Chronic Myeloid Leukemia

Proposal

Current recommendations of chronic myeloid leukemia (CML) management have been evolutionary changed over time. So far, several tyrosine kinase inhibitors (TKIs) such as imatinib, dasatinib, nilotinib, and bosutinib have been developed, and now imatinib and nilotinib are both the first-line treatment modality of early CML. These TKIs have demonstrated durable efficacy and leukemia-free survival in early chronic phase CML. Most of Abl mutations frequently detected in imatinib resistant-patients have been well controlled by novel tyrosine kinase inhibitors (NTKIs) such as dasatinib, nilotinib, and bosutinib.

However some patients show suboptimal response and treatment failure with TKI treatment and different strategies such as sequential/combinational therapy with different NTKIs, new tyrosine kinase inhibitors, systemic chemotherapy, and/or allografting should be selectively applied in these cases.

According to ELN 2009 recommendation, standard frontline treatment in early CP-CML was confirmed as imatinib 400 mg daily. Imatinib should be continued indefinitely in optimal responders. Suboptimal responders may continue on imatinb, at the same or higher dose, or may be eligible for investigational therapy with second-generation TKIs. In instances of imatinib failure, second-generation TKIs are recommended, followed by allogeneic hematopoietic stem-cell transplantation only in instances of failure and, sometimes, suboptimal response, depending on transplantation risk.

The outcome of allogeneic SCT is influenced by several host-, disease-, and treatment-associated factors. The assessment of the long-term outcome of alloHSCT from HLA identical siblings is still based on the data collected by the International and the European Registries between 1978 and 1997. These results encompassed a period of 15 to 20 years that had survival rates of 50% and 34%, respectively. As the dilemmas surrounding the choice of allogeneic SCT are not completely resolved in the era of various TKIs, the treatment algorithm will continue to evolve as data mature to the risks and benefits.

To decide optimal time of transplantation, a careful monitoring the response to Imatinib and precise assessment of Imatinib failure are both crucial processes for this alternative approach. Therefore we will conduct several retrospective and prospective analysis to explore relationship between TKI use and transplant outcome using data-set of APBMT

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Chairman: Dong-Wook Kim (Korea)

dwkim@catholic.ac.kr

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