-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1460 Development of a Modified Prognostic Index for Adult Patients with Acute Lymphoblastic Leukemia

Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Diseases, Lymphoid Malignancies
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Eduardo Cerello Chapchap, MD1*, Ana Luisa Oliveira1*, Maria Eduarda Alonso Joaquim de Carvalho2*, Mireia Morgades3*, Vitor AQ Mauad, MD4*, Davimar Miranda Maciel Borducchi, PhD5, Fabio P. S. Santos, MD6, Jordi Ribera3*, Fabio R. Kerbauy, MD, PhD2*, Josep-Maria Ribera, MD, PhD7 and Nelson Hamerschlak, MD, PhD8

1Hospital Israelita Albert Einstein, Sao Paulo, Brazil
3ICO-Hospital Germans Trias i Pujol, Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
4ABC Medical School, Santo André, Brazil
5CEPHO FMABC (Centro de Estudos e Pesquisa em Hematologia e Oncologia)/ Hospital Estadual Mario Covas - Faculdade de Medicina do ABC, Santo Andre, Brazil
6Hospital Israelita Albert Einstein, Sao Paulo, SP, BRA
7ICO Badalona-Hospital Universitari Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Badalona, Spain
8Albert Einstein Israelite Hospital, Sao Paulo, Brazil

Acute lymphoblastic leukemia (ALL) is associated with inferior overall survival (OS) and progression-free survival (PFS) in adults due to biologic factors and lower tolerance to chemotherapy1,2. Prognostic stratification is essential to guide therapy intensification and indication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, a prognostic index2 integrating measurable residual disease (MRD), white blood count (WBC) and cytogenetic/molecular subtypes has been validated in children and young adults with ALL. However, in adult patients, age, allo-HSCT, other genetic subtypes3 and center reality, may also play role in prognosis. To incorporate new variables to the pre-established prognostic index2, a multicenter PFS analysis was performed to develop a modified/adpated risk score.
Material and Methods: a multicenter (three Brazilian centers and the Spanish PETHEMA AR-03 trial cohort), retrospective study, reviewed medical charts and database of 398 adult patients with Ph-negative ALL (treated between 2003 and 2022), including risk variables: age, WBC count, cytogenetic/molecular classification, MRD, allo-HSCT, clinical outcomes and follow-up. The prognostic index2 was calculated individually, then through multivariate analysis the coefficients (HR/OR) to incorporate age and allo-HSCT to the model have been determined. The methods of logistic regression, Cox model, Kaplan-Meier, log rank, ROC analysis and competitive risk regression were used in the statistical analysis. Subsequently, patients were stratified into 3 prognostic risk categories.
Results: A total of 398 patients, 77% from the PETHEMA protocol and 23% Brazilian centers; 55.2% males; mean age 38.1 years (range 18-60; 67.4% (268) B-ALL; 31.4% (125) T-ALL; 1.2% (5) biphenotypic ALL. median WBC 22.4x109/L; 8.9% with central nervous system involvement; 22.9% high risk cytogenetics. Regarding treatment, 93.9% (373) received pediatric-inspired protocols (AR-03, GRAALL, CALGB, St. Jude TOTALXVI), 6.1% (26) (Hypercvad and others). Regarding the response, 83.3% (309/371) achieved complete remission (CR); CR rate was higher in pediatric inspired versus other protocols: 84.6% vs 57.9% (p 0.006). 45.6% (127/278) reached MRD-neg status after induction and 71.4% (125/175) after consolidation; 21.7% (67/309) underwent allo-HSCT in first remission. After a median follow-up of 3.9 years, 4-year-OS was 42.1% (95%CI 47.2-36.8%) and PFS was 33.4% (95%CI 38.5-28.4%). Cumulative incidences of relapse and non-relapse mortality were: 38.0% and 27.6%, respectively. In multivariate analysis, both allo-HSCT (OR:0.36 95%CI 0.19-0.66 p<0.001) and original2 prognostic index (OR:2.47 95%CI:1.71-3.55 p <0.001) predicted significantly PFS, so allo-HSCT coefficient has been determined and incorporated to the model. According to this modified prognostic index, patients were stratified into 3 risk groups: low (100/285, 35.1%), intermediate (93/285, 32.6%) and high (92/285, 32.3%) high. At 4-years, PFS was significantly superior in low-risk group (55.9% - 95% CI 65.8-44.5%) compared to the intermediate-risk group (37.3% - 95%CI 47.5-27.1%) and high-risk group (182% - 95%CI 27.0-10.8%), p <0.001. Conclusion: The incorporation of the main risk factors in ALL and the role of allo-HSCT into prognostic index for adults can adequately stratify the PFS of patients into 3 risk categories and could assist in clinical decision-making.


  1. Fernandes da Silva Junior W, Medina AB, Yamakawa PE, Buccheri V, Velloso EDRP, Rocha V. Treating Adult Acute Lymphoblastic Leukemia in Brazil-Increased Early Mortality Using a German Multicenter Acute Lymphoblastic Leukemia-based regimen. Clin Lymphoma Myeloma Leuk. 2018 Jun;18(6):e255-e259. doi: 10.1016/j.clml.2018.03.001. Epub 2018 Mar 14. PMID: 29605423.
  2. Amir Enshaei , David O'Connor , Jack Bartram , Jeremy Hancock , Christine J. Harrison , Rachael Hough , Sujith Samarasinghe , Monique L. den Boer , Judith M. Boer , Hester A. de Groot-Kruseman , Hanne V. Marquart , Ulrika Noren-Nystrom , Kjeld Schmiegelow , Claire Schwab , Martin A. Horstmann , Gabriele Escherich , Mats Heyman , Rob Pieters , Ajay Vora , John Moppett, Anthony V. Moorman; A validated novel continuous prognostic index to deliver stratified medicine in pediatric acute lymphoblastic leukemia. Blood 2020; 135 (17): 1438–1446. doi: https://doi.org/10.1182/blood.2019003191

Disclosures: Ribera: Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Takeda: Consultancy; AMGEN: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

*signifies non-member of ASH