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Soluble l-selectin (sCD62L) in relapsed childhood acute lymphoblastic leukaemia
Ralf Herold1, Dietger Stibenz, Reinhard Hartmann
1Paediatric Oncology-Haematology and Neonatology, Otto-Heubner-Centre for Paediatric and Adolescent Medicine, Charité, Virchow Medical Centre, Humboldt University, Berlin, Germany. ralf.herold@charite.de
Insights
Soluble L-selectin (sCD62L) levels in children with relapsed acute lymphoblastic leukemia (ALL) can predict outcomes. Low sCD62L indicates a worse event-free survival, especially in high-risk patients, suggesting its use in risk stratification.
Area of Science:
- Pediatric Oncology
- Hematology
- Immunology
Background:
- Relapsed acute lymphoblastic leukemia (ALL) in children presents significant treatment challenges.
- Understanding prognostic markers is crucial for optimizing therapeutic strategies.
Purpose of the Study:
- To investigate the association between plasma soluble L-selectin (sCD62L) concentrations and outcomes in pediatric ALL patients at first relapse.
- To evaluate the potential of sCD62L as a biomarker for risk stratification in this patient cohort.
Main Methods:
- Analysis of plasma sCD62L levels in 193 children with first relapsed ALL treated under ALL-REZ BFM 95/96 trials.
- Correlation of sCD62L levels (low, normal, high) with clinical factors, adverse events, and event-free survival (EFS).
- Stratification of patients into worst-prognosis (S3/S4) and non-worst-prognosis groups.
Main Results:
- Low sCD62L was observed in 33% and high sCD62L in 19% of patients, independent of remission duration, sex, or BCR-ABL fusion.
- High sCD62L correlated with circulating blasts and T-cell phenotype.
- Increased adverse events were noted in patients with very low or very high sCD62L levels compared to normal levels (P=0.018).
- In worst-prognosis patients, low sCD62L was associated with significantly decreased EFS probability and duration (P=0.01).
- In non-worst-prognosis patients, sCD62L levels did not significantly impact EFS.
Conclusions:
- Low plasma sCD62L may serve as a marker for malignant blasts replacing normal hematopoietic cells.
- Plasma sCD62L levels can be a valuable tool for risk-adapted stratification in children with first relapse of ALL, particularly those with worst prognosis.
Abstract:
Soluble l-selectin (sCD62L) plasma concentrations at diagnosis and outcome were investigated in 193 children at first relapse of acute lymphoblastic leukaemia (ALL) after treatment according to the Berlin-Frankfurt-Münster relapsed ALL multicentre trials, ALL-REZ BFM 95 and 96. sCD62L was low (< fifth paediatric reference percentile) in 63 (33%) and high (> 95th percentile) in 36 (19%) children, and was independent of remission duration, sex, BCR-ABL fusion or extramedullary disease. High sCD62L was associated with circulating blasts and T-cell phenotype. More initial adverse events occurred in children with high and low levels of sCD62L (23 out of 99) than in those with normal levels (9 out of 94, P = 0.018). Among 75 worst-prognosis patients (risk groups S3/S4, isolated bone marrow relapse occurring less than 6 months after elective cessation of front-line therapy, or T-cell phenotype with bone marrow involvement), 27 had low sCD62L and decreased event-free survival (EFS) probability (PEFS5 = 0.09 at 5 years) and duration (219 d) compared with normal sCD62L (29 out of 75, PEFS5 = 0.24, 640 d, P = 0.01). Low (44 out of 118), normal (72 out of 118), and high (19 out of 118) sCD62L non-S3/S4 patients fared similarly (average PEFS5 = 0.45, 1369 d; P = 0.5). Low sCD62L may be a marker of malignant blasts replacing normal sCD62L-producing haematopoietic cells. In children with first relapse of ALL and worst prognosis, plasma sCD62L may be useful for risk-adapted stratification.
