Stem Cell Transplant Treatment Side Effects

Since they were first introduced more than 60 years ago, stem cell transplants have cured or extended the lives of millions diagnosed with aggressive lymphomas, leukemias, myelomas and other blood cancers.

One type of transplant, called an allogeneic transplant, uses stem cells from a donor. But in many cases, a transplant may use stem cells from a patient’s own body. This is called an autologous stem cell transplant.

We talked with Partow Kebriaei, M.D., to learn more about what happens when a patient becomes their own donor.

What are hematopoietic stem cells?

The immature, undeveloped cells that live in the bone marrow where blood is made are called hematopoietic stem cells. Hematopoietic means blood-forming. These “baby” cells have not yet decided which type of blood cell they want to be when they grow up. Eventually, they’ll mature into one of three types:

• white blood cells to fight infection
• red blood cells to carry oxygen throughout the body
• platelets to control bleeding

Who needs a stem cell transplant, and why?

Patients with blood cancers receive high doses of chemotherapy to wipe out cancer cells in the bone marrow. The powerful treatment kills not only cancer cells, but also healthy, blood-forming stem cells. These hematopoietic stem cells need replacing after the chemotherapy ends so the body can continue making blood.

What is an autologous stem cell transplant?

Some patients rely on healthy donors for stem cells. Others “bank” their own stem cells, which will be transplanted back into their bone marrow after the high-dose chemotherapy treatment is complete. This type of transplant is called autologous. Auto means self.

Who is eligible for an autologous stem cell transplant?

Autologous stem cell transplants are an option for patients whose cancer is in remission or has stabilized. This type of transplant is used most frequently to treat multiple myeloma and lymphoma.

Leukemia patients usually receive an allogeneic stem cell transplant.  That’s because research has shown that stem cells from donors help prevent leukemia from returning.

What are the steps in an autologous stem cell transplant?

1. Collecting the stem cells: Before treatment begins, a needle is inserted into the patient’s arm vein. Blood is withdrawn and redirected into a special machine that removes about 4 million stem cells – the amount needed for a transplant. The stem cells are frozen until needed, and the rest of the blood is returned to the patient’s body. 
   
   
2. Conditioning: The patient receives high doses of chemotherapy to kill cancer cells and prepare, or “condition,” the body for transplant. This typically takes one to seven days.
   
   
3. Transplanting the stem cells: After conditioning is completed, the stem cells are thawed and reintroduced into the recipient’s vein through an IV. The stem cells automatically migrate to the bone marrow. About two weeks later, they begin producing normal, cancer-free blood cells.

What happens after an autologous stem cell transplant?

Many transplant recipients agree that the several weeks following transplant are the most challenging. Their blood counts are still very low during this time. Infection risk is high due to lack of infection-fighting white blood cells. Patients may be anemic due to lack of red blood cells. They’re also at risk for bleeding due to lack of platelets.

Doctors prescribe antibiotics to prevent infections, and patients will likely need transfusions of platelets and red blood cells. During this time, they’ll still be experiencing side effects of the chemotherapy they received during conditioning. Side effects may include nausea, diarrhea, hair loss, mouth sores and fatigue.

Most autologous transplant patients see a steady return to normal blood counts within two to four weeks. They can usually return to their normal activities in three to six months.

What’s the difference between a stem cell transplant and a bone marrow transplant?

In the early days, stem cells were collected directly from the bone marrow. Patients were taken to the operating room, anesthetized, and doctors inserted needles to remove bone marrow from the hip bone. Stem cells were extracted from the marrow and frozen until transplant day. This is where the term “bone marrow transplant” originated.

Today, we use medications that stimulate the stem cells to move out of the bone marrow and into the bloodstream, where they can be collected more easily. Stem cell transplant is very similar to bone marrow transplant, except the stem cells are harvested from the patient’s bloodstream rather than from the bone marrow.

What’s the main advantage of an autologous stem cell transplant?

A successful autologous stem cell transplant helps many people with lymphoma or multiple myeloma become cancer-free or delays the cancer’s return. Patients who use their own cells avoid graft vs. host disease, which occurs when the body views cells from a donor as foreign and attacks them.

Is one autologous stem cell transplant enough?

Most patients need only a single autologous transplant. Others, particularly those with multiple myeloma, may receive a planned second transplant several months after the first one. This is called a tandem transplant.

What’s your advice for patients considering an autologous stem cell transplant?

Recovery is a slow process, so patience is required. Most patients go from feeling lousy the first month after transplant to feeling back to normal six months later.

But everybody’s different. Some patients recover in three months, and some need a year to regain their strength and stamina. Take one day at a time, and you’ll get through it. Your MD Anderson team is here to support you every step of the way.

Request an appointment at MD Anderson online or by calling 1-877-632-6789.

When chemotherapy alone isn’t successful in treating blood cancers like leukemia and lymphoma in pediatric patients, a stem cell transplant may be an option. They can also help treat some non-cancerous bone marrow diseases, like sickle cell disease, thalassemia, severe aplastic anemia and Kostmann syndrome.

To learn about pediatric stem cell transplants and what parents should know, we spoke with Priti Tewari, M.D.

What is a stem cell transplant?

Stem cells are produced in our bone marrow; they mature to become our red blood cells, white blood cells, platelets and the cells of our immune system.

Stem cell transplants replace damaged or defective stem cells with healthy cells. They can also help replace a weakened immune system. There are two types:

• Autologous stem cell transplants use a patient’s own stem cells to help fight cancers like high-risk Hodgkin lymphoma, Ewing’s sarcoma, medulloblastoma and neuroblastoma. These cancers may require high doses of chemotherapy. Autologous transplants use patients’ own healthy stem cells to help with recovery.
• Allogeneic transplants replace patients’ stem cells with healthy cells from a donor.

Are stem cells transplants safe for kids?

Stem cell transplants come with risks, but they can be an option for patients as young as only a couple months old.

With some non-cancerous diseases like severe combined immunodeficiency, the transplant should take place as soon as possible. Pediatric patients with this condition often have weaker immune systems and are at greater risk for infection.

With some inherited disorders, we may watch your child for a few years and allow the organs to mature a little bit before moving ahead with a stem cell transplant.

What are allogeneic stem cell donor options for pediatric patients?

Suitable donated stem cells should match your child’s cells. Siblings are sometimes -- but not always -- a match. If a sibling isn’t an option, we can look for a matched unrelated donor through the National Marrow Donor Program.

If we can’t find a matched donor, we can use an alternate donor. That could be a mismatched unrelated donor, an umbilical cord blood donation or a haploidentical donation, which is a half-matched family member like a parent or sometimes a sibling.

If you have a child with a condition that may require a stem cell transplant and you’re expecting a baby, it could be beneficial to preserve the baby’s umbilical cord in a process called umbilical cord blood banking. If the siblings’ cells are a match, the banked cord may be used for a transplant later.

How are donated stem cells extracted?

They’re extracted in two ways. With peripheral withdrawal, the donor receives growth factor shots to stimulate stem cell production. The cells are then removed intravenously by apheresis, a process like blood donation.

The second approach is called bone marrow harvesting. It removes the stem cells from the pelvic bone through a surgery; it requires general anesthesia. 

We decide which approach is best based on the diagnosis, the donor’s physical size and the child’s overall health. If the donor is another child, we take special precautions. We want to ensure the donor is willingly entering this process. At MD Anderson, the donating child meets with a separate doctor on our team, a psychologist, our ethicist and a child life specialist to ensure they understand the procedure.

How do patients prepare for a stem cell transplant?

To wipe out cancer cells and to help make space for the new stem cells, patients receive chemotherapy before the transplant. Some high-risk acute lymphoblastic leukemia patients may also receive total body irradiation, a type of radiation therapy.

If your child is receiving an allogeneic transplant, we often use immunosuppressive agents to help lower the risk of a side effect called graft-versus-host disease, which is when the patient’s body rejects the donated cells.

What are the side effects of a pediatric stem cell transplant?

Many patients experience pancytopenia, which is a decrease in red blood cells, white blood cells and platelet counts.

The conditioning chemotherapy and radiation therapy commonly cause mucositis, which is irritation and ulcers throughout the digestive tract and mouth. Patients also can have painful sores, stomach discomfort and diarrhea, but medications can help.

Also, it’s rare, but the organs that help process chemotherapy -- such as the kidneys, liver and lungs -- are at risk for failure.

Another risk is infection. During and following a stem cell transplant, patients have no immune system to help fight infections. So, even a cold can be dangerous.

But we closely monitor patients to identify side effects before they become life-threatening. That’s one of the reasons why patients stay in the hospital for about four to six weeks, but sometimes it’s more. Our goal before your child leaves the hospital is for the new stem cells to start growing inside the body. We also want to get your child comfortable and walking, taking sips of water and sleeping comfortably until their blood counts are up again. Once they’re well enough to leave the hospital, they’ll start coming in for checkups three to five days a week.

Do stem cell transplants affect fertility?

Cancer and its treatment can affect fertility. Every patient who’s beyond puberty sees our fertility specialists to learn about their risks and options.

It’s also very important to discuss fertility with patients with non-cancerous diseases since these conditions are often hereditary. We want to make sure patients understand what that means for their future children and what options they have for starting a family.

What does life look like after a stem cell transplant?

If all goes well, life typically starts feeling normal about a year after the transplant.

During that year, we’re weaning down the immunosuppressive agents to help build up your child’s immune system. So, if they go back to a traditional school and they get a virus from somebody, their bodies can fight it.

If your child has siblings in school, they’ll be exposed to germs. It can be challenging, but it’s important for everyone to wash their hands and avoid sharing cups, utensils and food. It’s very important to avoid being around others with colds or the flu, too.

What research is underway in kids with blood diseases?

CAR T cell therapy is a new type of immunotherapy that’s given like a stem cell transplant. It’s being used to treat B-cell acute lymphoblastic leukemia and certain lymphomas in patients ages 25 and younger. But the side effects can be severe. MD Anderson has developed the first guidelines for managing these side effects in kids to help more patients receive CAR T cell therapy more safely.

What's your advice for families considering a stem cell transplant?

There's a lot to learn, and it can be overwhelming. Ask your care team for resources to learn more at your own pace.

Request an appointment at MD Anderson online or by calling 1-877-632-6789.

Between 20% and 70% of patients who receive an allogeneic stem cell transplant as a part of their cancer treatment will develop at least a mild case of a condition called graft vs. host disease, or GVHD.

But what is graft vs. host disease, exactly, and why does it happen? How can it be prevented and treated?

We spoke with stem cell transplant specialist Amin Alousi, M.D., director of MD Anderson’s GVHD program. Here’s what he had to say.

What is graft vs. host disease?

Graft vs. host disease is a treatment side effect that sometimes develops in patients with leukemia, lymphoma, or other blood- or lymph-based cancers who’ve had an allogeneic stem cell transplant.

These patients receive healthy, blood-forming stem cells from a donor after being given chemotherapy and/or radiation therapy to destroy their own immune system and treat their cancer. The donor’s cells then engraft themselves in the patient’s bone marrow and start rebuilding their new host’s immune system by generating new white blood cells, red blood cells and platelets.

GVHD occurs when the donor’s immune cells recognize proteins expressed by a patient’s tissues and organs as foreign and attack them as if they were invaders.

What are the symptoms of graft vs. host disease?

It really varies depending on the type of GVHD and individual.

Acute GVHD typically occurs within the first few months after a stem cell transplant and has a distinct presentation that can include:

• skin rash
• nausea
• vomiting
• diarrhea
• abnormal liver function, as shown by elevated liver enzymes in blood tests

Chronic GVHD occurs on average about six months after a stem cell transplant. Often, this disease resembles autoimmune disorders that can happen outside of the transplant setting, such as Sicca Syndrome, lichen planus or scleroderma. 

Chronic GVHD can appear in many different ways and affect many different areas of the body. For instance, a patient might simultaneously have dry eyes, mouth ulcers, skin scarring, or other problems associated with the lungs, liver or genitals.

Can GVHD be prevented?

Multiple steps are taken to minimize the risk of GVHD. This includes selection of a donor that best matches the patient (meaning they share the same tissue proteins) and drugs designed to suppress the donor’s immune cells in the patient. But it’s important to remember that even with those drugs, GVHD can still occur. So, we’re actively looking at better ways to prevent it.

One of my colleagues, Rohtesh Mehta, M.D., is participating in a national clinical trial in which the donor stem cells are enriched with special cells called “regulatory (tolerizing) T-cells” as a method of preventing GVHD.

Another close collaborator, Robert Jenq, M.D., performs cutting-edge research studying the role of disruptions in the gut microbiome and the development of GVHD. Together, we’re developing trials to restore a healthy microbiome and prevent GVHD.

And, I’m chairing a very large national clinical trial that’s exploring whether giving patients with high-risk acute GVHD a serum protein called alpha-1 antitrypsin can resolve acute GVHD and improve survival when compared to standard treatment alone.

This is all really exciting stuff, and could change the whole paradigm for GVHD.

How does MD Anderson treat patients with GVHD right now?  

It varies from patient to patient, of course, because everyone is different. But GVHD can create chronic conditions that severely impact patients’ quality of life. So, our goal is to treat those symptoms, and restore our patients’ quality of life.

We’ve assembled a large, multidisciplinary GVHD team here at MD Anderson to do just that, with providers from virtually every department: dermatologists for skin disorders, pulmonologists for lung disorders, ophthalmologists for eye disorders, pelvic floor therapists for genital issues, and so on.

And all of these team members specialize in GVHD, so they’re familiar with how it manifests in each particular area. There are not many clinics like this in the United States.

What are the latest advances in the treatment of GVHD?

Two targeted therapy drugs were recently approved by the Food and Drug Administration (FDA) for the treatment of patients with chronic GVHD. One is KD-025, or belumosudil, and the other is ruxolitinib. Both are immune modulators that change the way T cells function, making them less inflammatory and more tolerant of tissue differences. Belumosudil also targets fibrosis, or scarring, pathways to reverse or halt this manifestation of GVHD.

We’re also studying a drug called itacitinib as an alternative treatment to steroids in patients identified as having low-risk acute GVHD, based on a blood test. Additionally, my colleagues, Partow Kebriaei, M.D., and Elizabeth Shpall, M.D., are conducting a cellular therapy clinical trial with umbilical cord-derived mesenchymal stem cells. It’s for patients with acute GVHD that has failed to respond to standard therapies.   

What’s the one thing you’d like patients to know about GVHD?

I’ve been caring for patients with GVHD for more than 20 years. And when I started out, no one wanted to do this type of research. At the time, there were no existing therapies to help patients get better. It was viewed as a lost cause.

Today, we have three different FDA-approved drugs available to treat patients with various forms of GVHD. And the field has evolved so much. Great advances are still happening.

Request an appointment at MD Anderson online or by calling 1-877-632-6789.