TLS-ERG fusion gene resulting from translocation changes involving chromosomes 16 and 21 is a rare genetic event mostly observed in acute myeloid leukemia (AML). AML with TLS-ERG has unique clinical and morphological features and showed poor prognosis and a high relapse rate. However, many clinical aspects of this type of leukemia still remain unknown. Here, we report the clinical features and outcome of 22 leukemia patients (20 AML and 2 B-ALL) with TLS-ERG fusion gene. The median age of patients was 6 (2-35) years old. 12 patients were males and 10 were females. The median WBC count at diagnosis was 26.54 (1.3-110.8)X109/L.
TLS-ERG is tightly associated with extramedullary disease (EMD), complex chromosome abnormalities, and high risk gene mutations. 9/22 (40.9%) cases had complex chromosome abnormalities, 8/22 (36.4%) cases had EMDs, and a large proportion of cases had hematological malignancies gene mutations such as IKZF1, TET2, WT1, PHF6 and NOTCH2. 9 cases in this study had been examined for congenital inherited diseases (Familial hemophagocytic lymphohistiocytosis, FHLH, Fanconi anemia, FA and Dyskeratosis congenital, DC) gene mutations such as FANCD2, FANCG, FANCA, STXBP2, UNC13D, LAMP1 and LYST, and 7/9 (77.8%) cases had positive results. The details are summarized in Table I.
We firstly evaluated the general outcome of these patients. Excluding B-ALL patients, 7/20 (35%) cases achieved complete remission (CR) after induction. The median CR, complete molecular remission (CMR), and overall survival (OS) time of the 20 cases was 7 (0-16), 3 (0-14), and 12 (1-36) months. The 6 months relapse free survival (RFS) of EMD and non-EMD patients was 75% and 83.3% (P=0.017, Figure 1).
We evaluated the impact of HCT on the outcome of these patients.11/20 AML received allo-HCT, but 9/20 did not. In non-HCT group, the median CR time was 8 (0-29) months. 7/9 cases achieved CR, 3/9 cases achieved CMR, and all cases had disease progression. The median OS time was 11 (1-76) months. In HCT group, 9/11 cases underwent haploidentical HCT (HID-HCT), and 2/11 underwent HLA-matched unrelated donor HCT (URD-HCT). The median OS time was 19 (9-36) months. 1 year OS in non-HCT and HCT group was 62.5% and 90%, respectively (P=0.026, Figure 2), but 6 month RFS in non-HCT and HCT group was 55.6% and 100% (P=0.192), without statistical significance.
We analyzed the effect of diverse clinic factors on the outcome of HCT. At the time of HCT, 1/11 case was NR, 10/11 cases were CR, 7/10 CR cases were not detected blasts by FCM, and 6/10 CR cases were CMR. 6 months RFS of CR and NR case was 67.5% and 0, respectively (P=0.034). 6 months RFS of FCM+ and FCM- cases was 50% and 71.4% (P=0.403). 6 months RFS of CMR and non-CMR cases was 66.7% and 60% (P=0.671). There are 5 EMD cases among the 11 cases that underwent HCT, and 6 months RFS of HCT cases with or without EMDs was 33.3% and 71.4%, respectively (P=0.204). Among the 8 TLS-ERG+ AML patients with EMD, 6/8 cases achieved CR after induction, and 5/8 cases underwent HCT after CR, the 6 months RFS of EMDs with or without HCT was 100% and 33.3% (P=0.203). Among the 12 TLS-ERG+ AML patients without EMD, 10/12 cases achieved CR after induction, and 6/12 cases underwent HCT after CR, the 6 months RFS of them with or without HCT was 100% and 66.7%, respectively (P=0.176).
In conclusion, we found TLS-ERG is tightly associated with complex chromosome abnormalities and high risk gene mutations including IKZF1, TET2, WT1, PHF6, FANCD2, FANCG, FANCA, which might partially explain the overall poor prognosis of TLS-ERG patients. The leukemia burden before HCT and EMD has negative impact on the outcome of TLS-ERG patients. HCT could prolong the OS of the patients, but could not overcome the poor prognosis of TLS-ERG. No matter the patients had EMD or not, the RFS could not be improved by HCT. Our study will be valuable for evaluating the therapeutic regimen and prognosis of AML patients with TLS-ERG fusion gene.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.