Josep-Maria Ribera1, Albert Oriol2, Mireia Morgades2, Pau Montesinos2, Josep Sarrà2, José González-Campos2, Salut Brunet2, Mar Tormo2, Pascual Fernández-Abellán2, Ramon Guàrdia2, María-Teresa Bernal2, Jordi Esteve2, Pere Barba2, María-José Moreno2, Arancha Bermúdez2, Antonia Cladera2, Lourdes Escoda2, Raimundo García-Boyero2, Eloy Del Potro2, Juan Bergua2, María-Luz Amigo2, Carlos Grande2, María-José Rabuñal2, Jesús-María Hernández-Rivas2, Evarist Feliu2. 1. Josep-Maria Ribera, Albert Oriol, Mireia Morgades, and Evarist Feliu, Institut Català d'Oncologia-Hospital Germans Trias i Pujol-Jose Carreras Research Institute; Salut Brunet, Hospital de Sant Pau; Jordi Esteve, Hospital Clínic; Pere Barba, Hospital Vall d'Hebron, Barcelona; Pau Montesinos, Hospital Universitario La Fe; Mar Tormo, Hospital Clínico, Valencia; Josep Sarrà, Institut Català d'Oncologia-Hospital Duran i Reynals, L'Hospitalet de Llobregat; José González-Campos, Hospital Universitario Virgen del Rocío, Sevilla; Pascual Fernández-Abellán, Hospital General, Alicante; Ramon Guàrdia, Institut Català d'Oncologia-Hospital Josep Trueta, Girona; María-Teresa Bernal, Hospital Central de Asturias, Oviedo; María-José Moreno, Hospital Virgen de la Victoria, Málaga; Arancha Bermúdez, Hospital Marqués de Valdecilla, Santander; Antonia Cladera, Hospital Son Llàtzer, Palma de Mallorca; Lourdes Escoda, Hospital Joan XXIII, Tarragona; Raimundo García-Boyero, Hospital General, Castellón; Eloy del Potro, Hospital Clínico San Carlos; Carlos Grande, Hospital Doce de Octubre, Madrid; Juan Bergua, Hospital San Pedro de Alcántara, Cáceres; María-Luz Amigo, Hospital Morales Meseguer, Murcia; María-José Rabuñal, Hospital Xeral, Santiago de Compostela; and Jesús-María Hernández-Rivas, Hospital Universitario-Instituto del Cáncer, Universidad de Salamanca, Salamanca, Spain. jribera@iconcologia.net. 2. Josep-Maria Ribera, Albert Oriol, Mireia Morgades, and Evarist Feliu, Institut Català d'Oncologia-Hospital Germans Trias i Pujol-Jose Carreras Research Institute; Salut Brunet, Hospital de Sant Pau; Jordi Esteve, Hospital Clínic; Pere Barba, Hospital Vall d'Hebron, Barcelona; Pau Montesinos, Hospital Universitario La Fe; Mar Tormo, Hospital Clínico, Valencia; Josep Sarrà, Institut Català d'Oncologia-Hospital Duran i Reynals, L'Hospitalet de Llobregat; José González-Campos, Hospital Universitario Virgen del Rocío, Sevilla; Pascual Fernández-Abellán, Hospital General, Alicante; Ramon Guàrdia, Institut Català d'Oncologia-Hospital Josep Trueta, Girona; María-Teresa Bernal, Hospital Central de Asturias, Oviedo; María-José Moreno, Hospital Virgen de la Victoria, Málaga; Arancha Bermúdez, Hospital Marqués de Valdecilla, Santander; Antonia Cladera, Hospital Son Llàtzer, Palma de Mallorca; Lourdes Escoda, Hospital Joan XXIII, Tarragona; Raimundo García-Boyero, Hospital General, Castellón; Eloy del Potro, Hospital Clínico San Carlos; Carlos Grande, Hospital Doce de Octubre, Madrid; Juan Bergua, Hospital San Pedro de Alcántara, Cáceres; María-Luz Amigo, Hospital Morales Meseguer, Murcia; María-José Rabuñal, Hospital Xeral, Santiago de Compostela; and Jesús-María Hernández-Rivas, Hospital Universitario-Instituto del Cáncer, Universidad de Salamanca, Salamanca, Spain.
Abstract
PURPOSE: Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation. PATIENTS AND METHODS: Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4). RESULTS: Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10(-3) after induction and ≥ 5 × 10(-4) after early consolidation) as the only prognostic factor for DFS and OS. CONCLUSION: Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.
PURPOSE: Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation. PATIENTS AND METHODS: Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10(-4). RESULTS: Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10(-3) after induction and ≥ 5 × 10(-4) after early consolidation) as the only prognostic factor for DFS and OS. CONCLUSION: Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.
Authors: Olga Sala Torra; Megan Othus; David W Williamson; Brent Wood; Ilan Kirsch; Harlan Robins; Lan Beppu; Margaret R O'Donnell; Stephen J Forman; Frederick R Appelbaum; Jerald P Radich Journal: Biol Blood Marrow Transplant Date: 2017-01-03 Impact factor: 5.742
Authors: Elias Jabbour; Nicholas J Short; Jeffrey L Jorgensen; Musa Yilmaz; Farhad Ravandi; Sa A Wang; Deborah A Thomas; Joseph Khoury; Richard E Champlin; Issa Khouri; Partow Kebriaei; Susan M O'Brien; Guillermo Garcia-Manero; Jorge E Cortes; Koji Sasaki; Courtney D Dinardo; Tapan M Kadia; Nitin Jain; Marina Konopleva; Rebecca Garris; Hagop M Kantarjian Journal: Cancer Date: 2016-09-07 Impact factor: 6.860
Authors: Farhad Ravandi; Jeffrey L Jorgensen; Susan M O'Brien; Elias Jabbour; Deborah A Thomas; Gautam Borthakur; Rebecca Garris; Xuelin Huang; Guillermo Garcia-Manero; Jan A Burger; Alessandra Ferrajoli; William Wierda; Tapan Kadia; Nitin Jain; Sa A Wang; Sergei Konoplev; Partow Kebriaei; Richard E Champlin; Deborah McCue; Zeev Estrov; Jorge E Cortes; Hagop M Kantarjian Journal: Br J Haematol Date: 2015-10-22 Impact factor: 6.998