What is Blood Cancer?

Due to India's  diverse inhabitants and variations in regional development, genetics, environments, and lifestyles, the distribution of blood cancer across the country is heterogeneous. Leukaemia is the sixth most prevalent malignancy between 1990 and 2019 (excluding other neoplasms), making up around 6.79% of all malignancies. 

According to the Indian Council of Medical Research (ICMR), blood cancers account for 8.2% of all cancers in India, with an incidence rate of 5.5 cases per 100,000 population per year. Approximately 80,000 new cases are detected annually, and the ICMR-National Centre for Disease Informatics & Research (NCDIR) tracks these statistics through its National Cancer Registry Programme. 

What is Blood Cancer?

Most blood cancers, referred as hematologic malignancies or Blood and Bone Marrow cancers, originate in the bone marrow, where blood cells are produced. The bone marrow produce stem cells that mature and become one of the following:

• Red blood cells which carry oxygen across the body.
• White blood cells which fight infection.
• Platelets that control bleeding.

Like in all cancers, blood cancers occur when abnormal blood cells grow uncontrolled and interfere with the function of normal blood cells which fights infection and produce new blood cells.

Types of blood Cancers

There are three main types of blood and bone marrow cancer

• Leukaemia - arising from immature white blood cells (leucocytes)
• Lymphoma - arising from Lymphocytes
• Myeloma - arising from Plasma cells.

Leukaemia:

Leukaemia is caused by the rapid production of abnormal white blood cells which affects the ability of the bone marrow to produce red blood cells, and platelets. Based on the progression and the type of cell that is affects, Leukaemia is classified into the following:

• Acute Lymphocytic Leukaemia (ALL)
• Acute Myelogenous Leukaemia (AML)
• Chronic Lymphocytic Leukaemia (CLL)
• Chronic Myelogenous Leukaemia (CML)

Leukaemia can occur in both adults and children, ALL followed by AML are the most common in children, whereas adults are more prone to AML and CML types.

Lymphoma

Lymphoma is a cancer of the lymphatic system, an important part of the body's immune system. The Lymphatic system also plays a role in maintaining healthy fluid levels in the body, removing cellular debris and harmful substances from the tissues, and helping the body absorb certain fats and other molecules.

Lymphoma is classified under two broad categories:

• Non-Hodgkins lymphoma.
• Hodgkins Lymphoma

Recurrent Blood Cancer

Recurrence of blood cancer typical means a comeback of the already existing cancer cells post-treatment of a patient. The period after which such a recurrence can happen is indefinite. If one has been exposed to cancer cells once it may mean it can happen again, within days, weeks, months, or maybe years later.

Leukaemia recurs in two cases:

• Induction failures are patients who fail to achieve an initial complete disappearance or remission of their cancer following two or more courses of remission induction chemotherapy
• Patients who achieve a complete remission to initial treatment and then experience a cancer recurrence have relapsed leukaemia. Relapse of Leukaemia may occur several months to years after the initial remission; However, the majority of relapses occur within 2 years of initial treatment.

Treatment Options For a Recurrence :

If cancer recurrence or remission does not happen in the treatments, a patient has two options. Since continuing the existing treatment may rarely have a positive effect.

• A palliative approach can be adopted, where drugs are administered in non-toxic doses to keep the disease under control for as long as possible. The emphasis is on the quality of life and supportive care measures in such a case.
• Another approach is to receive more intensive treatment in an attempt to produce a complete remission.

There are two intensive strategies for the same:

• A bone marrow or blood stem cell transplant offers a possibility for control or cure of leukaemia, which for younger patients.
• To participate in clinical trials evaluating new treatments.

Causes For Blood Cancers:

Certain factors play a role in increasing the risk of blood cancer such as:

• The risk increases as people grow older people.
• Blood cancers are more common in males.
• Smoking history or exposure to second-hand smoke may increase risk.
• Long-term exposure to benzene and formaldehyde (people who work in industryes like manufacturing) can increase risk.
• Patients who have received chemotherapy or radiation in the past.
• Some blood cancers are familial in nature.
• Several autoimmune diseases, conditions that cause long-term inflammation and some genetic disorders are associated with increased blood cancer risk.

Symptoms of Blood Cancer

The symptoms of blood cancer may often be ignored or overlooked. This is because they are nonspecific and can be usually explained by flu or other common illnesses. But one must consult a doctor if any of the symptoms persist, and early diagnosis of blood cancer is essential for recovery.

The symptoms of blood cancer are because of the imbalance in the volumes of different types of blood cells. The manifestation of these symptoms depends on the type of blood cancer, the stage of cancer in the person, the progression (acute or chronic), and even differs from person to person.

• Anaemia
• Thrombocytopenia
• Swelling of Lymph nodes
• Unexplained weight loss
• Swelling of liver or spleen
• Fever or infections
• Pain in the bone
• Night sweats

Screening and Diagnosis:

There are no recommended screening tests for blood cancers. However, some of the common tests done for blood cancers are as follows:

Complete blood count

This blood test measures the concentration of various types of blood cells-red blood cells, white blood cells and platelet cell count, in the given sample. Any abnormalities in the blood cells or their concentration can be determined using this test. Bone marrow biopsy may help in confirming this diagnosis.

Bone marrow biopsy/aspiration

Removal of bone marrow sample for testing is called bone marrow biopsy or aspiration, the difference being the follows:

• Bone marrow aspiration: Extracting a liquid bone marrow sample.
• Bone marrow biopsy: Removing a small amount of bone marrow tissue.

It is used to determine if the cancer is affecting the bone marrow, the type of blood cancer, the stage or severity of the disease. Changes in blood cells that are not detected in complete blood count can be detected using this test.

Both the tests are performed at the same time under medical surveillance. The main purpose of this test is to confirm blood cancers and bone marrow disorders, detect any DNA abnormalities in the sample. Post anticancer treatments, this is used to check the progress of the treatment and evaluate the patient's tolerance.

Lymph Node biopsy

Blood cancer affects the blood cells which in turn means that the immune system completely gets affected. The lymphatic system is responsible for the human immunity. It includes tonsils, spleen and lymph nodes. The lymph nodes are present in hundreds in the body which contain white blood cells to fight infections.

In lymph node biopsy, a small cut is made and the node is taken, and the cut is closed by stitches. This gives information about the blood cancer, its type, stage and spreading.

Spinal tap

It is also referred as lumbar puncture. A fine needle is inserted in the space between between the bones in the lower back and cerebrospinal fluid is extracted from the spine. This fluid is examined under a microscope to see if the blood cancer has spread to the spinal cord.

Flow cytometry

This test determines the blood and bone marrow cells to analyze a change in the white blood cell count that could cause cancer. An instrument known as flow cytometer is used to measure the number and percentage of cells and their characteristics. This test also helps to detect the residual levels of cancer post treatment. The results are also useful for measuring the amount of DNA in the blood cells.

Karyotype test

This test maps the 46 human chromosomes of a cell to determine the changes in the chromosomes and their arrangement. G-banding is the method used for this test. A stain called Giemsa is used to make the banding pattern of chromosome pairs easier to see. This test looks for abnormalities in the size, shape, number and arrangement of the blood cells or bone marrow cells. This test can help the doctor prescribe the medications and plan the treatment.

Diagnosing recurrent cancer:

A formal follow up plan is given to any patient who has undergone cancer treatment. This plan includes a schedule for visits to the doctor, careful physical examinations, and possibly other tests. These visits and tests are essential to make sure you are healthy and to watch for a recurrence.

Treatment

The treatment for blood cancer depends on the type and stage of cancer, age of the patient, the organs involved by cancer, tolerance of the patient among other factors.

The most important treatments for curing blood cancer are:

Chemotherapy Treatment

Chemotherapy for blood cancer is a form of chemical drug therapy that aims to destroy the rapidly growing cells in the body. It is a primary treatment modality for blood cancer. Chemotherapy can either control or cure the disease.

Radiation Therapy Treatment

Radiation therapy (Radiotherapy) for blood cancer uses high energy radiation to kill the cancer cells. The therapy works by damaging the DNA in the cells, which restricts their growth and reproduction.

External Beam Radiation is the preferred technique for the treatment of blood cancers.

Total body irradiation (TBI) is a form of external radiation where the entire body, is irradiated to prepare a patient for a stem cell transplant by destroying cancer cells, creating space in the bone marrow for new stem cells, and suppressing the immune system to prevent rejection of the new cells.

Total Marrow and Lymphoid Irradiation (TMLI) is an advanced radiotherapy technique that delivers high-dose radiation to the bone marrow and lymph node chains, while sparing organs like the heart, lungs, and kidneys, to provide immunosuppression for hematopoietic cell transplantation. It is used as part of a conditioning regimen before stem cell transplantation, particularly for acute lymphoblastic leukaemia (ALL) and haploidentical transplants, offering an alternative to total body irradiation (TBI) with potentially reduced toxicity. TMLI uses intensity-modulated radiotherapy (IMRT) or other techniques to target the bone marrow and lymphoid tissues, improving treatment outcomes and minimizing side effects such as organ damage

Stem Cell Transplantation Treatment For Blood Cancer

Stem cells are the cells of the bone marrow, these develop further to form different types of blood cells. When the blood cells are critically affected and the functioning of the body declines, the body needs more than getting rid of cancerous cells. So in addition to treatments aimed at destroying cancer, stem cell or bone marrow transplantation may be needed.

Procedure for Stem Cell Transplantation

Before a stem cell transplant, the patient is given a conditioning regime. This treatment involves the elimination of cancer cells in the body, for which the patient undergoes high levels of chemotherapy and in very few cases, radiotherapy as well under strict monitoring. This prepares the body for stem cell transplantation. The stem cells are injected through the veins. These cells travel across the blood and reach the bone marrow to make new blood cells. This procedure is referred as engraftment. The stem cell transplant procedure would generally take an hour.

Some of the common side Effects include:

• mouth and throat pain
• bleeding and transfusions
• interstitial pneumonitis
• nausea and Vomiting.

Post transplantation, the patient's blood count is monitored regularly. In some cases, the patient might require blood cells and platelet transfusion. Special and additional drugs are given in order to prevent infections and other issues in case the stem cells are extracted from donors.

Targeted Therapy

These therapies particularly target the specific molecules that help the cancer to grow and spread across the body. The main principle is to target the genes, proteins and supporting blood vessels. This treatment is used alone or as a combination with chemotherapy. Depending on the type of blood cancer and the characteristics of the cancer cells, the following are the major options

• Monoclonal Antibodies: Monoclonal antibodies are man-made versions of immune system proteins. These are designed to attach to the surface of the cancer cells. The main objective of these antibodies is to react to the cancer cells and help the immune system to destroy them. Monoclonal antibodies are given along with chemotherapy for chronic blood cancer. Some major side effects of this therapy include chest pain, heart racing, swelling, cough, trouble in breathing and severe dizziness.
• Tyrosine kinase inhibitors3: Tyrosine kinase inhibitors (TKIs) are targeted therapies that treat blood cancers like Chronic Myeloid Leukaemia (CML) by blocking the activity of specific proteins that promote cancer cell growth by stopping the function of abnormal cells. Examples of such medications include imatinib, dasatinib, and nilotinib. They stop the cancerous cells from replicating and dividing, leading to long-term remission or increased lifespan for patients
• Interferon: Generally, interferons are substances that are naturally produced in our body by the immune system. The therapy involves drugs that mimic this effect and was previously one of the most effective treatments. These drugs restrict the growth and division of blood cancer cells. The general treatment could continue for a few years. The patients have to deal with the side effects during the treatment, but they can cope-up easily post the therapy.

Common side effects of Targeted Therapy:

The generalised side effects of the targeted therapies are:

• Skin problems
• Problems with blood clotting and wound healing
• Increasing blood pressure
• Gastrointestinal perforation

Bone Marrow or Stem Cell transplantation

Bone marrow contains many Leukaemia cells, which makes autologous stem transplantation or high dose chemotherapy a rare option to patients who fail remission induction therapy; however, allogeneic stem cell transplant might work.

The patients with complete remission need autologous stem transplantation or high dose chemotherapy in most cases. However, this can only happen if the survivor has opted to store their stem cell collected at the initial remission. Stem cell collection after relapse is less successful since less than half of patients receiving reinduction chemotherapy achieve a second remission. Patients without previously stored stem cells, therefore, are often treated with allogeneic stem cell transplant or additional chemotherapy.

In these settings, allogeneic stem cell transplantation offers the only prospect of long-term disease-free survival. If a compatible family member donor or autologous stem cells are not available, there should be a search for an unrelated donor or an umbilical cord source of stem cells.

CAR-T cell Therapy:

It is a form of immunotherapy which are made from a patient's own T cells - body's primary killer of infected and other diseased cells. While CAR T-cell therapies may not work for everybody, in some with advanced cancer they can completely eradicate their disease, often for long periods of time.

Clinical trials

Clinical trials are research studies where people are involved in the test of the effectiveness of treatment. Through these, doctors find new ways to improve treatments and the quality of life for people with the disease.

Clinical trials are the final step in a long process of evolution of a certain kind of treatment which starts with lab research. However, few things need good thought before entering into any of such trials, like:

• The progress of the method
• The risk factors involved

Participating in clinical trials is crucial in the development of existing cancer treatments. All the types of treatment available today were clinical trials in the past. Participating in them may not only increase the chances of one's remission but also the evolution of a new treatment.

Survival Rate4,5,6,

Survival rates for blood cancer in India vary significantly based on the type of cancer, the specific medical center, and factors like the patient's financial resources and access to care. Among the childhood ALL, the 5 year survival in India ranges between 60% - 80%; for AML, the survical is higher among the children when compare to adults and the survival for Multiple Myeloma is over 80%. While precise, nation-wide, overall survival figures for all blood cancers in India are limited, data from major hospitals and collaborative studies provide some key insights:

References:

1. Nalage DN, Kudnar PS, Langhe R, Ughade B, Sontakke T, Biradar A. Leukaemia in India: Insights Into Incidence, Prevalence, Mortality, and Disability-Adjusted Life Years. Cureus. 2024 Jun 17;16(6):e62557. doi: 10.7759/cureus.62557. PMID: 39027787; PMCID: PMC11254514.
2. https://www.pib.gov.in/PressReleasePage.aspx?PRID=2102729#:~:text=Introduction,strengthen%20cancer%20care%20in%20India.
3. https://my.clevelandclinic.org/health/treatments/24984-tyrosine-kinase-inhibitors
4. https://ascopubs.org/doi/10.1200/GO.20.00625
5. https://www.manchester.ac.uk/about/news/indias-childhood-leukaemia/#:~:text=Work%20led%20by%20Professor%20Vaskar,thanks%20to%20his%20revolutionary%20approach.
6. Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA, Lakshmi KM, Sitaram U, Abubacker FN, Abraham A, Viswabandya A, Srivastava VM, Srivastava A, Balasubramanian P, Mathews V. Acute myeloid leukaemia: challenges and real world data from India. Br J Haematol. 2015 Jul;170(1):110-7. doi: 10.1111/bjh.13406. Epub 2015 Apr 9. PMID: 25858293; PMCID: PMC4864448.