Treatment of Pediatric Chronic Myeloid Leukemia in the Year 2010: Use of Tyrosine Kinase Inhibitors and Stem-Cell Transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the only proven cure for chronic myeloid leukemia (CML), a rare malignancy in childhood. With the excellent results induced by the tyrosine kinase inhibitor (TKI) imatinib in adults in the last decade, the appropriate management of children with CML has also changed radically, and only a minority are now transplanted as a front-line treatment. Data on pediatric experiences with imatinib in CML from controlled trials remain very limited, but this review of available data describes the role of imatinib in children with CML, addressing: 1) the starting dose; 2) pharmacokinetics in childhood; 3) possible adverse effects, with a focus on the still-growing skeleton; 4) early monitoring of treatment efficacy in an attempt to avoid failure; 5) the timing of allo-SCT in children; and 6) treatment of CML relapse after allo-SCT. Because the characteristics of CML in children seem to overlap extensively with what is described in adult internal medicine, most answers and pediatric algorithms are adapted from the treatment of CML in adults. Today in 2010, allo-SCT in children should be postponed until CML becomes refractory to imatinib. The approach for young patients with suboptimal responses is unclear because data on the efficacy and safety of second-generation TKIs in childhood are almost entirely missing. Other than being included in a formal trial on second-generation TKIs, allo-SCT for patients failing imatinib remains the first choice.

Analysis of outcomes in adolescents and young adults with chronic myelogenous leukemia treated with upfront tyrosine kinase inhibitor therapy

“…48 Several studies have highlighted the outcomes in ALL and, more recently, AML. 49 However, to our knowledge, this is the first report to address CML in AYA. This group represents only 13% of all CML patients treated with TKI at our institution during the study period.…”

Induction of spermatogenesis after stem cell therapy of azoospermic guinea pigs

“…The second point is the pharmacological character of busulfan. Busulfan is a chemotherapeutic agent that is mostly used in low doses and for a long time in the treatment of chronic myeloid leukemia (SUTTORP and MILLOT, 2010), and before any allogeneic transplantation of hematopoietic cells, it is administered as a myeloablastive agent (BARTELINK et al, 2014). The last point is related to the BM-MSCs character, which is shown to be not only hypo-immunogenic but also to have immune-surveillance or immunosuppressive properties upon transplantation, and to be a good candidate for allogeneic transplantation (AI et al, 2012).…”

How I treat childhood CML

“…61 There remains significant controversy regarding cardiac toxicity with imatinib, and many authors conclude that there may be no increased risk of heart dysfunction. 40,48 To date, no reports of cardiac dysfunction in children have surfaced. Although it is unknown whether long-term administration of TKI affects heart function, one group observed left ventricular abnormalities in mice treated with imatinib because of c-ABL inhibition.…”

“…One group estimated that the efficacy of imatinib has been evaluated in less than 200 children to date (as of 2010). 48 The landmark phase 1 trial from the Children's Oncology Group evaluated 31 children with leukemia who received imatinib at doses ranging from 260 to 570 mg/m 2 . 49 Imatinib was extremely well tolerated, and a maximum tolerated dosage could not be identified.…”