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Published on: October 11, 2018
[Prognostic analysis of children with Philadelphia chromosome-like acute lymphoblastic leukemia common genes]
1Department of Hematology and Oncology, Children's Hospital, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Insights
Children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes are diagnosed at an older age and have a poorer prognosis. Bone marrow minimal residual disease (MRD) status after first induction is a key independent prognostic factor.
Area of Science:
- Pediatric Oncology
- Hematology
- Genetics
Context:
- Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype of B-cell ALL.
- Identifying specific genetic alterations and their clinical impact is crucial for treatment stratification.
Purpose:
- To analyze the clinical characteristics and prognosis of pediatric Ph-like ALL with common gene alterations.
- To identify independent prognostic factors in this patient cohort.
Summary:
- This retrospective study compared 56 children with Ph-like ALL common genes to 69 children with other high-risk B-ALL.
- Ph-like ALL patients were older, had higher white blood cell counts, and a significantly lower 3-year overall survival rate.
- IK6 positivity was associated with better event-free survival, while bone marrow minimal residual disease (MRD) non-negativity after first induction was an independent negative prognostic factor.
Impact:
- Provides insights into the clinical presentation and outcomes of pediatric Ph-like ALL.
- Highlights the prognostic significance of MRD in Ph-like ALL, guiding future therapeutic strategies.
- Contributes to a better understanding of genetic drivers and their role in disease progression.
Abstract:
Objective: To summarize the clinical data and prognosis of children with Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) common genes. Methods: This was a retrospective cohort study.Clinical data of 56 children with Ph-like ALL common gene cases (Ph-like ALL positive group) treated from January 2017 to January 2022 in the First Affiliated Hospital of Zhengzhou University, Henan Children's Hospital, Henan Cancer's Hospital and Henan Provincial People's Hospital were collected, 69 children with other high-risk B cell acute lymphoblastic leukemia (B-ALL) at the same time and the same age were selected as the negative group. The clinical characteristics and prognosis of two groups were analyzed retrospectively. Comparisons between groups were performed using Mann-Whitney U test and χ2 test. Kaplan-Meier method was used for survival curve, Log-Rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognosis analysis. Results: Among 56 Ph-like ALL positive patients, there were 30 males and 26 females, and 15 cases were over 10 years old. There were 69 patients in Ph-like ALL negative group. Compared with the negative group, the children in positive group were older (6.4 (4.2, 11.2) vs. 4.7 (2.8, 8.4) years), and hyperleukocytosis (≥50×109/L) was more common (25% (14/56) vs. 9% (6/69)), the differences were statistically significant (both P<0.05). In the Ph-like ALL positive group, 32 cases were positive for IK6 (1 case was co-expressed with IK6 and EBF1-PDGFRB), 24 cases were IK6-negative, of which 9 cases were CRLF2 positive (including 2 cases with P2RY8-CRLF2, 7 cases with CRLF2 high expression), 5 cases were PDGFRB rearrangement, 4 cases were ABL1 rearrangement, 4 cases were JAK2 rearrangement, 1 case was ABL2 rearrangement and 1 case was EPOR rearrangement. The follow-up time of Ph-like ALL positive group was 22 (12, 40) months, and 32 (20, 45) months for negative group. The 3-year overall survival (OS) rate of positive group was significantly lower than the negative group ((72±7) % vs. (86±5) %, χ=4.59, P<0.05). Compared with the 24 IK6-negative patients, the 3-year event free survival (EFS) rate of 32 IK6 positive patients was higher, the difference was statistically significant ((88±9) % vs. (65±14) %, χ=5.37, P<0.05). Multivariate Cox regression analysis showed that the bone marrow minimal residual disease (MRD) not turning negative at the end of first induction (HR=4.12, 95%CI 1.13-15.03) independent prognostic risk factor for patient with Ph-like ALL common genes. Conclusions: Children with Ph-like ALL common genes were older than other high-risk B-ALL patients at diagnosis, with high white blood cells and lower survival rate. The bone marrow MRD not turning negative at the end of first induction were independent prognostic risk factor for children with Ph-like ALL common gene.
