World Cancer Day

Blood cancer is the commonest type of cancer in children. Blood cancers in children are, among many others, mainly of two types, acute lymphoblastic leukaemia and acute myeloid leukemia. Acute lymphoblastic leukemia is the commonest form blood cancer in children.

  For treatment purpose, children are divided based on age into infant leukemia (less than one year), childhood leukaemia (1-15yrs), adolescent and young adult 15-35 yrs. 

 Among these groups, best result is seen in 1-10yrs of age. And next best result is seen in adolescent group and worse results are seen in kids less than 6 months.

Incidence in India

According to GLOBOCAN estimates, there are nearly 25,000 children diagnosed with cancer in India every year and around 9000 of these have leukemia. Even with these conservative estimates, there would be 90,000 children with leukemia in a decade in India.

Cause of leukaemia.

Most of the case does not have any identifiable cause. Only a minority have a underlying genetic disease, which increases the risk for leukemia. These genetic diseases include Down syndrome, Li-Fraumeni syndrome, Ataxia telengiectasia etc.... Ionizing radiation may be a cause of leukemia rarely. (I think no need of describing the syndomes )

•             Genetic risk factors

Some genetic disorders increase a child’s risk of developing leukemia:

•             Down syndrome (trisomy 21): acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) than are other children, with an overall risk of about 2% to 3%.

•             Li-Fraumeni syndrome: a change in the TP53 gene. higher risk of developing several kinds of cancer, including leukemia, bone or soft tissue sarcomas, breast cancer, adrenal gland cancer, and brain tumours.

•             Other genetic disorders (such as neurofibromatosis and Fanconi anaemia) also carry an increased risk of leukemia,

•             Inherited immune system problems

Ataxia-telangiectasia

Wiskott-Aldrich syndrome

Bloom syndrome

Shwachman-Diamond syndrome

 Having a brother or sister with leukemia

 The risk is much higher among identical twins.

Signs and symptoms

In leukemia, all the three cell lines of bone marrow are altered and the symptoms are attributed to these alterations.

Symptoms from low red blood cell counts (anaemia):

Feeling tired (fatigue)

Feeling weak

Feeling cold

Feeling dizzy or lightheaded

Shortness of breath

Paler skin

Symptoms from a lack of normal white blood cells:

Frequent Infections

Fever

Symptoms from low blood platelet counts:

Easy bruising and bleeding

Frequent or severe nosebleeds

Bleeding gums

Bone or joint pain: This pain is caused by the build-up of leukemia cells near the surface of the bone or inside the joint.

Swelling of the abdomen (belly): because of enlargement of liver and spleen

Loss of appetite and weight loss

Swollen lymph nodes:

Coughing or trouble breathing:

Swelling of the face and arms – because of mass in chest which blocks the blood circulation

Headaches, seizures, vomiting: if cancer cells spread to brain

 Gums bleeding and gum swelling

Lab tests to diagnose and classify leukemia

Any alteration in the blood counts should raise the suspicion of acute leukemia. In these cases, peripheral smear examination by a pathologist might detect the leukemic cells (blasts) that warrant the referral to higher centers and further confirmatory tests. Certain genetic tests are also done which helps to risk stratify the patients and tailor the treatment accordingly in order to maximize the cure rates and minimize the side effects.

•             Complete blood picture

•             Flow cytometry

•             Bone marrow aspiration and biopsy

•             Molecular panel

•             Chromosomal analysis

Treatment

1.    Treatment of blood cancers are divided into different phases

a.    Induction :Aims to induce the complete remission and to restore the normal function of the marrow. Consists of intensified therapy and management of complications, mostly infectious and lasts for around 4 to 5 weeks.

b.   Consolidation :Aims to eradicate the residual leukemic cells that survived the induction phase and not detected by conventional methods.Consists of various risk adapted treatment regimens. Low risk patients are given less intense regimens and high risk patients are given high intense regimens, including hematopoietic stem cell transplantation.

 Maintenance :Aims to maintain the remission. Consists of oral chemotherapy drugs in low doses for longer duration of two to three years. This phase applies only to ALL

Chemotherapy protocol

Though different protocols are available, all the protocols essentially consist of similar drugs with minor variations in dosages and timings.

For treating blood cancer, there are different type’s protocols

1.            Indian protocols

2.            American protocols

3.            UK Protocols

4.            German protocols

Irrespective chemotherapy protocol used by doctor – results are same.

Cure rates

Acute lymphocytic leukemia (ALL)

The 5-year survival rate for children with ALL has greatly increased over time and is now about 70-90% overall.

Acute myelogenous leukemia (AML)

The overall 5-year survival rate for children with AML has also increased over time and is now in the range of 65% to 70%.

Latest developmentstreatment in blood cancers

The latest developments have been made in different areas including, understanding the biology of the disease, risk adapted protocols, refinement of the role of hematopoietic stem cell transplantation, methods to identify the minimal residual disease, development of targeted and immunotherapies and  improvement in supportive therapies.

Understanding the biology of the disease by certain genetic tests helps to identify the patients who are at high risk of relapse and can be treated be intensive regimens, including hematopoietic stem cell transplantation, thereby, improving the chances of cure. Conventional methods to identify the residual disease has some limitations and cannot identify the residual disease beyond a certain level. This residual disease which cannot be identified by these conventional methods is called minimal residual disease (MRD) and can be identified by employing novel methods. The role of MRD testing had been increasing involved in risk stratification and monitoring of the disease.

Development of targeted therapies and immunotherapy will improve the survivals.

High-dose Chemotherapy and Stem Cell Transplant for Childhood Leukemia

Targeted Therapy Drugs for Childhood Leukemia

•      Targeted drugs known as tyrosine kinase inhibitors (TKIs), such as imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna) attack cells that have the BCR-ABL gene mutation

•     Gemtuzumabozogamicin (Mylotarg) for AML Immunotherapy for Childhood Leukemia

•      Chimeric antigen receptor (CAR) T – cell therapy

For this treatment, immune cells called T cells are removed from the child’s blood and genetically altered in the lab to have specific receptors (called chimeric antigen receptors, or CARs) on their surface. These receptors can attach to proteins on leukemia cells. The T cells are then multiplied in the lab and given back into the child’s blood, where they can seek out the leukemia cells and attack them.

•     Tisagenlecleucel (Kymriah)

This is a type of CAR T-cell therapy that targets the CD19 protein on certain leukemia cells.

Monoclonal antibodies

•      Blinatumomab (Blincyto)

a monoclonal antibody which binds to two special cells at the same time CD 19 on B cells and CD 3 on T cells and attacks cencer cells

Social and family support:

Emotional support from the parents and other family members has a great impact on the recovery of the patients. Parents must provide their children a balance between the desires of the childhood and strict precautions the leukaemia and its treatment warrant

Survivorship:

As the cures rates of acute leukaemia’s in children have improving, the current focus is on survivorship. Cancer survivorship deals with making the patients and his/her parents to understand the treatment received, possible side effects and the ways to prevent or deal with them, possible chances of relapse and the means to prevent and identify them, rehabilitation, vocational training, employment, marriage, fertility, health insurance etc. Survivorship aims to improve the capabilities of a cancer survivor close to a normal individual.