A robust and validated integrated prognostic index for defining risk groups in adult acute lymphoblastic leukemia : an EWALL collaborative study
Enshaei, Amir (Newcastle University)
Joy, Melvin (Newcastle University)
Butler, Ellie (Newcastle University)
Kirkwood, Amy A. (University College London)
Morgades, Mireia (Fondazione Gruppo Italiano Malattie Ematologiche dell'Adulto)
Pavoni, Chiara (ASST Papa Giovanni XXIII (Bergamo, Itàlia))
Morgades, Mireia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Harrison, Christine J. (Newcastle University)
Foà, Renato (Università degli Studi di Roma "La Sapienza")
Ribera, Jose-Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Chiaretti, Sabina (Università degli Studi di Roma "La Sapienza")
Bassan, Renato (Santissimi Giovanni and Paolo Hospital)
Fielding, Adele K. (UCL Cancer Institute (Londres, Regne Unit))
Moorman, Anthony V. (Newcastle University)

Data:	2024
Resum:	Risk stratification is crucial to the successful treatment of acute lymphoblastic leukemia (ALL). Although numerous risk factors have been identified, an optimal prognostic model for integrating variables has not been developed. We used individual patient data from 4 contemporary academic national clinical trials, UKALL14, NILG-ALL10/07, GIMEMALAL1913, and PETHEMA-ALL-HR2011, to generate and validate the European Working Group for Adult ALL prognostic index (EWALL-PI), which is based on white blood cell count, genetics, and end of induction minimal residual disease (MRD). Individual patient risk scores were calculated for 778 patients aged 15 to 67 years in complete remission using the validated UKALL-PI formula, applying minor modifications to reflect differences between pediatric and adult ALL. Per-trial analysis revealed that EWALL-PI correlated with relapse and death. Regression analysis revealed that each unit increase in EWALL-PI increased the risk of relapse or death by ~30% with no evidence of heterogeneity across trials or patient subgroups. EWALL-PI-defined risk models outperformed the stratification algorithms used by each trial. Threshold analysis revealed an EWALL-PI threshold that divided patients with B cell and T cell into standard (EWALL-PI <2. 50) and high (EWALL-PI ≥2. 50) risk groups, respectively. Per-trial analysis showed that patients at high risk had a significantly increased relapse rate and inferior survival compared with patients with standard risk (subdistribution hazard ratio for relapse, ranged from 1. 85 to 3. 28; hazard ratio for death, 1. 73 to 3. 03). Subgroup analysis confirmed the robustness of these risk groups by sex, age, white blood cell count, and lineage. In conclusion, we validated an integrated risk model across 4 independent adult ALL clinical trials, demonstrating its utility defining clinically relevant risk groups.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Blood advances, Vol. 8 Núm. 5 (december 2024) , p. 1155-1166, ISSN 2473-9537

DOI: 10.1182/bloodadvances.2023011661
PMID: 38113467

12 p, 1.4 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
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