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The curious case of blood cancers and their treatment breakthroughs

To mark Blood Cancer Awareness Month in September, we examine the disease and how advocacy and research has led to better treatment outcomes for many patients.

 

Conceptual image of leukaemia cells being destroyed (Credit: iStock)

Many types of blood cancers

Blood cancers affect cells in the blood or bone marrow such as white blood cells, cells of the lymphatic system and plasma cells. They vary in how prevalent they are, how treatable they can be and who they affect.   

Leukaemia is the most commonly known type of blood cancer. It typically affects white blood cells in the bone marrow, causing them to divide too quickly and eventually crowd out other cells. There are four main types of leukaemia, acute myeloid leukaemia, acute lymphocytic leukaemia, chronic myeloid leukaemia and chronic lymphocytic leukaemia.  Acute lymphocytic leukaemia is more common in children, while the others are more commonly diagnosed in adults.

Lymphoma is another type of blood disorder that is broadly categorised into Hodgkin and non-Hodgkin lymphoma. Both Hodgkin and Non-Hodgkin lymphoma are cancers that affect lymphocytes, cells that make up the body's lymphatic system, which is a crucial part of the immune system. In lymphoma, lymphocytes multiply uncontrollably and cause swelling in the lymph nodes. Large cancerous cells called Reed-Sternberg are hallmarks of Hodgkin lymphoma disease but are not found in non-Hodgkin lymphoma. Hodgkin lymphoma makes up 10% of all lymphoma cases and is highly curable, while non-Hodgkin lymphoma is more common and unfortunately, harder to treat. Non-Hodgkin lymphoma forms in B cells or T cells of the immune system, with diffuse large B-cell lymphoma being the most aggressive form of the disease.

Myeloma, sometimes known as multiple myeloma, is a cancer of the plasma cells, a type of white blood cell in the bone marrow that protects us from infection.

Efforts to improve outcomes for blood cancer patients

While blood cancers are complicated and wide-ranging, a lot of effort has been put in over the years to better understand, diagnose, stage and treat these diseases, which has led to significant improvements in treatment outcomes.

After Sir Thomas Hodgkin first reported a group of patients with enlarged lymph nodes and spleens in 1832, research by multiple individuals led to advancements in radiotherapy for Hodgkin lymphoma treatment in the 1930s to 1950s. Following this, a team at the American National Cancer Institute used a novel combination of four chemotherapy drugs known as the MOPP regime, which reported the first documented cure of lymphoma in 1964. In the 1970s and 1980s, efforts began to develop more effective and less toxic treatments for both Hodgkin and Non-Hodgkin lymphoma. Combining lower dose radiotherapy and less toxic chemotherapy was found to result in cure rates of almost 90% of early-stage disease. To further boost this positive development, positron-mission-tomography (PET) scans introduced in the 2000s, were performed early in treatment to help predict the efficacy of chemotherapy drugs, allowing for more individualised treatment plans. Today, children and adults routinely survive a lymphoma diagnosis, and research and trials continue with the aim of developing less invasive cures and improving post-treatment quality of life.

Another success story is the most common childhood cancer, acute lymphocytic leukaemia. In the 1950s, famed pathologist, Sidney Farber found that folic acid stimulated the growth of blood and cancer cells and tried treating patients with aminopterin, an antagonist of folic acid, instead. This produced temporary remission in patients and was a significant breakthrough that laid the groundwork for advances in treatment for the disease. Since then, increased efforts in research, using new technologies such as cytogenetics to predict prognosis and individualising chemotherapy dosage have led to a cure rate of approximately 80% for acute lymphocytic leukaemia patients.

The situation in Singapore today

As with all cancers, there has been a steady increase in patients with blood cancers in Singapore. Between 2015-2019, lymphoma was the fifth most common cancer for men and women locally. And there was an increase of 1.9 cases per 100,000 population among males and 2.5 per 100,000 population among females in the 2015 to 2019 time period compared to the previous five-year period. Lymphoma was also the most commonly diagnosed cancer for men and women below 30 years old.  A similar increase in the incidence of leukaemia and myeloma was also observed.

While this may seem alarming, success in treating blood cancers and improving outcomes for patients is reassuring. The drive to individualise the treatment of blood cancers is fast becoming the strategy to deliver even better care and treatment. This approach requires carefully examining each patient's cancer based on several factors specific to that individual and their cancer.

One example is CAR-T cell therapy, an immune-based treatment that trains the patient's cells to recognise and fight cancer cells. They are made by collecting T-cells, a type of lymphocyte, from a patient and re-engineering them in the lab to produce proteins on their surface called chimeric antigen receptors or CARs. These proteins are expanded in the laboratory and infused into the patient, where they can then recognise the cancer cells and kill them.

In Singapore, acute lymphocytic leukaemia and diffuse large B-cell lymphoma patients have received CAR-T Cell therapy in clinical trials, and it was made commercially available to patients who need it in October 2021. Now patients with blood cancers and disorders can benefit from the therapy if they have failed to respond to other standard treatments.

As we celebrate Blood Cancer Awareness Month, we acknowledge the many efforts of clinicians, researchers and clinician-scientists who have rode on the momentum of past discoveries and successes to bring new hope. Long may their successes continue to benefit even more patients!    

Translating research to clinical reality at the SingHealth Duke-NUS Cell Therapy Centre (SDCT) and SingHealth Duke-NUS Regenerative Medicine Institute of Singapore (REMEDIS) Cell Therapy Conference 2022 Opening Ceremony. Clockwise, from top left: SDCT Head Professor William Hwang, GOH and Singapore Ministry of Health Deputy Secretary (Technology) Dr Cheong Wei Yang, SDCT Deputy Head Professor Jodhbir Mehta, REMEDIS Director Professor Teh Bin Tean and SDCT Principal Lead for Education Assistant Professor Francesca Lim

This June 2022, the SingHealth Duke-NUS Cell Therapy Centre (SDCT) and SingHealth Duke-NUS Regenerative Medicine Institute of Singapore (REMEDIS) held their second annual Cell Therapy Conference in Singapore. Themed "Translating to Clinical Reality", the two-day virtual conference brought together over 600 participants from healthcare, research and industry to learn the latest cell and regenerative therapy advances.

With updates about CAR-T cell therapy and sharing of other treatments being developed, the SDCT-REMEDIS Cell Therapy Conference 2022 provides an opportunity for clinicians, clinician-scientists and industry experts to foster collaborations and further develop the cell therapy and regenerative medicine ecosystem in Singapore.


References:

  1. American Society of Hematology. (2008). 50 Years in Hematology. American Society of Hematology. 
  2. Car T cells: Engineering immune cells to treat cancer. National Cancer Institute. (n.d.). Retrieved June 5, 2022, from https://www.cancer.gov/about-cancer/treatment/research/car-t-cells 
  3. Lakhtakia, R., & Burney, I. (2015). A Historical Tale of Two Lymphomas: Part I: Hodgkin lymphoma. Sultan Qaboos University medical journal, 15(2), e202–e206.
  4. National Registry of Diseases Office. (2022, January). Singapore Cancer Registry Annual Report 2019. https://www.nrdo.gov.sg/docs/librariesprovider3/default-document-library/scr-2019_annual-report_final.pdf?sfvrsn=fa847590_0