[Objective] Previous studies showed that c-KIT mutation and <3log reduction of minimal residual disease (MRD) were two poor prognostic markers for acute myeloid leukemia (AML) with t(8;21) . However, How to deal with c-KIT- mutated t(8;21)AML patients with >3log reduction of MRD remains undefined. To answer this question, we performed this study.

[Methods] The current retrospective study consisted of 70 newly diagnosed patients with c-KIT- mutated t(8;21)AML during July 2005 and March 2016 in Peking University People's Hospital. Induction treatment included standard 3+7' regimen or HAA regimen. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was recommended to all patients with an available donor after 2-3 cycles of consolidation treatment with high-dose cytarabine(HDAC). Patients without a donor or refusing HSCT received HDAC-based intensive treatment. MRD was determined by RUNX1/RUNX1T1 transcript levels detected by Q-PCR. The last follow-up time was July 2016.

[Results] Sixty-nine out of 70 patients achieved complete remission(CR).Two patients relapsed after first cycle of consolidation treatment. There were 60 patients having the results of MRD after 2 cycles of consolidation treatment (Figure 1). Thirty-four patients achieved >3log reduction of RUNX1/RUNX1T1 transcript levels (defined as major molecular remission, MMR). There were 16 and 18 patients finally receiving chemotherapy and allo-HSCT. Twenty-six patients did not achieve MMR, and 12 and 14 patients finally receiving chemotherapy and allo-HSCH, respectively. For patients achieving MMR, the 4-year cumulative incidence of relapse (CIR) and disease-free survival (DFS) were 84.8% vs.6.7% (p<0.001) and 20.6% vs.87.5% (p<0.001) when receiving chemotherapy or allo-HSCT(Figure 2). For patients not achieving MMR, the 4-year CIR and DFS were 100% vs.30.8% (p<0.001) and 0% vs.60% (p<0.001) when receiving chemotherapy or allo-HSCT (Figure 2). Multivariate analysis revealed that MRD status (MMR or non-MMR and treatment choice (HSCT or chemotherapy) were independent prognostic factors for relapse, DFS.

[Conclusion] We concluded that c-KIT- mutated t(8;21)AML patients with >3log reduction of MRD conferred a very high relapse and need allo-HSCT to improve outcome.

Figure 1
Figure 1. The flowchart of the study.
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The flowchart of the study.

Figure 1
Figure 1. The flowchart of the study.
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The flowchart of the study.

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Figure 2
Figure 2. Thecumulative incidence of relapse (CIR) and disease-free survival (DFS) of c-KIT mutated t(8;21)AML patients. .. / Note : MMR: major molecular remission; CT: chemotherapy. HSCT: hematopoietic stem cell transplantation.
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Thecumulative incidence of relapse (CIR) and disease-free survival (DFS) of c-KIT mutated t(8;21)AML patients. ..

Note : MMR: major molecular remission; CT: chemotherapy. HSCT: hematopoietic stem cell transplantation.

Figure 2
Figure 2. Thecumulative incidence of relapse (CIR) and disease-free survival (DFS) of c-KIT mutated t(8;21)AML patients. .. / Note : MMR: major molecular remission; CT: chemotherapy. HSCT: hematopoietic stem cell transplantation.
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Thecumulative incidence of relapse (CIR) and disease-free survival (DFS) of c-KIT mutated t(8;21)AML patients. ..

Note : MMR: major molecular remission; CT: chemotherapy. HSCT: hematopoietic stem cell transplantation.

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Figure 3
Figure 3.
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Disclosures

No relevant conflicts of interest to declare.

Topics:
hematopoietic stem cell transplantation, mutation, measles-mumps-rubella vaccine, chemotherapy regimen, allopurinol, disease remission, hdac protocol, histone deacetylase, proto-oncogene protein c-kit, runx1 translocation partner 1 protein

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2016 by The American Society of Hematology
2016
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