CML is a very rare disease in children and adolescents accounting for less than 5% of all CML cases. Only scant data is available regarding epidemiology, presenting features and outcome of CML in this age range.
An international registry (I-CML-Ped Study) was established to assess epidemiology, management and outcome of CML in the pediatric population. The main objectives of the study are the following: i) to describe the clinical and biological characteristics of CML in a large cohort of patients less than 18 years of age, ii) to identify prognostic factors in this age-group in order to optimize individual treatment choices iii) to determine side effects and long term effects of treatments, mainly the tyrosine kinase inhibitor effect, on growth and development of a pediatric cohort.
All national pediatric study groups were invited to participate. All newly diagnosed children and adolescents less than 18 years diagnosed later than January 2000 has to be notified and collection of the follow- up data is planned. The study is strictly observational and informed consent from the patient and/or the legal guardians is required for enrollment. The study was started in January 2011.
As of July 2012, 200 patients (pts) from 9 countries have been registered. There was a male preponderance (59%). The median age at diagnosis was 11.6 years (range, 8 months −18 years); 8% of the patients were younger than 4 years. Clinical and biological data at initial diagnosis so far is available in 150 pts. At time of diagnosis 92% were in chronic phase, 6% in accelerated phase and 2% in blastic phase according to the European Leukemia Net criteria. The Sokal risk group distribution was: 13% low, 33% intermediate and 55% high risk. The majority of the patients showed a Lansky score of 100 (67%) or 90 (16%). Splenomegaly was present in 76% of patients. The median of the spleen size below the costal margin was 8 cm (range: 0 to 25 cm). The median of the leukocyte count was 250×109/L (range: 5 to 1037). Additional chromosomal abnormalities in Ph-positive cells were observed in 2.3 % of the patients. The BCR-ABL transcript type was available in 100 patients: b3a2 51%, b2a2 40%, b3a2 plus b2a2 7% and b2a3 2%. The median follow-up time is 28 months (range, 2–138). Five deaths were recorded. The estimated overall survival rate at 42 months is 97% (CI 95%, 91–99). Forty seven (63%) of 75 assessable patients for cytogenetic response achieved complete cytogenetic response 12 months after the start of the treatment (imatinib: 43 pts, switch to dasatinib after imatinib failure: 3 pts, interferon + cytosine arabinoside: 1pt). Data collection regarding molecular assessment is ongoing and will be presented.
This is the largest study reporting on children and adolescents with CML. The data indicates that children and adolescents with CML presented with clinical and biological differences compared to adult patients with CML. Whether these differences translate into a different outcome still remains to be determined.
The I-CML Ped study is supported by an unrestricted grant from Novartis Pharmaceutical Company
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.