Bone metabolism, growth rate and pubertal development in children with chronic myeloid leukemia treated with imatinib during puberty

1,736

2,099

Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward define optimal response, whereas >10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome–positive [Ph+] >95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.

Section: Side Effectsmentioning

confidence: 99%

European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013

Baccarani

Deininger

Rosti

et al. 2013

1,736

2,099

“…45,46 In children, various groups have reported substantial growth abnormalities associated with imatinib in children with CML. [47][48][49][50][51][52][53][54][55] There is less experience with second-and third-generation TKIs in children, but dasatinib also seems to have a similar effect on growth. 48 It appears that prepubertal children are affected more significantly, 29 and though they may experience "catch-up" growth in puberty, their final height is lower than the predicted midparental height.…”

mentioning

confidence: 99%

Pediatric chronic myeloid leukemia is a unique disease that requires a different approach

Hijiya

Schultz

Metzler

et al. 2016

164

176

Chronic myelogenous leukemia (CML) in children is relatively rare. Because of a lack of robust clinical study evidence, management of CML in children is not standardized and often follows guidelines developed for adults. Children and young adults tend to have a more aggressive clinical presentation than older adults, and prognostic scores for adult CML do not apply to children. CML in children has been considered to have the same biology as in adults, but recent data indicate that some genetic differences exist in pediatric and adult CML. Because children with CML may receive tyrosine kinase inhibitor (TKI) therapy for many decades, and are exposed to TKIs during a period of active growth, morbidities in children with CML may be distinct from those in adults and require careful monitoring. Aggressive strategies, such as eradication of CML stem cells with limited duration and intensive regimens of chemotherapy and TKIs, may be more advantageous in children as a way to avoid lifelong exposure to TKIs and their associated adverse effects. Blood and marrow transplantation in pediatric CML is currently indicated only for recurrent progressive disease, and the acute and long-term toxicities of this option should be carefully evaluated against the complications associated with lifelong use of TKIs.

“…Several groups report imatinib-induced growth delay, especially in prepubertal children, due to altered bone metabolism and growth hormone suppression. [54][55][56] The International BFM Study Group and other experts recommended that guidelines for children with CML should follow those for adults. 57,58 However, there are still concerns for lifelong safety and quality of life when using TKIs in pediatric CML.…”

Section: Treatment Of Children With CMLmentioning

confidence: 99%

The role of stem cell transplantation for chronic myelogenous leukemia in the 21st century

Barrett

Ito

2015

The introduction of tyrosine kinase inhibitors (TKIs), a treatment of chronic myelogenous leukemia (CML), has largely replaced curative strategies based on allogeneic stem cell transplantation (SCT). Nevertheless, SCT still remains an option for accelerated/blastic-phase and selected chronic-phase CML. Transplant outcomes can be optimized by peritransplant TKIs, conditioning regimen, BCR-ABL monitoring, and relapse management. Controversies exist in transplant timing, pediatric CML, alternative donors, and economics. SCT continues to serve as a platform of “operational cure” for CML with TKIs and immunotherapies.