Changes to This Summary (04/09/2015)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added Corrigan et al. as reference 2.
Revised text to state that the prevalence of FLT3-ITD is increased in certain genomic subtypes of pediatric AML patients, including those with the NUP98-NSD1 fusion gene, of which 80% to 90% have FLT3-ITD. Also added text to state that approximately 15% of patients with FLT3-ITD have NUP98-NSD1, and patients with both FLT3-ITD and NUP98-NDS1 have a poorer prognosis than do patients with FLT3-ITD and without NUP98-NDS1 (cited Ostronoff et al. as reference 81).
Added Tarlock et al. as reference 105.
Added text about the frequency of NUP98-NSD1 in the pediatric population and that the presence of both NUP98-NSD1 and FLT3-ITD independently predicted for poor prognosis.
The Classification of Myelodysplastic Syndromes in Children subsection was extensively revised.
Added text to state that the subclonal presence of SETBP1 mutations have been reported to be associated with an 18% ± 9% 5-year event-free survival (EFS), compared with a 51% ± 8% EFS for those without such mutations (cited Stieglitz et al. as reference 204).
Added Zhang et al. as reference 54.
Revised text to state that the impact of arsenic induction on EFS and overall survival (OS) has not been well characterized in children, although early results appear promising (cited Cheng et al. as reference 54 and level of evidence 3iiA).
Revised text to state that other genes shown to be mutated in MDS include EZH2, DNMT3A, ASXL1, IDH1/2, RUNX1, ETV6-TEL, GATA2, DKC1, LIG4, and TP53 (cited Zhang et al. as reference 4).
Added text about germline mutations and inherited conditions that are associated with a significantly increased risk of MDS (cited Ludwig et al., Wechsler et al., Ghauri et al., Auer et al., and Vinh et al. as references 11, 14, 17, 18, and 19, respectively).
Revised text to state that some of the agents that have shown antileukemia activity against JMML include etoposide, cytarabine, thiopurines, isotretinoin, and farnesyl inhibitors, but none of these have been shown to improve outcome (cited Stieglitz et al. as reference 27 and level of evidence 2B).
Added text to state that early molecular responses, such as polymerase chain reaction–based minimal residual disease measurement at 3 months of therapy showing less than or equal to 10% BCR-ABL1/ABL, have been reported to be associated with improved progression-free survival, similar to early molecular response data in adults (cited Millot et al. as reference 31).
Added text to state that the question remains about whether a pediatric patient with CML should receive an allogeneic transplant when multiple tyrosine kinase inhibitors (TKIs) are available. The potential advantages and disadvantages need to be discussed with the patient and family. While hematopoietic stem cell transplantation is currently the only known definitive curative therapy for CML, patients discontinuing treatment with TKIs after sustained molecular remissions and remaining in molecular remission have been reported (cited Ross et al. as reference 45).
Added text to state that the diagnosis of recurrent or relapsed AML according to Children's Oncology Group (COG) criteria is essentially the same as the criteria for making the diagnosis of AML. Usually this is defined as patients having more than 5% bone marrow blasts and a diagnosis of AML according to World Health Organization classification criteria (cited Arber et al. as reference 1).
Added text to state that specific molecular alterations at the time of relapse have been reported to impact subsequent survival. For instance, the presence of either WT1 or FLT3-ITD mutations at first relapse were associated as independent risk factors for worse OS in patients achieving a second remission (cited Bachas et al. as reference 7).
Added text about the COG AAML0523 trial that evaluated the combination of clofarabine plus high-dose cytarabine in patients with relapsed AML (cited Cooper et al. as reference 16 and level of evidence 2Di). Also added text to state that in a COG phase II study, the addition of bortezomib to idarubicin and low-dose cytarabine resulted in an overall complete remission (CR) rate of 57%, and the addition of bortezomib to etoposide and high-dose cytarabine resulted in an overall CR rate of 48% (cited Horton et al. as reference 17).
Added text to state that gemtuzumab ozogamicin is currently not available in the United States, except for compassionate-use approval.
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.