Research Corner

Both Siblings and Matched Donors are ALL in for Bone Marrow Transplants!

Authors: Ashlyn Jimenez & Becky Gold

          A few months ago we were introduced to the wonderful Hanna. As a quick update: Hanna received a bone marrow transplant on Friday, September 6th and is doing well. What a warrior she is!

          On a related note, our amazing LiveSmyle VP Yarenni recently had a birthday! This year, she decided to donate her birthday fundraiser to Hanna and her family, as Hanna herself is having a “birthday” — one that marks the start of her new and heathy bone marrow. If you are as inspired by Hanna and Yarenni as we are, check out the birthday fundraiser, where all proceeds go to Hanna and her family as they continue on this journey. (If you have trouble with that link, feel free to check out the Go Fund Me for Hanna and her family!)

          Since September is Childhood Cancer Awareness Month as well as Leukemia & Lymphoma Awareness Month, we wanted to circle back to Hanna’s original diagnosis and the most common type of childhood cancer, Acute Lymphoblastic Leukemia (ALL). Approximately 3 out of every 4 children who are diagnosed with leukemia are diagnosed with ALL, with most cases occurring in children between 2-4 years of age. About 3,000 individuals under age 20 are found to have ALL each year. 

          The treatment options for ALL are varied and will often include chemotherapy and immunotherapy. In fact, greater than 80% of children affected by ALL can be cured by chemotherapy. 

          Another treatment option available for the < 10% of patients with very high risk features or relapse, is hematopoietic stem cell transplantation (HSCT). HSCT comes from one of two donor pools: a matched donor or a sibling who is HLA-identical (more on HLA in a bit!). 

          This article examines a critical question: are outcomes for a patient with ALL who received HSCT comparable between a Matched Donor and an HLA-Identical Sibling? 

          Acute Lymphoblastic Leukemia is a cancer of the blood and bone marrow. It is due to an overgrowth of a specific branch of blood cells, called lymphoid stem cells. Normally, lymphoid stem cells will mature into one of three different kinds of white blood cells: 

  • B lymphocytes: these make antibodies to help fight infection. Early forms of B cells are the cells most commonly affected in ALL. 

  • T lymphocytes: these help B lymphocytes make the antibodies that help fight infection.

  • Natural killer cells: these attack and, you guessed it, kill cancer cells as well as virally infected cells.

          It is possible to get an overgrowth of the other branch of blood cells. The other branch produces cells called myeloid stem cells. Hence, an overgrowth of these cells is called Acute Myeloid Leukemia. 

          As mentioned earlier, chemotherapy is often curative for patients with ALL. Stem cell transplant is reserved for patients with high risk features or in patients that have relapsed. 

          First off, what exactly are stem cells and what makes them so special? Stem cells are unspecialized cells that have the potential to develop into multiple different types of cells, like a freshman college student who hasn’t decided their major yet. They also serve as an internal repair system and can divide indefinitely to replenish other cells that have reached the end of their lives. As they divide each new cell created also has the potential to either remain a stem cell or choose a different major and become another type of cell with a more specialized function, such as a red blood cell or a brain cell. Hematopoietic stem cells are a type of stem cell that can only differentiate into different types of blood cells — this is the type of stem cell used for ALL patients. They are found in bone marrow as well as in umbilical cord blood, and they have the ability to become the blood and immune cells mentioned above.

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          What makes transplants of hematopoietic stem cells difficult is finding a donor whose bone marrow “matches” the patient. Otherwise, patients are at increased risk for rejection of their transplant. It’s the same idea as blood typing — someone with blood type A- cannot donate to someone who is blood type B+. We all have certain proteins on our white blood cells called Human Leukocyte Antigens (HLA), and the more the HLA proteins are the same from donor to recipient, the better. If a cell displays an HLA that is “non-self”,  the body’s immune system sees this as an invader, which can result in transplant rejection.

          Before receiving a stem cell transplant, the patient will receive chemotherapy and radiation to kill the malfunctioning bone marrow. After transplant, the new stem cells find their way to the bone marrow and begin producing new, healthy cells. 

          This article looked at 138 children and adolescents who received HSCT from HLA-identical sibling donors, and 210 who underwent HSCT from matched donors. The 348 children from this study come from the 10 countries that were enrolled in the International-BFM ALL SCT 2007 prospective study to assess the impact of donor type in HSCT for pediatric ALL. The study ultimately found that outcomes of transplantation are comparable between a matched donor and an HLA-identical sibling. Overall, the four year event-free survival, overall survival, and non-relapse mortality were not significantly different between the two groups. 

          These findings could potentially allow physicians and patients to discuss expanding their donor options as appropriate. In many situations sibling matches are not available. This means that matched donors give patents larger groups of individuals to seek out HLA matches from, and therefore give these patients a better chance of survival.  

          One of the limitations to consider in this article is age difference in HLA-identical sibling donors and matched donors. In general, ALL is a disease of the young with children under the age of 5 having the greatest risk of developing ALL. Matched donors are usually consenting adults who volunteer to join a nonprofit database like Be the Match or Gift of Life. This means that sibling donors are usually much younger than matched donors, and the implications of this age difference are hard to explore. 

          Other considerations, particularly when the donors are young siblings, are the ramifications of bone marrow donation on the donor. Novels like My Sister's Keeper raise questions regarding the emotional toll on families and siblings in these trying situations. These challenges are worthy of moral and ethical exploration. 

          Knowing that these two options for bone marrow transplant are fairly equivalent in terms of outcome can give patients and families some peace of mind in the event that they are unable to attain HLA-matched bone marrow from a sibling and instead progress to a donor match. Of course, more research can always be done to mitigate any confounding factors or uncontrolled variables. In the meantime, consider supporting national bone marrow donor registries  like Be the Match or Gift of Life, volunteering time and resources to children's hospitals or cancer centers near you, and becoming an organ donor here. Let’s help give these patients a second chance at life.

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