Haploidentical Stem Cell Transplantation

Overview

Being diagnosed with blood cancer or a blood condition can be a frightening experience for you and your family. To be fit and healthy, you need strong bone marrow and blood cells. A stem cell transplant may be your best therapy choice if you have a disorder that affects your bone marrow or blood. For some, it provides hope of a possible cure.

Hematopoietic stem cell transplantation from haploidentical donors is an appealing form of transplantation because of the quick availability of donors, the simplicity of stem cell procurement, and the opportunity to collect more donor cells for cellular treatment if necessary.

Hematopoietic stem cell transplantation

For patients with high risk or advanced hematologic malignancies, hematopoietic stem cell transplantation is the therapy of choice. Approximately 70% of patients, however, do not have a matched related donor available for transplant. Because of the comparable transplant results, a matched unrelated donor (MUD) transplant is chosen for these patients.

MUD transplants, on the other hand, are limited by the fact that only 50% to 60% of patients who require them have a matched donor, and the donor search and purchase of an unrelated donor hematopoietic stem cell product takes significantly longer than the usage of a related donor transplant (approximately three months). The most serious issue is that the likelihood of finding a MUD for a non-Caucasian individual differs greatly between ethnic minority groups.

Finding a matched unrelated donor (MUD) becomes even more difficult for mixed-race persons, who have a poor likelihood of finding a matched donor in the registries. In the United States, interracial/interethnic marriages are at an all-time high. According to 2010 U.S.  around 3% of the U.S. population identifies as mixed race, and the percentage of mixed race persons has grown by approximately 50% since 2000.

For such individuals, haploidentical stem cell transplantation (HaploSCT) is an alternate therapy option. Unless they were adopted, most people have a family (parents, children, or siblings) who matches in at least one human leukocyte antigen (HLA) haplotype. Demographic trends, at least in the United States, strongly highlight the need to further improve this type of transplant.

The use of mismatched related donors for transplantation offers the benefit of practically universal and quick availability of donor stem cells for transplantation, as well as the ability to collect more donor cells for cellular treatment if necessary. In this paper, we look at the past and future of haploidentical transplantation.

What is Haploidentical Stem Cell Transplantation?

A form of allogeneic transplant is a haploidentical transplant. A half-matched or partially-matched transplant is another name for it. The donor is just a partial match for the patient. It replaces the damaged cells with healthy, blood-forming cells from a half-matched donor. Typically, the donor is a family member.

For allogeneic transplants, your doctor will do a blood test to determine your human leukocyte antigen (HLA) type. HLA is a protein or marker  located on the majority of your body's cells. Doctors search for donor or umbilical cord blood that matches your HLA. However, there are situations when they are unable to discover a close HLA match. A haploidentical transplant may then be a possibility. This is an allogeneic transplant in which the donor matches precisely half of your HLA.

A haploidentical, or half-matched, donor is often your mother, father, or kid. Parents are seldom a complete fit for their offspring. Siblings (brothers and sisters) have a 50% probability of being a half-match. Other family members (such as cousins, aunts, or uncles) are unlikely to be a half-match.

To increase the number of prospective donors, researchers in the early 2000s devised a modified kind of stem cell transplant known as a haploidentical transplant, in which a healthy first-degree relative - a parent, sibling, or kid - may frequently serve as a donor. Instead of a near-complete HLA match, donors for a haploidentical transplant only need to be a 50% match to the recipient.

The method for a haploidentical transplant is similar to that of a conventional allogeneic transplant for both donors and recipients. The key distinction is that patients get a very high dosage of the chemotherapy medication Cytoxan many days following the transplant. This results in a significant decrease in activated T cells, which are important contributors to graft-versus-host disease (GVHD), a possible adverse effect of transplantation in which donor immune system cells assault the body.

Haploidentical transplants have similar success rates to conventional transplants. Because haploidentical transplants are a newer surgery, it's unclear if their anticancer impact will last for many years. A clinical trial run by the Blood Marrow Transplantation Clinical Trials Network comparing haploidentical stem cells to another source of partially matched donor cells - umbilical cord blood - in patients with specific kinds of leukemia and lymphoma may provide further clarity.

Who might need a haploidentical transplant?

Haploidentical transplants are becoming increasingly popular since they can aid in the rapid identification of a compatible donor. If no perfectly matched donor is discovered for your kind of blood cancer or blood disease, a haploidentical transplant may be an alternative. Your transplant team will make the best selection for your specific case.

Because there are more mismatches between you and your donor in a haploidentical transplant, you are more likely to experience post-transplant problems. However, with advancements in transplantation techniques and post-transplant care, they can be a viable option if you don't have an HLA-matched donor.

Unfortunately, haploidentical transplants are not acceptable for many patients and are not accessible in every institution, so discuss your choices with your transplant team.

What will happen before the transplant?

To your relative

If your relative is a good match and willing to give their stem cells, your transplant center will schedule a 'donor evaluation' and a medical check to ensure they are healthy enough to donate. 

To you

A conditioning treatment will be used to prepare your bone marrow and immune system for the new cells. It entails chemotherapy and, in some cases, a kind of radiotherapy known as whole-body irradiation (TBI). This also eliminates any leftover aberrant cells that are causing your disease.

What will happen during the transplant?

During your transplant, your medical team will inject fresh, healthy stem cells from a matched donor into your circulation. After some time, they will adhere to and develop within your bone marrow (a process known as engraftment) and begin to produce new blood cells.

If you require a stem cell transplant, every attempt is made to match you with a suitable donor. Your human leukocyte antigen (HLA) tissue type is used to match you. Your HLA is what makes you 'you' - it's part of your unique genetic make-up - but finding a perfect match isn't always achievable.

A haploidentical (commonly abbreviated to 'haplo') transplant using a family member whose tissue type is half-matched to yours is one option. Children are seldom a perfect match for their biological parents, and vice versa. Siblings are 50% likely to be a half-match for each other. This implies you have a larger pool of possible donors to choose from because practically everyone has at least one haploidentical match in their family.

Your transplant will usually take place the day after your conditioning treatment is completed. Your relative's stem cells will be sent in the form of a liquid in a tiny bag. They will be injected into your circulation through a tiny tube, exactly like a blood transfusion. The transplant is not unpleasant, and you will be awake the entire time because there is no surgery involved.

Recovering from a Haploidentical Transplant

You'll most likely be in the hospital for three to four weeks following your transplant. This period will be spent in safe isolation to allow your immune system to begin repairing itself. You'll be in your own room, with protections in place to limit your chances of contracting an illness. Your recuperation will most certainly have an impact on many elements of your life once you return home. It may take six to twelve months for your activity levels to recover to normal.

What side effects can I expect?

Transplantation is a highly demanding therapy that will have an impact on you both physically and emotionally. Your transplant team will discuss the risks of problems and side effects with you so that you may make the best decisions for your treatment.

Side effects vary from person to person and can be short or long-term.

Short-term side effects can include:

• Increased risk of infections
• Sore mouth (mucositis)
• Liver and kidney problems
• Tiredness
• Diarrhea and feeling or being sick
• Loss of appetite
• Hair loss.

You may feel gloomy at times and struggle to cope with your condition. It's understandable. Your transplant team will listen to your concerns and may be able to connect you to a therapist for more assistance.

Long-term side effects can include:

• Increased risk of infection
• Fatigue
• Graft versus host disease (GvHD).

There will be minor changes between your growing immune system and other cells in your body following your transplant. As a result, your new immune system may attack your own cells since they are perceived as 'different.' This is known as graft versus host disease (GvHD)

It can affect any region of your body, but it most commonly affects your skin, intestines, and liver. It might be moderate or severe, and it can be brief or long-term. Your transplant team will regularly monitor you for symptoms of GvHD and will provide you with medicines to help manage your immune system.

Making bone marrow transplant safe and available to all

For decades, graft versus host disease (GVHD) precluded bone marrow transplants from being conducted on patients who did not have a donor with a nearly perfectly matching immune system, generally a sibling or sister. Some of these patients were matched with unrelated donors through a huge national registry, but most became ill and died while waiting for a match. As a result, only roughly half of the patients qualified for the possibly curative treatment. Minorities were the hardest hit. African-American patients who did not have a familial match had a less than 10% probability of obtaining a donor in the unrelated registry.

Clinical trials revealed that when T cells were eliminated, patients did not develop GVHD, yet their malignancies occasionally returned. It was one of the first reports of the immune system's ability to eliminate cancer cells. The problem was to eliminate a specific number of T cells—enough to avoid the most severe cases of GVHD while still allowing the immune system to protect the cancer from returning.

It was discovered that the same medicine used to treat patients before to bone marrow transplant may be administered post-transplant to minimize GVHD without interfering with the T cells' capacity to sweep up any surviving cancer cells. This discovery inspired doctors at the Kimmel Cancer Center to create a novel form of bone marrow transplant known as a haploidentical or half-identical transplant.

With this ground-breaking method, practically all patients' parents, siblings, and children—and occasionally even aunts and uncles, nieces and nephews, half-siblings, and grandparents or grandchildren—can safely serve as donors. Almost every patient in need of a bone marrow transplant may now locate a suitable donor.

These clinical trials were so effective, with safety and toxicity levels equivalent to matched transplants, that the treatment is currently used to treat chronic but debilitating noncancerous blood illnesses in adults and children, including sickle cell anemia and severe autoimmune disorders.

Conclusion

For the approximately 70% of individuals who do not have an HLA-identical sibling donor, haploidentical stem cell transplantation is a therapy option. The availability of a haploidentical donor in most families is a potential benefit, both for reducing the need to obtain an unrelated donor and for inducing a possibly more robust graft-versus-tumor effect. Early problems of severe graft-versus-host disease (GVHD) after T-cell replete stem cell transplantation (SCT), as well as graft failure and recurring malignancy (after T-cell depletion SCT), have limited the uses of this method.