Front-line imatinib treatment in children and adolescents with chronic myeloid leukemia: results from a phase III trial

Abstract

A total of 156 patients (age range 1.3-18.0 years, median 13.2 years; 91 (58.3%) male) with newly diagnosed CML (N = 146 chronic phase (CML-CP), N = 3 accelerated phase (CML-AP), N = 7 blastic phase (CML-BP)) received imatinib up-front (300, 400, 500 mg/m, respectively) within a prospective phase III trial. Therapy response, progression-free survival, causes of treatment failure, and side effects were analyzed in 148 children and adolescents with complete data. Event-free survival rate by 18 months for patients in CML-CP (median follow-up time 25 months, range: 1-120) was 97% (95% CI, 94.2-99.9%). According to the 2006 ELN-criteria complete hematologic response by month 3, complete cytogenetic response (CCyR) by month 12, and major molecular response (MMR) by month 18 were achieved in 98, 63, and 59% of the patients, respectively. By month 36, 86% of the patients achieved CCyR and 74% achieved MMR. Thirty-eight patients (27%) experienced imatinib failure because of unsatisfactory response or intolerance (N = 9). In all, 28/148 patients (19%) underwent stem cell transplantation (SCT). In the SCT sub-cohort 2/23 patients diagnosed in CML-CP, 0/1 in CML-AP, and 2/4 in CML-BP, respectively, died of relapse (N = 3) or SCT-related complications (N = 2). This large pediatric trial extends and confirms data from smaller series that first-line imatinib in children is highly effective.

IKZF1 deletion and co‐occurrence with other aberrations in a child with chronic myeloid leukemia progressing to acute lymphoblastic leukemia

“…Just a few studies have reported CML in very young patients. The rarity of CML in this age group hinders the establishment of specific risk criteria and protocols for handling the disease in pediatric patients . Despite a low Sokal score, our patient rapidly progressed to blast crisis.…”

Bleeding signs due to acquired von Willebrand syndrome at diagnosis of chronic myeloid leukaemia in children

“…The haematological findings of the total cohort are reported in Table . More details on CML and patients’ status at diagnosis, treatment applied and overall outcome have been reported elsewhere (Suttorp et al , ).…”

“…Several prognostic CML scoring systems in adults (e.g. Sokal, Hasford or EURO scores) consider thrombocytosis as an adverse risk factor (Pfirrmann et al , ) and thus the observation of a higher proportion of children with thrombocytosis matches well with other characteristics of CML, pointing to a more aggressive presentation of the disease when diagnosed in the first decades of life (Pemmaraju et al , ; Kalmanti et al , ; Gurrea Salas et al , ; Hijiya et al , ; Millot et al , ; Suttorp et al , ).…”

Management of chronic myeloid leukemia in children and adolescents: Recommendations from the Children's Oncology Group CML Working Group

“…On the other hand, the need for life‐long therapy with TKI and the known and unknown late effects of TKI may make SCT an attractive option for some. Therefore, there remains controversy regarding the role of SCT in pediatric patients with CML‐CP responsive to their first TKI therapy …”

“…Although SCT can be curative, there remains the risk of substantial transplant‐related morbidity and mortality, including infertility and long‐term complications, and the risk of later relapse . With recent advances surrounding SCT, children undergoing transplant have fewer complications and better outcomes compared to those of adults and hence SCT may be an option for patients who cannot or do not want to continue lifelong TKI therapy …”