High Transcript Level of FLT3 Associated with High Risk of Relapse in Pediatric Acute Myeloid Leukemia

Key Points Higher allelic burden at day 21 of post-HCT is associated with higher risk of relapse and mortality. Longitudinal tracking of AML patients receiving HCT is feasible and provides clinically relevant information.

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Apoptosis: A biomarker of high-risk phenotype in pediatric acute myeloid leukemia?

International Journal of Laboratory Hematology ◽

10.1111/ijlh.12939 ◽

2018 ◽

Vol 41 (1) ◽

pp. 141-147 ◽

Cited By ~ 1

Author(s):

Anudishi Tyagi ◽

Raja Pramanik ◽

Radhika Bakhshi ◽

Sreenivas Vishnubhatla ◽

Sameer Bakhshi

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Myeloid Leukemia ◽

Pediatric Acute Myeloid Leukemia ◽

Acute Myeloid

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Impact of allogeneic hematopoietic stem cell transplantation on pediatric acute myeloid leukemia of FAB subtypes M4 and M5

10.21203/rs.3.rs-30250/v1 ◽

2020 ◽

Author(s):

Yu-juan Xue ◽

Pan Suo ◽

Yi-fei Cheng ◽

Ai-dong Lu ◽

Yu Wang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

High Risk ◽

Myeloid Leukemia ◽

Risk Groups ◽

Low Risk ◽

Intermediate Risk ◽

Hematopoietic Stem ◽

Pediatric Acute Myeloid Leukemia ◽

Acute Myeloid

Abstract Background: FAB-M4 and M5 are unique subgroups of pediatric acute myeloid leukemia. However, for these patients, few studies have demonstrated the clinical and biological characteristics and efficacy of hematopoietic stem cell transplantation (HSCT), and especially haplo-HSCT. Procedure: We retrospectively evaluated the outcomes of 70 children with FAB-M4/M5 enrolled in our center from January 2013 to December 2017. Results: Of the patients, 32, 23, and 15 were in low-risk, intermediate-risk, and high-risk groups, respectively. T(16;16), inv16/CBFB-MYH11 was the most frequent cytogenetic abnormality. Among detected genetic alterations, WT1 was mutated at the highest frequency, followed by FLT3-ITD, NPM1, and CEBPA. Thirty-three patients received HSCT (haplo-HSCT = 30), of which four, 18, and 11 were in low-risk, intermediate-risk, and high-risk groups, respectively. For all patients, the 3-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 85.3 ± 4.3%, 69.0 ± 5.7%, and 27.9 ± 5.2%, respectively. By multivariate analysis, low-risk stratification predicted superior OS, EFS, and PLT ≤ 50 × 109/L at diagnosis, with FLT3-ITD mutations predicting higher CIR and poorer EFS. In intermediate- and high-risk groups, HSCT was independently associated with higher EFS and lower CIR. With a median post-transplant observation time of 30.0 months, the 3-year OS, EFS, CIR, and non-relapse mortality in the haplo-HSCT group were 74.2 ± 8.6%, 68.3 ± 8.9, 24.6 ± 7.6%, and 6.6 ± 4.1%, respectively. Conclusions: Risk-oriented treatment is important for pediatric FAB-M4/M5. For intermediate- and high-risk groups, HSCT significantly improved survival and haplo-HSCT might be a viable alternative approach.

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Clonal Involvement of the CD34+CD33− Progenitor Population by Leukemic Cells Harboring FLT3/ITD Correlates with High Risk of Relapse in Pediatric Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v106.11.227.227 ◽

2005 ◽

Vol 106 (11) ◽

pp. 227-227

Author(s):

Jessica A. Wright ◽

Todd A. Alonzo ◽

Robert B. Gerbing ◽

William G. Woods ◽

Beverly J. Lange ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Clinical Outcome ◽

Myeloid Leukemia ◽

Poor Clinical Outcome ◽

Free Survival ◽

Allelic Ratio ◽

Risk Of Relapse ◽

Acute Myeloid

Abstract Internal tandem duplication of the FLT3 gene (FLT3/ITD) has been associated with high risk of relapse in acute myeloid leukemia (AML) yet nearly 25–30% of the patients with FLT3/ITD have long-term disease free survival with conventional chemotherapy. We hypothesized that FLT3/ITD AML patients with poor clinical outcome may have disease that involves less mature hematopoietic precursors than patients with favorable outcome. To test this hypothesis, we isolated less mature, CD34+CD33− and more mature, CD34+CD33+ precursor cells from 24 pediatric AML patients enrolled on Children’s Cancer Group clinical trials CCG-2891 and 2961 previously identified as having a FLT3/ITD. Granulocyte/monocyte colonies (CFU-GM) were grown in methylcellulose, harvested, and analyzed for the presence of FLT3/ITD after 14 days of growth. Twenty patients yielded sufficient cells and growth of CFU-GM colonies for analysis. FLT3/ITD was detected in CFU-GM colonies derived from CD34+CD33+ cells in all patient samples (median 80% of colonies tested per patient, range 6–100%). In contrast, FLT3/ITD was detected in CFU-GM colonies derived from CD34+/CD33− cells in only 11 of the 20 patient samples (median 46% of colonies tested per patient, range 6–100%). Of the 9 patient samples without FLT3/ITD involvement of CD34+CD33− colonies, 8 achieved a CR, 6 of whom are long-term survivors, and one patient died of non-leukemic causes. In contrast, of the 11 patients with CD34+CD33− cell involvement, 9 either failed to achieve CR or relapsed after achieving CR, and 2 died of non-leukemic causes. Actuarial progression-free survival at 4 years from diagnosis for the patients with and without FLT3/ITD in the CD34+CD33− population was 0% vs. 68% respectively (p=0.017). As allelic ratio of the FLT3/ITD has been used to define high-risk patients within the FLT3/ITD cohort, we determined the FLT3/ITD allelic ratio in our study population and correlated it with the presence of FLT3/ITD in the CD34+CD33− population. Ten of the 11 (91%) of the patient samples with FLT3/ITD involvement of the progenitor cells had high allelic ratio compared to 5 of 9 (56%) of the patients without early cell involvement. Together these data suggest that clonal dominance of FLT3/ITD containing leukemia cells at the CD34+CD33− stage of hematopoietic development is correlated with a high risk of relapse. Further studies are required to determine whether clonal dominance at this hematopoietic stage is a variable that, independent of high allelic ratio, accounts for the poor clinical outcome seen in a subset of FLT3/ITD positive AML patients.

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