Childhood Acute Lymphoblastic Leukaemia (ALL) - Diagnosis & Treatment

How is childhood acute lymphoblastic leukaemia (ALL) diagnosed?

A physical examination will first be conducted to check for swellings to see if any major organs are affected.

In addition, these tests may be required:

• Blood tests. The test involves taking a blood sample for a full blood count of red blood cells, white blood cells and platelets. The cells will be examined under a microscope. In most cases, a diagnosis of ALL can be made from direct examination of the blood cells.
• Bone marrow aspiration. Your doctor will take a small sample of bone marrow from the hip bone for laboratory tests. Examination of the cells under the microscope will help to confirm the diagnosis of ALL. Additional tests will also be carried out from the bone marrow samples:
  • Immunophenotyping. This is an examination of the immune outfit of the leukaemia cells. The results provide the ultimate diagnosis and single out ALL from other diagnoses such as acute myeloid leukaemia and acute mixed lineage leukaemia that may looks exactly like ALL under the microscope.
  • Oncogene fusion transcripts. Tests that target certain important genetic aberrations in the leukaemia cells can provide important information that is predictive of treatment responses and outcomes.
  • Cytogenetics. Chromosome re-arrangements and changes from the leukaemia cells can also provide information that can predict treatment responses and outcomes.
  • T-cell receptor and Immunoglobulin H-chain re-arrangements. Each child’s ALL comes with a specific genetic change that can be found in the T-cell receptor gene and/or the immunoglobulin heavy chain gene. By tracking the specific mutation, the amount of leukaemia cells remaining in the bone marrow after treatment can be measured. Minimal or measurable residual disease (MRD) monitoring is one of the most powerful way of treatment assessment to improve the outcomes of children with ALL.
  • RNA sequencing. The use of next generation sequencing to describe the genetic landscape within the leukaemia cell genetic mapping is the latest technology to sub-divide childhood ALL into different groups. This new grouping of ALL can provide new and accurate perspectives in the selection of the best treatment or treatment combinations. Hence, every child can receive personalised treatment for their best interest.
• Cerebrospinal fluid (CSF) examination. Your doctor will collect a small sample of the fluid that circulate in the central nervous system in a procedure known as lumbar puncture. This is to test for the presence of leukaemia inside the brain. The result will be used to plan for the right treatment.

How is acute lymphoblastic leukaemia (ALL) treated?

The contemporary treatment of childhood ALL is dynamic and highly personalised. Your doctor will suggest a treatment plan based on the initial immunophenotype of the ALL, and later findings from the oncogene fusion transcripts, cytogenetics, and RNA sequencing.

In addition, treatment modification may be required from time to time according to the results of minimal residual disease measurements.

Phases of ALL treatment

Treatment of childhood ALL is usually done in 2 phases:

• An initial intensive phase also known as the 'induction and consolidation treatment', aims to rapidly reduce the leukaemia cells in the body. Once the leukaemia becomes undetectable, the status is kwown as 'complete remission'. This intensive phase of treatment spans the first 7 months in most cases.
• A later maintenance phase that involves mostly oral chemotherapy to stop the leukaemia from returning. The maintenance phase will span about 17 months after the initial intensive phase of treatment. Most children’s lives go back to normal during this phase even though they are taking chemotherapy by mouth.

Types of ALL treatment

• Chemotherapy. Chemotherapy drugs remain the most powerful treatment for ALL in children. These are given in different combinations at different times by different ways.
  • Oral chemotherapy: Corticosteroid drug, 6-mercaptopurine, and methotrexate can be given by mouth
  • Intravenous injections: Direct injections or infusions into the bloodstream
  • Subcutaneous injections: Direct injections under the skin
  • Intrathecal (spinal) injections: Chemotherapy injections for the protection of the central nervous system against leukaemia infiltration

Chemotherapy alone with contemporary regimens can cure 70 – 90% of children with ALL in countries with advanced medical care.

The following treatment options are only reserved for special, complicated, or relapsed cases:

• Radiation therapy. Radiotherapy to the cranium used to be the main treatment in preventing the central nervous system from leukaemia infiltration. It is now replaced by intrathecal injections. Cranial radiotherapy is now only used in children with central nervous system leukaemia that does not respond well to chemotherapy.
• Haematopoietic stem cell transplantation. Children with ALL generally do not require a stem cell transplant. Stem cell transplant is necessary only if the leukaemia cells carry certain molecular changes or unfavourable genomic landscapes, or when the disease does not respond well to chemotherapy when measured by MRD. It may also be recommended if there is a relapse after treatment.
• Bispecific T-cell engager antibody therapy. These are synthetic antibody treatment that target certain types of B-cell ALL. This is often used after leukaemia relapse to bring the disease into complete remission faster.
• Chimeric antigen receptor (CAR) T-cell therapy. The patient’s own T-cells can be collected and genetically engineered to become killer cells for his or her own leukaemia. The current technology is used for patients with certain B-cell ALL although application for a wider variety of leukaemias may be possible in the future. CAR T-cell therapy is currently licensed for the treatment of relapsed B-cell ALL in children who have failed stem cell transplantation or other specific leukaemia treatment.