Lymphoblastic predominance of blastic phase in children with chronic myeloid leukaemia treated with imatinib: A report from the I-CML-Ped Study

• Published in: European journal of cancer (1990) 2020-09, Vol.137, p.224-234
• Main Authors: Meyran, Deborah, Petit, Arnaud, Guilhot, Joelle, Suttorp, Meinolf, Sedlacek, Petr, De Bont, Eveline, Li, Chi Kong, Kalwak, Krzysztof, Lausen, Birgitte, Culic, Srdjana, de Moerloose, Barbara, Biondi, Andrea, Millot, Frédéric
• Format: Article
• Language: English
• Subjects: Accelerated phase; Adolescent; Blast Crisis - pathology; Blastic phase; Child; Child, Preschool; Children; Chronic myeloid leukaemia; Chronic myeloid leukemia; Confidence intervals; Enzyme inhibitors; Evolution; Female; Haematopoietic stem cell transplantation; Hematopoietic stem cells; Humans; Imatinib; Imatinib Mesylate - therapeutic use; Infant; Inhibitor drugs; Kinases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Life Sciences; Lymphocytes - metabolism; Male; Medical prognosis; Pediatrics; Protein-tyrosine kinase; Rare diseases; Statistical analysis; Stem cell transplantation; Stem cells; Survival; Targeted cancer therapy; Transplantation; Transplants & implants; Tyrosine; Tyrosine kinase inhibitors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2020.06.024

Chronic myeloid leukaemia (CML) is a rare disease in children. The frequency and outcome of children evolving to accelerated phase (AP) or blastic phase (BP) under treatment with imatinib is unknown. The aim of the current study is to assess the incidence of progression from CML in chronic phase with imatinib frontline in a paediatric setting and describe the management and outcome of these patients. In the I-CML-Ped Study database (www.clinicaltrials.gov, #NCT01281735), 19 of 339 paediatric patients in chronic phase treated with imatinib in the frontline evolved to CML-AP or CML-BP. With a median follow-up of 38 months (range: 2–190 months), the cumulative incidence of progression at 1 and 3 years was 3% (confidence interval [CI] 95%: 1–5%) and 7% (CI 95%: 4–11%), respectively. We observed a large predominance of lymphoid-BP (70%) over myeloid-BP (30%) with imatinib in frontline therapy. Sixteen patients underwent haematopoietic stem cell transplantation, and eight were treated with a tyrosine kinase inhibitor after transplant. Only the transplanted patients are alive. The 5-year overall survival rate of children with CML-AP/BP is 44%, with no statistical difference between the lymphoid-BP and myeloid-BP outcome. Children evolving to AP or BP under treatment with imatinib have a very poor prognosis with an overall survival under 50%, much worse than children with advanced phase at diagnosis. •Progression of chronic myeloid leukaemia in children under imatinib treatment.•Incidence of progression at 1 and 3 years is 3% and 7%, respectively.•Lymphoid phenotype predominance in blastic phase with upfront imatinib treatment.•Poor outcome when transformation occurs while on tyrosine kinase inhibitor therapy.