Genetics and MRD for therapy allocation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia
Abstract
In adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) genetic risk is usually combined with measurable residual disease (MRD) assignment to consolidation therapy. However, this combination is not uniform across trials and centralized assessment is not always performed. This study analyzed patients' outcomes using centrally assessed MRD and genetics. Patients with high genetic risk (HGR), those who required two induction cycles for complete remission (CR), and CR patients with end-of-induction (EOI) MRD ≥0.01% were assigned to allogeneic hematopoietic stem cell transplant (alloHSCT), while the remaining patients were assigned to delayed consolidation and maintenance. HGR for B-ALL included KMT2A rearrangements, low hypodiploidy and age >35 years, homozygous TP53 mutations/deletions, or concomitant IKZF1 and CDKN2A/B deletions. HGR in T-ALL included absence of NOTCH1/FBXW7 mutations and/or K/NRAS or PTEN alterations. Patients with early T-ALL (ETP) received a different induction regimen, and all were assigned to alloHSCT. Median (range) age of 436 patients was 39 (18-60) years, 332 with B-lineage ALL and 104 T-ALL. By intention to treat, 243 non-ETP patients (61%) were assigned to alloHSCT and 157 (39%) to CT. The 3-year overall survival (OS) probability (95% CI) was 64% (58%-69%). For patients with CR and EOI MRD<0.01% without HGR (n=109), the OS probability was 81% (70%-89%), compared with 50% (34%-63%) for MRD-negative patients with HGR (n=64). In patients with ETP-ALL the probability of 3-year OS was 61% (37%-79%). The combination of genetics and MRD allows accurate identification of adult Ph- ALL patients candidates to alloHSCT or chemotherapy. The trial was registered at www.ClinicalTrials.gov: NCT04179929
Article Details
Authors (54)
Josep-Maria Ribera
Hematology Department. ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
Anna Torrent
Hematology Department. ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
Mireia Morgades
Hematology Department. ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
Susana Barrena
Centro de Investigación del Cáncer (IBMCC-CSIC/USAL-IBSAL); Servicio de Citometría (NUCLEUS), Departamento de Medicina, Universidad de Salamanca, Salamanca; Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC), Instituto de Salud Carlos III, Madrid, Spain
Jordi Ribera
Josep Carreras Leukemia Research Institute (IJC), Badalona, Spain
Eulalia Genesca
Josep Carreras Leukemia Research Institute (IJC), Badalona, Spain
José González-Campos
Hematology Department. Hospital Universitario Virgen del Rocío. Instituto de Biomedicina de Sevilla (IBIS)/CSIC/CIBERONC. Universidad de Sevilla, Sevilla, Spain
Nuria Martínez-Cibrian
Hematology Department. Hospital Clínic, Barcelona, Spain
Pau Montesinos
Hospital Universitari i Politecnic La Fe, Valencia, Spain
Alberto Hernández Sánchez
Hematology Department. Hospital Universitario de Salamanca, IBSAL, IBMCC, CSIC, Centro de Investigación del Cáncer, Salamanca, Spain
Pere Barba
Hematology Department. Hospital Universitari Vall d'Hebron, Barcelona, Spain
Edgar Zapico
Biochemical Department. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Ricardo Sánchez
Hematology Department. Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12) Madrid, Spain
Andrés Novo
Hematology Department. Hospital Son Espases, Palma de Mallorca, Spain
Marta Sitges
Clara Maluquer Artigal
Hematology Department. ICO-Duran i Reynals, L'Hospitalet de Llobregat, Spain
Esperanza Such
Laboratory of Cytogenetics and Molecular Biology. Hospital Universitari i Politècnic La Fe, Valencia, Spain
Carmen Botella
Hematology Department. Hospital General Universitario Dr. Balmis, Alicante, Spain
Maria Paz Queipo de Llano
Hematology Department. Hospital Universitario Virgen de la Victoria, Málaga, Spain
Monica Cabrero
Hematology Department. Hospital Universitario de Salamanca, Salamanca, Spain
Ana Vicent
Hematology Department. ICO-Hospital Universitari Joan XXIII, Tarragona, Spain
Paula Lopez de Ugarriza
Hematology Department. Hospital Universitario Central de Asturias, Oviedo, Spain
Mar Tormo
Hospital Clinico Universitary. INCLIVA Research Institute, Valencia 46010, Spain
Bernardo-Javier González-González
Hematology Department. Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
Irene Garcia-Cadenas
Hematology Department. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Carlos Rodríguez-Medina
Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas De Gran Canaria, Spain
Pilar Martinez Sanchez
Hematology Department. Hospital Universitario 12 de Octubre, Madrid, Spain
Arancha Bermúdez
Hematology Department. Hospital Universitario Marqués de Valdecilla, Santander, Spain
Ignacio Gómez-Centurión
Hematology Department. Hospital General Universitario Gregorio Marañón, Madrid, Spain
Maria Herrero-Garcia
Centro de Investigación del Cáncer (IBMCC-CSIC/USAL-IBSAL); Servicio de Citometría (NUCLEUS), Departamento de Medicina, Universidad de Salamanca, Salamanca; Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC), Instituto de Salud Carlos III, Madrid, Spain
Juana Ciudad
Centro de Investigación del Cáncer (IBMCC-CSIC/USAL-IBSAL); Servicio de Citometría (NUCLEUS), Departamento de Medicina, Universidad de Salamanca, Salamanca; Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC), Instituto de Salud Carlos III, Madrid, Spain
Josgrey Navas-Acosta
Hematology Department. Hospital Universitario de Salamanca, IBSAL, IBMCC, CSIC, Centro de Investigación del Cáncer, Salamanca, Spain
Lourdes Hermosín
Servicio Hematología, Hospital de Jerez, Jerez de la Frontera, Jerez de la Frontera, Cadiz, Spain
Josefina Serrano
University Hospital Reina Sofia. IMIBIC. UCO, Cordoba, Spain
José-Ángel Raposo-Puglia
Hematology Department. Hospital Puerta del Mar, Cádiz, Spain
Laura Solán
Verónica Roldán-Galiacho
Hematology Department. Hospital Universitario de Cruces, Barakaldo, Spain
Almudena de Laiglesia
Hematology Department. Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
Lucía Gómez-Pérez
Hematology Department. Hospital del Mar, Barcelona, Spain
María Solé-Rodríguez
Department of Haematology of Hospital Juan Ramón Jiménez, Huelva, Huelva, Spain
María-Soledad Casado
Hematology Department. Hospital Universitario de Badajoz, Badajoz, Spain
Laura Llorente Gonzalez
Hematology Department. Hospital Universitario HM Sanchinarro, Madrid, Spain
Daniel Barrios Decoud
Hematology Department. Hospital Regional Universitario de Málaga, Málaga, Spain
Ferrán Vall-llovera
Hematology Department. Hospital Universitari Mútua Terrassa, Terrassa, Spain
Jesús-Lorenzo Algarra
Hospital General de Albacete, Albacete, Spain
Lourdes Amador
Hematology Department. Complejo Hospitalario Pontevedra, Pontevedra, Spain
Raimundo García-Boyero
Hospital General Universitario de Castellón, Castellón, Spain
Antònia Cladera
Hematology Department. Hospital Son Llàtzer, Palma de Mallorca, Spain
Juan Miguel Bergua Burgues
Hospital San Pedro de Alcántara. Cáceres, Caceres, Spain
Maria J José Calasanz
UNIVERSITY OF NAVARRA, Pamplona, Spain
Isabel Granada
Hematology Department. ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute (IJC), Universitat Autònoma de Barcelona, Badalona, Spain
Evarist Feliu
Josep Carreras Leukemia Research Institute (IJC), Badalona, Spain
Jesús-María Hernández-Rivas
Departamento de Medicina, Hospital Universitario de Salamanca, IBSAL, Centro de Investigación del Cáncer, IBMCC, CSIC, Universidad de Salamanca, Salamanca, Spain
Alberto Orfao