Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia

Ribera, JM; Morgades, M; Ciudad, J; Montesinos, P; Esteve, J; Genesca, E; Barba, P; Ribera, J; Garcia-Cadenas, I; Moreno, MJ; Martinez-Carballeira, D; Torrent, A; Martinez-Sanchez, P; Monsalvo, S; Gil, C; Tormo, M; Artola, MT; Cervera, M; Gonzalez-Campos, J; Rodriguez, C; Bermudez, A; Novo, A; Soria, B; Coll, R; Amigo, ML; Lopez-Martinez, A; Fernandez-Martin, R; Serrano, J; Mercadal, S; Cladera, A; Gimenez-Conca, A; Penarrubia, MJ; Abella, E; Vall-llovera, F; Hernandez-Rivas, JM; Garcia-Guinon, A; Bergua, JM; de Rueda, B; Sanchez-Sanchez, MJ; Serrano, A; Calbacho, M; Alonso, N; Mendez-Sanchez, JA; Garcia-Boyero, R; Olivares, M; Barrena, S; Zamora, L; Granada, I; Lhermitte, L; Feliu, E; Orfao, A


The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (+/- 95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% +/- 7%, 49% +/- 7%, and 40% +/- 6%, respectively, with CIR and OS rates of 45% +/- 8% and 59% +/- 9% for patients assigned to chemotherapy and of 40% +/- 12% and 38% +/- 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance.

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