplant and relapses soon after the transplant.

For more details about this treatment, visit:

Stem Cell Transplant for Multiple Myeloma – American Cancer Society
https://www.cancer.org/cancer/multiple-myeloma/...

Stem Cell Transplants – Multiple Myeloma Research Foundation
https://themmrf.org/multiple-myeloma/treatment-...

Stem Cell Transplant for Multiple Myeloma – Memoral Sloan Kettering Cancer Center
https://www.mskcc.org/cancer-care/types/multipl...

Graft-Versus-Host Disease – Leukemia & Lymphoma Society
https://www.lls.org/treatment/types-of-treatmen...

What are the Side Effects of a Stem Cell Transplant? – Dana-Farber Cancer Institute
https://blog.dana-farber.org/insight/2018/02/si...

The graft-versus-myeloma effect: chronic graft-versus-host disease but not acute graft-versus-host disease prolongs survival in patients with multiple myeloma receiving allogeneic transplantation. – The Biology of Blood and Marrow Transplantation
https://www.ncbi.nlm.nih.gov/pubmed/24792872

Allogeneic hematopoietic cell transplantation in multiple myeloma – UpToDate
https://www.uptodate.com/contents/allogeneic-he...