Historical (Pre–Tyrosine Kinase Inhibitor) Therapy for Childhood CML

Before the tyrosine kinase inhibitor (TKI) era, allogeneic hematopoietic stem cell transplant (HSCT) was the primary treatment for children with chronic myeloid leukemia (CML). Published reports from this period described survival rates of 70% to 80% when an HLA–matched-family donor (MFD) was used in the treatment of children in early chronic phase. Lower survival rates were reported when HLA–matched-unrelated donors were used.[1-3]

Relapse rates were low (less than 20%) when transplant was performed in the chronic phase.[1,2] The primary cause of death was treatment-related mortality, which was increased with HLA–matched-unrelated donors compared with HLA-MFDs in most reports.[1,2] High-resolution DNA matching for HLA alleles appeared to reduce rates of treatment-related mortality, leading to improved outcome for HSCT using unrelated donors.[4]

Compared with transplant in the chronic phase, transplant in the accelerated phase or blast crisis and in the second chronic phase resulted in significantly reduced survival.[1-3] The use of T-lymphocyte depletion to avoid graft-versus-host disease resulted in a higher relapse rate and decreased overall survival,[5] supporting the contribution of a graft-versus-leukemia effect to favorable outcome after allogeneic HSCT.

The introduction of the TKI imatinib as a therapeutic drug targeted at inhibiting the BCR::ABL1 fusion kinase revolutionized the treatment of patients with CML, for both children and adults.[6] Most data on the use of TKIs for CML are from adult clinical trials. For more information, see Chronic Myeloid Leukemia Treatment. The more limited experience in children is described below.