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Growth deceleration in children treated with imatinib for chronic myeloid leukaemia (Millot F et al. Eur J Cancer, Oct. 2014)

Eur J Cancer. 2014 Oct 24;50(18):3206-3211. doi: 10.1016/j.ejca.2014.10.007. [Epub ahead of print]

Millot F, Guilhot J, Baruchel A, Petit A, Leblanc T, Bertrand Y, Mazingue F, Lutz P, Vérité C, Berthou C, Galambrun C, Sirvent N, Yacouben K,Chastagner P, Gandemer V, Reguerre Y, Couillault G, Khalifeh T, Rialland F.


Abstract

Purpose:

The aim is to study statural growth in a large cohort of children with chronic myeloid leukaemia (CML) treated with front-line imatinib.

Methods:

Retrospective data from 81 children less than 18years of age with CML identified in the French pediatric registry were analysed. Height was expressed as standard deviation score (SDS).

Results:

A gradual decrease in height SDS was observed over time since starting imatinib. The height SDS was significantly lower 12months and 24months after the start of imatinib overall (p<10-4) irrespective of gender and pubertal age. The height SDS was significantly (p<10-4) lower 12months after the start of imatinib in boys and girls, and in the prepubertal age group as well as in the postpubertal age group, respectively. A similar finding was observed in the subgroups of boys and girls starting imatinib at a prepubertal or postpubertal age. Loss in height SDS 12months after the start of imatinib was of the same range in boys when compared to girls and in patients who started imatinib at a prepubertal age compared to those who started at a postpubertal age.

Conclusion:

Growth velocity was altered during the first years of imatinib treatment in boys as well as in girls and in prepubertal age patients as well as in adolescents.

 

Copyright © 2014. Published by Elsevier Ltd.

Differences among young adults, adults and elderly chronic myeloid leukemia patients (Castagnetti F et al. Ann. Oncol, Oct. 2014)

Ann Oncol. 2014 Oct 30. pii: mdu490. [Epub ahead of print]

Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, Abruzzese E, Rossi G, Iurlo A, Martino B, Pregno P, Stagno F, Cuneo A, Bonifacio M,Gobbi M, Russo D, Gozzini A, Tiribelli M, de Vivo A, Alimena G, Cavo M, Martinelli G, Pane F, Saglio G, Rosti G; on behalf of the GIMEMA CML Working Party.

 

Abstract

Background:

The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage.

Patients and methods:

To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analysed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period.

Results:

Young adults (18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, p<0.001), and the greater spleen size (median value: 4.5 cm, 3.0 cm and 1.0 cm, p<0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among young adults, than among adult and elderly patients (18%, 9%, and 6%, p<0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in young adults, and the probability of transformation was higher (16%, 5% and 7%, p=0.011).

Conclusions:

The characteristics of CML or the host response to leukemia, differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome.

 

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

 

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.

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.
Full text download of the article here

 

 

 

 

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. 

 

 

  1. Sustained complete molecular remission after imatinib discontinuation in children with chronic myeloid leukemia (Moser et al. Pediatr Blood Cancer, May 2014)
  2. Bone metabolism, growth rate and pubertal development in children with chronic myeloid leukemia treated with imatinib during puberty (Giona et al. Haematologica, Sept. 2012)
  3. How I treat: childhood CML (Andolina et al. Blood, Dec. 2011)
  4. Imatinib Has Adverse Effect on Growth in Children With Chronic Myeloid Leukemia (Bansal et al. Pediatr Blood Cancer, Nov. 2011)