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Managing children with CML: Pediatric CML Guideline if IBFM (Fuente et al. Br J Haematology, July 2014)

Recommendations for the management of CML in children and young people up to the age of 18 years

British Journal of Haematology, doi:10.1111/bjh.12977

Chronic myeloid leukaemia in children and young people is a relatively rare form of leukaemia that shows increased incidence with age and some evidence suggests that the molecular basis differs from that in adults. Significant advances in targeted therapy with the development and use in children of tyrosine kinase inhibitors and the ability to monitor and understand the prognostic significance of minimal residual disease by standardized molecular techniques has shifted the management of this condition from bone marrow transplantation as the main therapeutic modality to individualized treatment for each patient based on achieving specific milestones. The physiological changes occurring during childhood, particularly those affecting growth and development and the long-term use of treatment, pose specific challenges in this age group, which we are only beginning to understand.
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Imatinib cessation in children and adolescents with chronic myeloid leukemia in chronic phase (Millot et al. Pediatr Blood Cancer, Feb. 2014)

Pediatr Blood Cancer. 2014 Feb;61(2):355-7. doi: 10.1002/pbc.24521. Epub 2013 Sep 17.

 

Millot F, Claviez A, Leverger G, Corbaciglu S, Groll AH, Suttorp M.

 

 

Abstract

 
Imatinib can be safely discontinued in adults with chronic myeloid leukemia (CML) where there is a prolonged complete molecular response (CMR). No data are available in the pediatric population. Six children with CML discontinued imatinib by themselves. Only three of them were in CMR but for <2 years. A significant increase in transcript level was observed in all six patients after cessation of imatinib and five patients lost the major molecular response (MMR). Four patients regained the MMR within 3 months. Cessation of imatinib in children is not recommended outside a trial, particularly in patients without prolonged CMR.
© 2013 Wiley Periodicals, Inc.

Sustained complete molecular remission after imatinib discontinuation in children with chronic myeloid leukemia (Moser et al. Pediatr Blood Cancer, May 2014)

Pediatr Blood Cancer. 2014 May 9. doi: 10.1002/pbc.25090. [Epub ahead of print]

Moser O, Krumbholz M, Thiede C, Tauer JT, Janz I, Lauten M, Dilloo D, Metzler M, Suttorp M.

 

Abstract

Approximately 40% of adults with chronic myeloid leukemia (CML) in prolonged complete molecular response (CMR) remain in CMR after imatinib discontinuation. Corresponding information in children is lacking. Two children with CML in CMR for 48 and 19 months after imatinib discontinuation showed low-level fluctuating disease at RNA transcript and genomic DNA levels. Both patients were low risk according to adult criteria. Since adults with molecular relapse responded to re-introduction of imatinib, we postulated that treatment discontinuation in low risk children might be justified within clinical trials with close monitoring. This may help to minimize exposure to imatinib and its potential side effects. Pediatr Blood Cancer
 
© 2014Wiley Periodicals, Inc.

Blood and Marrow Transplant Clinical Trials Network: progress since the State of the Science Symposium 2007 (Ferrara JL. Biol Blood Marrow Transplant, Feb. 2014)

Biol Blood Marrow Transplant. 2014 Feb;20(2):149-53. doi: 10.1016/j.bbmt.2013.11.006. Epub 2013 Nov 12.

Ferrara JL

 

 

 

Abstract

Outcomes of hematopoietic cell transplantation continue to improve. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from related and unrelated donors. In June 2007, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) convened a State of the Science Symposium (SOSS) in Ann Arbor and identified 11 high priority clinical trials for the network to pursue. This article reviews both the status of those trials and the record of achievement of the BMT CTN as it convenes another SOSS in Grapevine, Texas in February 2014.
 
Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. 

 

 

Bone metabolism, growth rate and pubertal development in children with chronic myeloid leukemia treated with imatinib during puberty (Giona et al. Haematologica, Sept. 2012)

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

 

Fiorina Giona, Stefania Mariani, Lucio Gnessi, Maria Luisa Moleti, Massimiliano Rea, Annalisa De Vellis, Deborah Marzella, Anna Maria Testi, and Robin Foa'

Haematologica 2012, DOI: 10.3324/haematol.2012.067447 4

 

...An altered bone and mineral metabolism, a reduction of testosterone and gynecomastia referred to PDGF-R and c-KIT inhibition in normal cells have been reported in adults treated with IM.2-4 So far, most of the data on the long-term side-effects of IM in children who have received IM concerns its impact on growth.5-7. We hereby report 4 CML pre-pubertal patients (3 males and 1 female; median age at the beginning of the IM, 10.6 years) in complete cytogenetic response (CCyR) with IM who were regularly monitored, between May 2004 and June 2011, to evaluate the bone and mineral metabolism, as well as growth and pubertal development. [...] In conclusion, the side effects observed in our patients (deceleration of longitudinal growth, reduction of BMD and fertility) raise some concerns that children long-exposed to IM prior to puberty may behave differently from adults. Since the number of children on treatment with TKIs is constantly increasing, DEXA, CTX, growth velocity in all patients, and FSH and inhibin-B in all males should be regularly monitored to plan the optimal treatment strategy in this category of patients.

  1. How I treat: childhood CML (Andolina et al. Blood, Dec. 2011)
  2. Imatinib Has Adverse Effect on Growth in Children With Chronic Myeloid Leukemia (Bansal et al. Pediatr Blood Cancer, Nov. 2011)
  3. Imatinib Is Effective in Children With Previously Untreated CML in Early Chronic Phase: Results of the French National Phase IV Trial (Millot et al. J Clin Oncology, June 2011)
  4. CML in Children: Diagnostics and Management (Suttorp, Tauer, Millot, Publ. at 3rd Midsommer Meeting on Pediatric Hematology, June 2011)