The Experience of the International Registry for Chronic Myeloid Leukemia (CML) in Children and Adolescents (I-CML-Ped Study): Pronostic Consideration

Aims: An international registry (I-CML-Ped Study)was established to assess epidemiology, management and outcome of CML in the pediatric population.

Methods: All national pediatric study groups were invited to include newly diagnosed children and adolescents less than 18 years with CML diagnosed later than January 2000.

Results: Since January 2011, 351 patients from 12 countries have been registered. Clinical and biological data at initial diagnosis are available in 278 patients.There was a male preponderance (57%). The median age at diagnosis was 12.4 years (range, 9 months -17.5 years); 6% of the patients were younger than 4 years. At time of diagnosis 92% of the children were in chronic phase, 8% in accelerated phase and 1% in blastic phase according to the European Leukemia Net criteria. The Sokal risk group distribution was: 18% low, 31% intermediate and 51% high risk. The majority of the patients showed a Lansky score of 100 (59%) or 90 (21%). Splenomegaly was present in 76% of patients. The median of the spleen size below the costal margin was 11 cm (range: 1 to 25 cm). The median of the leukocyte count was 235x10⁹/L (range: 5 to 1038). Additional chromosomal abnormalities in Ph-positive cells were observed in 6 % of the patients. The BCR-ABL transcript type was available in 227 patients: b3a2 54%, b2a2 38%, b3a2-b2a2 6% and b2a3 2%. The median follow-up time is 39 months (range, 0.5-161). Eight deaths were recorded. The estimated overall survival rate at 60 months is 95% (95%CI 89-97). Irrespective of treatment and follow-up, 124 (73%) of 169 assessable patients for cytogenetic response achieved complete cytogenetic response (CCyR). Exploratory analyses were performed in newly diagnosed patients regarding clinical and biological factors influencing the achievement of CCyR 12 months after starting imatinib. In univariate analyses, the Eutos score, the spleen size, the hematocrit level, the lymphocyte count and immature cells in peripheral blood, the percentage of granulocytes and monocytes in the marrow were identified as potential prognostic factors. However, only the percentage of the granulocytes in the marrow was identified as independent factor of achievement of CCyR at 12 months in multivariate analysis. Data collection and quality control regarding molecular assessment are ongoing.

Conclusion: The data indicates that children and adolescents with CML presented with clinical and biological differences compared to adult patients with CML. Identification of prognostic factors is needed to optimize the strategy in the pediatric population.

Acknowledgment: The I-CML Ped study is supported by an unrestricted grant from Novartis Pharmaceutical Company