Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group
Por:
Ribera, JM, Garcia, O, Moreno, MJ, Barba, P, Garcia-Cadenas, I, Mercadal, S, Montesinos, P, Barrios, M, Gonzalez-Campos, J, Martinez-Carballeira, D, Gil, C, Ribera, J, Vives, S, Novo, A, Cervera, M, Serrano, J, Lavilla, E, Abella, E, Tormo, M, Amigo, ML, Artola, MT, Genesca, E, Bravo, P, Garcia-Belmonte, D, Garcia-Guinon, A, Hernandez-Rivas, JM, Feliu, E
Publicada:
15 ago 2019
Resumen:
Background Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763). Methods Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard-dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes. Results Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo-HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease-free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months [P = .05] and 28.7 months vs 11.5 months [P = .05] for DFS and OS, respectively). Conclusions Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.
Filiaciones:
Ribera, JM:
Autonomous Univ Barcelona, Josep Carreras Leukemia Res Inst, ICO Badalona Hosp Germans Trias & Pujol, Dept Clin Hematol, Badalona, Spain
Garcia, O:
Autonomous Univ Barcelona, Josep Carreras Leukemia Res Inst, ICO Badalona Hosp Germans Trias & Pujol, Dept Clin Hematol, Badalona, Spain
Moreno, MJ:
Hosp Virgen Victoria, Dept Hematol, Malaga, Spain
Barba, P:
Autonomous Univ Barcelona, Vall Hebron Univ Hosp, Dept Hematol, Barcelona, Spain
Garcia-Cadenas, I:
Hosp Santa Creu & Sant Pau, Dept Hematol, Barcelona, Spain
Mercadal, S:
ICO Hosp Duran & Reynals, Dept Hematol, Lhospitalet De Llobregat, Catalonia, Spain
Montesinos, P:
Le Fe Univ & Polytech Hosp, Dept Hematol, Valencia, Spain
Barrios, M:
Carlos Haya Hosp, Dept Hematol, Malaga, Spain
Gonzalez-Campos, J:
Virgen del Rocio Univ Hosp, Dept Hematol, Seville, Spain
Martinez-Carballeira, D:
Cent Hosp Asturias, Dept Hematol, Oviedo, Spain
Gen Univ Hosp Alicante, Dept Hematol, Alicante, Spain
Gil, C:
Gen Univ Hosp Alicante, Dept Hematol, Alicante, Spain
Ribera, J:
Autonomous Univ Barcelona, Josep Carreras Leukemia Res Inst, ICO Badalona Hosp Germans Trias & Pujol, Dept Clin Hematol, Badalona, Spain
Vives, S:
Autonomous Univ Barcelona, Josep Carreras Leukemia Res Inst, ICO Badalona Hosp Germans Trias & Pujol, Dept Clin Hematol, Badalona, Spain
Novo, A:
Son Espases Hosp, Dept Hematol, Palma De Mallorca, Spain
Cervera, M:
ICO Hosp Joan XXIII, Dept Hematol, Tarragona, Spain
Serrano, J:
Reina Sofia Hosp, Dept Hematol, Cordoba, Spain
Lavilla, E:
Lucus Augusti Hosp, Dept Hematol, Lugo, Spain
Abella, E:
Mar Hosp, Dept Hematol, Barcelona, Spain
Clin Hosp, Dept Hematol, Valencia, Spain
Tormo, M:
Clin Hosp, Dept Hematol, Valencia, Spain
Amigo, ML:
Morales Meseguer Univ, Gen Hosp, Dept Hematol, Murcia, Spain
Artola, MT:
Donostia Univ Hosp, Dept Hematol, San Sebastian, Spain
Genesca, E:
Autonomous Univ Barcelona, Josep Carreras Leukemia Res Inst, ICO Badalona Hosp Germans Trias & Pujol, Dept Clin Hematol, Badalona, Spain
Bravo, P:
Fuenlabrada Univ Hosp, Dept Hematol, Madrid, Spain
Garcia-Belmonte, D:
La Zarzuela Hosp, Dept Hematol, Madrid, Spain
Garcia-Guinon, A:
Arnau de Vilanova Hosp, Dept Hematol, Lleida, Spain
Hernandez-Rivas, JM:
Univ Hosp Salamanca, Dept Hematol, Salamanca, Spain
Feliu, E:
Autonomous Univ Barcelona, Josep Carreras Leukemia Res Inst, ICO Badalona Hosp Germans Trias & Pujol, Dept Clin Hematol, Badalona, Spain
Bronze
|