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Transplantation Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia
Parinda A Mehta1, Mei-Jie Zhang2, Mary Eapen3
1Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Insights
Hematopoietic stem cell transplantation for pediatric hypodiploid acute lymphoblastic leukemia (ALL) shows improved outcomes with advances. However, transplantation in later remission or with fewer chromosomes increases mortality risk.
Area of Science:
- Pediatric Hematology Oncology
- Stem Cell Transplantation
- Leukemia Research
Background:
- Children with hypodiploid acute lymphoblastic leukemia (ALL) exhibit poor prognoses despite current chemotherapy.
- Hematopoietic stem cell transplantation (HSCT) is a potential curative option for high-risk pediatric ALL.
- Understanding factors influencing HSCT outcomes in hypodiploid ALL is critical for improving survival.
Purpose of the Study:
- To evaluate the outcomes of HSCT in a cohort of children with hypodiploid ALL.
- To identify risk factors associated with treatment failure and mortality after HSCT.
- To assess the impact of transplantation timing and patient characteristics on survival.
Main Methods:
- Retrospective analysis of 78 children with hypodiploid ALL undergoing HSCT between 1990 and 2010.
- Data collected included chromosomal counts, remission status at transplantation, donor type, and conditioning regimen.
- Multivariate analysis was used to identify predictors of leukemia-free survival, overall survival, relapse, and treatment-related mortality.
Main Results:
- The 5-year overall survival and leukemia-free survival rates were 56% and 51%, respectively.
- Higher mortality risks were associated with transplantation in second or later remission (CR2+), having ≤ 43 chromosomes, and earlier transplantation period (1990-2000).
- Treatment failure risks were elevated for patients with ≤ 43 chromosomes and those transplanted in the earlier decade.
Conclusions:
- Advances in donor selection and supportive care have improved HSCT outcomes for pediatric hypodiploid ALL.
- Disease-related factors, specifically low chromosome count and transplantation in advanced remission, remain significant predictors of adverse outcomes.
- Further research and risk stratification are needed to optimize HSCT strategies for this challenging leukemia subtype.
Abstract:
Children with hypodiploid acute lymphoblastic leukemia (ALL) have inferior outcomes despite intensive risk-adapted chemotherapy regimens. We describe 78 children with hypodiploid ALL who underwent hematopoietic stem cell transplantation between 1990 and 2010. Thirty-nine (50%) patients had ≤ 43 chromosomes, 12 (15%) had 44 chromosomes, and 27 (35%) had 45 chromosomes. Forty-three (55%) patients underwent transplantation in first remission (CR1) and 35 (45%) underwent transplantation in ≥ second remission (CR2). Twenty-nine patients (37%) received a graft from a related donor and 49 (63%) from an unrelated donor. All patients received a myeloablative conditioning regimen. The 5-year probabilities of leukemia-free survival, overall survival, relapse, and treatment-related mortality for the entire cohort were 51%, 56%, 27%, and 22%, respectively. Multivariate analysis confirmed that mortality risks were higher for patients who underwent transplantation in CR2 (hazard ratio, 2.16; P = .05), with number of chromosomes ≤ 43 (hazard ratio, 2.15; P = .05), and for those who underwent transplantation in the first decade of the study period (hazard ratio, 2.60; P = .01). Similarly, treatment failure risks were higher with number of chromosomes ≤ 43 (hazard ratio, 2.28; P = .04) and the earlier transplantation period (hazard ratio, 2.51; P = .01). Although survival is better with advances in donor selection and supportive care, disease-related risk factors significantly influence transplantation outcomes.
