Will clinicians soon be able to have an upper hand in managing blood cancer?

As September is blood cancer awareness month, Dr Pradeep Mahajan, regenerative medicine researcher, reviews advances like hematopoietic stem cell/marrow transplantation which according to him, will soon allow clinicians to gain an upper hand in managing dreaded disease like leukaemia and lymphoma, enabling patients to lead a complete life

#FightBloodCancer is the hashtag used by the Leukemia and Lymphoma Society (US) to raise awareness about blood cancer and promote further support. September is blood cancer awareness month, and we need to understand the impact that these cancers have on individuals and families, and why it is essential to promote awareness and marrow donation campaigns.

In the USA, someone is detected with leukaemia, lymphoma, or other forms of hematological (blood-related) cancer every four minutes! Our own country India ranks 3^rd globally in the number of blood cancer cases reported. As of 2019, statistics revealed that India had approximately 8 lakh new cases of cancer per year, with lymphomas being the most common (64 per cent). Leukaemias have to been reported to account for 25 per cent of the total cases, while myeloma comprises approximately 11 per cent.

Unfortunately, blood cancers are the most common malignancies in children, adolescents, and young adults under 20 years of age. The burden of hematological cancers, especially when diagnosed in children can have far-reaching consequences. It is time to act on methods to enable such patients lead a healthier life, and reduce the financial burden and psychological stress on patients/families.

This is possible through ramping up early and routine screening programmes and therapeutics. Unfortunately, despite advances, there is no specific screening test to detect blood cancers prior to appearance of symptoms. However, research is ongoing and the possible ways to screen patients could be by identification of causative factors such as exposure to toxic compounds/heavy metals, adverse habits such as smoking and alcohol drinking, etc. Moreover, it would be beneficial if governments could set up health databases of families to identify genetic/hereditary factors.

Family physicians play an important role in keeping track of such cases. Key signs and symptoms to look out for are sudden unexplained weight loss, loss of appetite, unexplained fatigue following routine activities, pale skin, and bone pain, among others. Healthcare professionals could look out for enlarged lymph nodes, abnormalities in routine hematological investigations, enlarged liver/spleen, etc. As required, CT scan/PET scan, biopsy, lumbar puncture, etc. may be indicated to diagnose the malignancy.

From a therapy point of view, hematopoietic stem cell/marrow transplantation (HSCT/marrow transplantation) has been indicated for the treatment of blood cancer. The very first HSCT was performed in the year 1957, and currently this cell transplantation is one of the unique procedures in medicine. Broadly, there are two types of HSCT namely autologous, wherein patients donate their own marrow cells and allogeneic, wherein the patient receives the cell graft from a healthy donor. Although the process of matching donor and recipient cells is a complicated procedure, with certain side effects as well, as many as 42 per cent cases of blood cancer are treated by allogeneic HSCT.

To shed some light on what HSCT is, we need to understand that our blood has different cells-white and red blood cells and platelets. These cells function to fight infections, transport oxygen throughout the body, and in blood clotting. There are other cells as well (including different stem cells), all of which function to maintain balance of the circulatory system of the body.

Now, in blood cancer, as the name suggests, there are issues in production and functioning of these blood cells. As we know that blood circulates throughout the body, any problems in these cells will lead to circulation of dysfunctional cells. These cells will then not be able to perform their functions efficiently leading to the myriad of symptoms seen in cancer patients.

With marrow transplantation, the environment of the bone marrow (the area in bones where the blood-forming cells are produced) can be modified. However, in order to “clear the path” for healthy cells, chemotherapy and/or radiation therapy is indicated to eradicate preexisting cancer cells. With a cleaner environment for the donor’s stem cells, the transplantation procedure is performed, followed by other standard cancer care protocols.

The advantage is that through this HSCT, as the cancerous cells are eliminated, patients tend to be free of symptoms for longer periods than conventional pharmacological/radiation treatments. HSCT has also been reported to prolong the overall survival and recurrence rates of blood cancers.

The need of the hour therefore is to create more awareness regarding donation of HSCs/marrow. Typically, the donation process is a day-care procedure; however, donors may be hospitalised overnight to monitor their general condition. Donors need not worry about “losing” their own stem cells after donation. Typically, the median time reported for full recovery after marrow donation is 20 days. The marrow is like a factory, the cells are formed continuously. Self-renewal is a characteristic of stem cells. Therefore, there are no lasting side effects in donors.

The minor side effects that may arise are associated with pain at the site where the cells are harvested from (usually hip region), fatigue, and weakness that last for 1-3 days after the procedure. Anesthesia-related side effects of nausea and vomiting may occur, but these are managed with medications soon after the harvesting procedure.

In all, HSCT/marrow transplantation is an effective therapeutic procedure and donating the same is a noble act towards saving a cancer patient’s life. Of course, no procedure is foolproof or 100 per cent effective. There are side effects associated with allogeneic HSCT; however, there are management strategies to tackle these. Moreover, there are more advanced and allied forms of regenerative medicine and immunotherapy being researched and implemented, either as stand-alone or combination therapies. Dendritic cell (DC) vaccines, natural killer (NK) cell therapy, monoclonal antibodies etc. are some of the other advances in cancer care.

To understand about these advances, we need to first know about what our immune system does. Immune surveillance by multiple cells in our body is responsible for recognising and eliminating damaged/abnormal cells, thereby protecting the host. What happens in cancer is that the immune system is challenged to keep the uncontrolled proliferation of cells in check. Additionally, cancer cells are capable of ‘hiding’ from the immune system and evade being removed from the body. In other instances, despite recognition of the abnormality, rapid proliferation and substances released by cancer cells may hinder immune surveillance. Thus, the aforementioned recent advances in cancer therapy aim to harness the power of immune cells and train them to specifically attack cancerous cells.

DCs are professional antigen presenting cells that act as a bridge between the innate and adaptive immune systems. DCs are responsible for the initiation and regulation of adaptive immune responses to viruses, bacteria and tumors. In context of blood cancers, DC therapy has been found to be beneficial at later stages (following chemotherapy or HSCT) in delaying relapse. The overall survival of patients was found to increase when patients under remission were administered DC vaccine.

Likewise, NK cells are components of the innate immune system that play a major role in host-rejection of tumors and virally infected cells. NK cells can kill target cells/cancer cells without prior immunisation or Major Histocompatibility Complex restriction. Therefore, immunotherapy strategies aim to utilise adoptive transfer of expanded NK cells to inactivate cancer cells. Studies have supported the fact that NK cell-mediated immunosurveillance can be the key to attaining durable remissions in patients with myeloid malignancies. There are other immune cells, such as T cells/CAR-T cell therapy as well, which are being researched either as standalone therapies or in combination to target hematological malignancies.

Talking a bit about the equipment and machinery used in this field, there are now systems which enables magnetic separation of the desired population of cells in an automated manner. Some of these devices offer advanced integrated solutions to streamline cell processing workflows – from cell separation through cell culture to formulation of the final product. For example, a particular platform enables the entire workflow for the manufacture of CAR T cells, from T cell selection and activation, to viral transduction, and cell expansion.

The final product is harvested in the desired buffer and is then ready for cryopreservation or direct infusion. The system has applications for DC and NK cells, as well. The process is rapid and reproducible that provides GMP-compliant cells/cell products. Why this is beneficial is that, the waiting time and the worry regarding a source of high-grade cell products are eliminated.

Taken together, through these advances, we will soon be able to have an upper hand in managing this dreaded disease and enable our patients to lead a complete life. We are living in an ever-evolving society and medical science is reaching new heights. To be able to give back to the community and the society is a blessing and to enable blood cancer patients, especially little children, live life in a healthier manner through natural treatments such as HSC/marrow donation is the highest level of kindness.