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Increased megakaryocytic proliferation, pro-platelet deposition and expression of fibrosis-associated factors in children with chronic myeloid leukemia with bone marrow fibrosis (Hussein K et al. Leukemia, February 2017)

Leukemia, February 2017
Hussein K et al.  


Abstract

Pediatric chronic myeloid leukemia (ped-CML) is rare and ped-CML with fibre accumulation in the bone marrow (MF) is thought to be even rarer. In adults (ad-CML), fibrosis represents an adverse prognostic factor. So far, the pro-fibrotic changes in the bone marrow microenvironment have not been investigated in detail in ped-CML. From a total of 66 ped-CML in chronic phase, biopsies were analysable and 10 had MF1/2 (MF1, n=8/10; MF2, n=2/10). We randomly selected 16 ped-CML and 16 ad-CML cases with and without fibrosis (each n=8) as well as 18 non-neoplastic controls. Bone marrow samples were analysed with a real-time PCR-based assay (including 127 genes for pediatric cases) and by immunohistochemistry. We found increased expression of megakaryocytic genes in ped-CML. The number of megakaryocytes and pro-platelets are increased in CML patients but the most significant increase was noted for ped-CML-MF1/2. Anti-fibrotic MMP9 expression was lower in children than in adults. Cell mobilisation-related CXCL12 was decreased in young and adult patients with CML but not the corresponding receptor CXCR4. In summary, fibre accumulation in ped-CML-MF1/2 is associated with increased megakaryocytic proliferation and increased interstitial pro-platelet deposition. Deregulated expression of matrix modulating factors shifts the bone marrow microenvironment towards fibrosis.

 

 

 

 

Optimal management for pediatric chronic myeloid leukemia (Tanzizawe A. Pediatrics International, March 2016)

Pediatrics International, March 2016 
Akihiko Tanzizawa

Response dynamics of pediatric patients with chronic myeloid leukemia on imatinib therapy (Proschmann R et al. Haematologica, November 2016)

Haematologica, November 2016
Proschmann R. et al

 

Link to full paper 

Early response does not predict outcome in children and adolescents with chronic myeloid leukemia treated with high-dose imatinib (Giona F et al. Br J Haematol, Dec 2016)

Br J Haematol, December 2016
Giona F. et al

 

Link to full paper 

Survival trends in childhood chronic myeloid leukaemia in Southern-Eastern Europe and the United States of America (Karalexi MA et al. Eur J Cancer, Sept 2016)

Eur J Cancer 
Karalexi MA et al.  


Abstract

Aim: 

To assess trends in survival and geographic disparities among children (0-14 years) with chronic myeloid leukaemia (CML) before and after the introduction of molecular therapy, namely tyrosine kinase inhibitors (TKIs) in Southern-Eastern European (SEE) countries and the USA.

Methods: 

We calculated survival among children with CML, acute lymphoblastic (ALL) and acute myeloid leukaemia (AML) in 14 SEE (1990-2014) cancer registries and the U.S. Surveillance, Epidemiology and End Results Program (SEER, 1990-2012). We used Kaplan-Meier curves and multivariate Cox regression models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: 

Among 369 CML cases, substantial improvements were noted in 2-year survival during the post-TKI (range: 81-89%) compared to pre-TKI period (49-66%; HR: 0.37, 95% CI: 0.23-0.60). Risk of death was three times higher for <5-year-old children versus those aged 10-14 years (HR: 3.03, 95% CI: 1.85-4.94) and 56% higher for those living in SEE versus SEER (HR: 1.56, 95% CI: 1.01-2.42). Regardless of geographic area and period of TKI administration, however, age seems to be a significant determinant of CML prognosis (pre-TKI period, HR0-4y: 2.71, 95% CI: 1.53-4.79; post-TKI period, HR0-4y: 3.38, 95% CI: 1.29-8.85). Noticeably, post-TKI survival in CML overall approximates that for ALL, whereas therapeutic advancements for AML remain modest.

Conclusion: 

Registry data show that introduction of molecular therapies coincides with revolutionised therapeutic outcomes in childhood CML entailing dramatically improved survival which is now similar to that in ALL. Given that age disparities in survival remain substantial, offering optimal therapy to entire populations is an urgent priority.


Copyright © 2016 Elsevier Ltd. All rights reserved.

 

 

  1. Impact of age on the survival of pediatric leukemia: an analysis of 15083 children in the SEER database (Wang Y et al. Oncotarget, Aug 2016)
  2. Pediatric chronic myeloid leukemia with inv(3) (q21q26.2) and T lymphoblastic transformation: a case report (Lewen M et al. Biomark Res, July 2016)
  3. Very long survival in complete cytogenetic remission in an adolescent with lymphoid blast crisis of chronic myeloid leukemia after treatment with intensive ALL-direct chemotherapy combined with continous imatinib (Maschan A et al. Pediatr Blood Cancer, Ju
  4. Outcomes following bone marrow transplantation in children with accelerated phase or blast crisis chronic myelogenous leukemia in the era of tyrosine kinase inhibitors (Shulman DS et al. J Pediatr Hematol, July 2016)