Clinical Analysis and Gene Mapping of 12 Children with Therapy-Related Myelodysplastic Syndrome/Acute Leukemia

Objective Retrospectively analyze the clinical characteristics, regimen, prognosis and genetic profiles of the largest single-center therapy-related myelodysplastic syndrome/acute leukemia (t-MDS/AL) in China.

Methods clinical data of all pediatric patients diagnosed with t-MDS/AL since January 1,2018, were retrospectively collected and analyzed.

Results

(1) 12 pediatric t-MDS/AL patients were involved including 5 boys and 7 girls. The median age of primary and secondary tumors were 8 years old (range: 1-13 years) and 11 years old (range: 4-15 years). All patients received chemotherapy/radiotherapy after primary tumor diagnosis, and developed hematologic malignancies 6-71 months later, including 5 cases of t-MDS, 6 cases of t-AML and 1 case of t-ALL among them. Then 3 in 5 cases of t-MDS developed AML in late stage.

(2) All patients fellow up to July 1,2024. one patient received partial remission (PR) after EA induction regimen, but relapsed soon later, then gave up. 2 cases were treated with decitabine chemotherapy all with non-remission (NR). One case was treated with HAD induction regimen and NR. One case was treated with HAG regimen, NR. One case was treated with Decitabine + CAG regimen, NR. One case was treated with HAG + cladribine regimen and achieved complete remission (CR). 1 case was treated with VIA protocol, CR. One case of t-ALL was treated with induction chemotherapy (NR) in CCCG-ALL-2015 regimen. In the transplantation group, there were 6 cases, including 2 cases of direct transplantation without treatment, 3 cases of rescue transplantation with NR status and 1 case of transplantation with CR status, one patient relapsed 6 months after transplantation, and one patient relapsed 2 months after transplantation. In the non-transplantation group, there were 4 cases, 1 case of disease-free survival, 1 case of persistent NR status and 2 cases of death.

(3) The fusion gene of acute leukemia was detected in 10 patients. There were WT1 gene in 6 cases, P2RY8-CRLF2 fusion gene in 1 case, AML1-ETO fusion gene in 2 cases, MLL-AF9 fusion gene in 1 case, FLT3-ITD in 1 case and FLT3-TKD in 1 case.

(4) In the cytogenetics, only 2 cases had normal karyotype, 1 case had complex karyotype with recurrent genetic abnormalities such as t(8; 21), t(9; 11) and other chromosomal abnormalities such as 45, x,-y, etc. Another common abnormal karyotype was -17.

(5) the second-generation sequencing showed that there were 2 mutations in TP53, 2 mutations in KMT2D, 2 mutations in RUNX1,2 mutations in NRAS and 2 mutations in FLT3.

Conclusion Therapy-related hematologic malignancy is a rare disease which is caused by lots of factors. The remission rate of traditional chemotherapy is low and the mortality is high. Reducing the overlap of chemotherapy drugs, choosing new drugs, or performing transplantation directly and as soon as possible may improve the prognosis.

No relevant conflicts of interest to declare.