Paediatric CML

Caring for children and adolescents with CML brings unique challenges - from diagnosis and treatment through to long-term care and life beyond cancer. This dedicated hub brings together expert knowledge, clinical resources, and global insights to help improve care and outcomes for young people living with CML around the world.

What is Chronic Myeloid Leukemia (CML)?

Chronic myeloid leukemia (or myelogenous leukemia, CML), is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow and the accumulation of these cells in the blood.

CML is a bone marrow stem cell disorder. It is associated with a characteristic chromosomal translocation called the Philadelphia chromosome. In this translocation, parts of two chromosomes (the 9th and 22nd) switch places. As a result, part of the BCR ("breakpoint cluster region") gene from chromosome 22 is fused with the ABL gene on chromosome 9, creating the "fusion" gene BCR-ABL, called a tyrosine kinase.

The tyrosine kinase is continuously active and does not require activation by other cellular mechanisms which normally regulate the division of cells. This leads to an uncontrolled multiplication of blood cells. Moreover, the BCR-ABL protein inhibits the cells' DNA repair mechanisms, making the cell more susceptible to developing further genetic abnormalities.

With improved understanding of BCR-ABL, targeted therapies like imatinib, nilotinib and dasatinib have been developed. These specifically inhibit the activity of the BCR-ABL protein. These tyrosine kinase inhibitors are able to induce complete remissions in CML in about 80-90% of all patients treated in the first phase of the disease, the chronic phase.

What is so special about childhood CML?

In general, acute leukemias are most prevalent in children and are therefore often referred to as "childhood leukemias". The chronic forms of these leukemias, including Chronic Myeloid Leukemia (CML), are seen almost solely in adults. With the average age of diagnosis of CML being around 60 in western countries, CML in children is considered an ultra-rare condition. Incidence is unknown but estimations range around 20 new cases per year in Germany (80 million inhabitants) and 100 new cases in the USA. It accounts for less than 3% of all childhood leukemias and less than 10% of all CML cases. Incidence is suspected to be higher in developing countries, with The Max Foundation indicating they have more than 2,000 paediatric CML patients in their database.

Long-term survival of paediatric patients with CML receiving hematopoietic stem cell transplantation from fully-matched related and unrelated donors has been reported between 60-75%, but is associated with significant morbidity. Imatinib and reduced intensity conditioning stem cell transplantation are two promising tools that offer potential for decreasing therapy associated morbidity for patients with CML. Recent publications by study groups indicate that stem cell transplant has been shifted to a 2nd line strategy also in paediatrics.

However, as CML is rare in children and young adults, most data on imatinib therapy is derived from adult studies where average inclusion age is around 45. In addition, there are certain issues like a negative impact on bone growth, uncertainty about long-term effects of TKI therapy, challenges of adherence to therapy, fertility and family planning issues as well as psycho-oncology that are more specific to CML in children and adolescents.

Patient organisations supporting pediatric CML patients and their family members

CML Advocates Network

The CML Advocates Network is both a virtual network and internet platform for patient organisations supporting patients and relatives affected by Chronic Myeloid Leukemia (CML). Launched in 2007, with 4 founding member groups, it has now grown to a network of 131 leukemia patient groups from 96 countries on all continents, offering support by sharing of best practice, information and advice for CML patient representatives.

The CML Advocates Network cooperates very closely with the iCMLf to improve the pediatric CML patient community.

iCMLf Knowledge Centre - Module on Pediatric CML

On the iCMLf Knowledge Centre - an interactive online resource developed by International CML experts from the iCMLf, there is a module on pediatric CML.

Chaired by Professor Meinolf Suttorp and Professor Nirmalya Roy Moulik, this module outlines a comprehensive review of the treatment of pediatric CML. You can acces the presentations here that cover all relevant aspects of pediatric CML:

  1. Difference between adult and pediatric CML (Dr Deepam Pushpam, India)
  2. Predisposition and genetic factors in pediatric CML (Professor Markus Metzler, Germany)
  3. Management of pediatric CML in the resource-restrained setting (Dr Nirmalya Roy Moulik India)
  4. Impact of tyrosine kinase inhibitors on growth and endocrine function in children with CML
    (Professor Meinolf Suttorp, Germany)
  5. Treatment recommendations for pediatric CML - Chronic phase (Professor Frédéric Millot, France)
  6. Treatment recommendations in pediatric CML - Blast phase (Dr Stephanie Sembill, Germany)
  7. Treatment-free remission in pediatric CML (Professor Nobuko Hijiya, USA)
  8. Tyrosine kinase inhibitor toxicity in pediatric CML (Dr Maaike Luesink, The Netherlands)
  9. Parenting in children with CML (Professor Meinolf Suttorp, Germany)

Access additional modules on the iCMLf Knowledge Centre here.

Paediatric CML Case Reviews

This series of paediatric CML case reviews aims to provide a comprehensive discussion of challenging pCML cases from various perspectives to enhance knowledge and improve patient outcomes.

Publications on Pediatric CML

Find the latest papers on Paediatric CML

Guidelines and recommendations

International pediatric panel recommendations
Management of children and adolescents with chronic myeloid leukemia in blast phase
Sembill S et al. Leukemia, 2023;37:505–517
View the full publication

Children's Oncology Group CML Working Group
Management of CML in childen and adolescents
Athale U et al. Pediatr Blood Cancer 2019 Sep;66(9):e27827
View the full publication

See here for more general guidelines on the management of CML

Review articles on pediatric CML

Online case discussions on pediatric CML

Our 'Clinical Case Discussion Forum' features a number of discussions on pediatric CML cases. If you are a physician treating pediatric CML patients, please join our forum and get in touch with other experts.

The latest postings on pediatric CML include:

Ongoing Clinical Trials on Pediatric CML

A number of clinical trials and research activities are currently ongoing to research pediatric CML.
Find more information here.