Sickle cell disease has a relatively young history in the medical field. Scientists discovered it in 1910 and thoroughly studied it in the mid-20th century. For a century, the attempts of scientists have been treating the disease itself. However, blood-related complications have emerged linking the disease to leukemia in recent years. Researchers have been looking into this link, and a few candidates have come up. These candidates range from a person’s genetic makeup to the medications used to treat sickle cell disease. In this article, we will discuss these complications and current treatments. Furthermore, we will also be considering recent advancements in the disease’s treatment options that may reduce the risk of sickle cell disease complications.
How are sickle cell disease and leukemia related?
Before discussing the relationship between the two, it would be more appropriate to review each first. Sickle cell disease (SCD) is an inherited abnormality in red blood cells. Specifically, it is a defect in an oxygen-carrying protein in the blood called hemoglobin. This defect changes the form of the cell into a sickle shape, disrupting its function and life cycle, ultimately causing serious complications in the blood.
On the other hand, leukemia is an umbrella term for cancer of the blood. The type of leukemia a person could have depends on the component of the blood affected. The most common of the types include:
- Acute Lymphoblastic Leukemia (ALL): the bone marrow produces too much of a particular white blood cell.
- Chronic Myelogenous Leukemia (CLL): the bone marrow produces too many white blood cells.
- Acute Myeloid Leukemia (AML): the bone marrow produces too many immature and abnormal blood cells.
From this information, you may already be able to pick up the relationship between the two. Well, for one, both appear to be disorders in the blood. However, the most glaring connection can be found between SCD and AML. While SCD is an abnormality of the blood cells, AML is a disease that results from an abnormality. Although, it is not yet clear whether one is the result of the other. Let us try to clear things up with research.
What do studies show between sickle cell disease and leukemia?
Even as far back as the late 1990s, there have already been studies highlighting hematologic malignancies or leukemia related to SCD. Particularly, in a 1986 report, doctors studied four patients with SCD who later developed hematologic malignancies during their treatment. From this report, they raised the possibility of a link between SCD and leukemia due to certain chromosome alterations. Because of their findings, they asked for further epidemiologic and cytogenetic studies.
Fast forward to more than 30 years later, research between the links becomes clearer due to technological advancements in the field, especially in genomic studies. Additionally, due to these advancements, increased life expectancy in patients with SCD also increased the possibilities for cancer.
A retrospective cohort study in hospitals in England shows this increase in cancer risk among patients with SCD compared to those without SCD. In general, patients with SCD show higher rates of developing colon, non-melanoma skin, kidney, and thyroid cancer. The researchers observed an even higher rate of blood-related cancers, including Hodgkin’s and non-Hodgkin’s lymphoma, multiple myeloma, lymphoid leukemia, and myeloid leukemia.
In a separate cohort study performed in California, researchers also examined this increase in cancer risk between patients with SCD and patients without SCD. Contrary to the England study, patients with SCD had a 38% reduced risk of developing cancers associated with solid tumors such as breast, respiratory, urinary, and digestive cancers. However, the risk for leukemia increased twofold. Moreover, female patients and those aged 15-39 years old are three times as likely to develop leukemia. In addition, patients with severe SCD are four times more likely to develop leukemia.
Can we simply treat sickle cell disease to avoid acute myeloid leukemia?
The most prevalent treatment for SCD is through hydroxyurea. It is an FDA-approved drug used since 1998. Generally, hydroxyurea works by reforming sickle-shaped red blood cells back into their original shape. It helps prevent damage to the organs and relieve pain caused by these damages.
In a case study of a 26-year-old African-American woman published in 2019, complications arose during the hydroxyurea treatment of the patient. The patient developed AML after 26 months of hydroxyurea use as SCD treatment. The researcher looked into the patient’s genes and found treatment-related mutations in several locations in her genetic profile. This led the researchers to think that the patient’s development of AML could be a direct result of the hydroxyurea treatment.
While this specific case study can be against the use of hydroxyurea, the entirety of the medical field still has no conclusive evidence to avoid the use of the drug. However, scientists are already looking for alternatives against SCD that do not risk the development of AML.
Recent advancements in sickle cell disease treatment
Other than treatment through drugs such as hydroxyurea, scientists are also looking into alternative treatments such as stem cell transplantation. Stem cell transplantation involves the transfer of healthy donor stem cells to a patient with SCD. These healthy stem cells are important as they produce new cells that are not the abnormal blood cells due to SCD. While it is the only curative treatment for SCD, patients’ quality of life after treatment is not yet extensively known.
Another alternative treatment comes in the form of gene therapy. Substantial research is still being conducted as of 2018. However, human trials were already performed in 2017. The researchers utilized viral vectors to encode the human gene HBB variant βA-T87Q into a patient’s stem cells. The trial gained positive results as the patient no longer had SCD-related hospitalization after the treatment. However, doctors still require further research and trials to use the therapy in hospitals.
As previously mentioned, SCD is a relatively newly-discovered disease. However, research is more active now than ever. In the near future, two of these treatments may become available in the country.