What’s New in t-AML

These publications highlight recent findings in t-AML by researchers around the world:

[The World Health Organization (WHO) uses the term ‘therapy-related myeloid neoplasms’ (t-MN) to cover a spectrum of therapy-related disorders: Acute myeloid leukemia (t-AML); Myelodysplastic syndromes (t-MDS); and Myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN).]

Genetic Abnormalities in t-AML

  • Altered gene expression in hematopoietic cells precedes t-MDS/t-AML development.
    The genetic mechanisms underlying the pathogenesis of t-MDS/t-AML are not well understood.   Li et al. compared the gene expression profiles in hematopoietic stem cells from patients who developed t-MDS/t-AML (n=18) with those that did not (n=37 matched controls) following autologous hematopoietic cell transplantation (aHCT) for Hodgkin lymphoma or non-Hodgkin lymphoma.  Abnormalities were detected in the expression pattern of genes affecting mitochondrial function, hematopoietic regulation, and metabolism in cells several months to years before development of t-MDS/t-AML. Based on these results, a gene expression signature was identified and used to accurately distinguish patients who did or did not subsequently develop the disease.  This study demonstrates that genetic abnormalities associated with t-MDS/t-AML are present before disease onset and can predict patients at risk for this disease.  (Li et al.  Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk. Cancer Cell 20:591-605, 2011.)

t-AML Treatment and Outcomes

  • Allogeneic stem cell transplantation may improve t-MDS/t-AML outcome.
    Kabos et al. investigated the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in 21 pediatric patients for the treatment of t-MDS/t-AML.  Of these patients, 5 proceeded to HSCT without induction chemotherapy, 14 received high-dose cytarabine therapy, and 2 received an anthracycline-based induction therapy.  All patients underwent conditioning regimens selected according to previous therapies.  At a median follow-up of 5.9 years, the 5-year overall survival rate for the entire group of patients was 61.1%, with 12 patients showing no evidence of t-MDS/t-AML.  These results indicate that high-dose cytarabine therapy followed by allogeneic HSCT improves overall disease outcome. (Kobos et al., Allogeneic hematopoietic stem cell transplantation for pediatric patients with treatment-related myelodysplastic syndrome or acute myelogenous leukemia.  Biol Blood Marrow Transplant Nov 10, Epub ahead of print, 2011.)