title: Achieving Molecular Remission before Allogeneic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Impact on Relapse and Long-Term Outcome.
abstract: Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials. MRD evaluation before transplantation was available for 65 of the 73 patients who underwent an alloHSCT in CR1. A complete or major molecular response at time of conditioning was achieved in 24 patients (37%), whereas 41 (63%) remained carriers of any other positive MRD level in the bone marrow. MRD negativity at time of conditioning was associated with a significant benefit in terms of risk of relapse at 5 years, with a relapse incidence of 8% compared with 39% for patients with MRD positivity (P = .007). However, thanks to the post-transplantation use of tyrosine kinase inhibitors (TKIs), disease-free survival was 58% versus 41% (P = .17) and overall survival was 58% versus 49% (P = .55) in MRD-negative compared with MRD-positive patients, respectively. The cumulative incidence of nonrelapse mortality was similar in the 2 groups. Achieving a complete molecular remission before transplantation reduces the risk of leukemia relapse even though TKIs may still rescue some patients relapsing after transplantation.
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. Electronic address: flussana@asst-pg23.it.
authors: Federico
authors: F
authors: Lussana
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Tamara
authors: T
authors: Intermesoli
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Francesca
authors: F
authors: Gianni
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Cristina
authors: C
authors: Boschini
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Arianna
authors: A
authors: Masciulli
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Orietta
authors: O
authors: Spinelli
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Elena
authors: E
authors: Oldani
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Manuela
authors: M
authors: Tosi
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Anna
authors: A
authors: Grassi
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Margherita
authors: M
authors: Parolini
authors: Hematology Department, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Ernesta
authors: E
authors: Audisio
authors: Hematology, Spedali Civili di Brescia, Brescia, Italy.
authors: Chiara
authors: C
authors: Cattaneo
authors: Hematology and BMT Unit, Ospedale San Bortolo, Vicenza, Italy.
authors: Roberto
authors: R
authors: Raimondi
authors: Ematologia e Centro Trapianti, Ospedale Oncologico di Riferimento Regionale "Armando Businco", Azienda Ospedaliera "Brotzu", Cagliari, Italy.
authors: Emanuele
authors: E
authors: Angelucci
authors: Hematology and BMT Unit, Central Hospital of Bolzano, Bolzano, Italy.
authors: Irene Maria
authors: IM
authors: Cavattoni
authors: Hematology, Ospedale dell'Angelo & Ospedale SS, Giovanni e Paolo, Mestre-Venezia, Italy.
authors: Anna Maria
authors: AM
authors: Scattolin
authors: Oncohematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors: Agostino
authors: A
authors: Cortelezzi
authors: Hematology Department, AOU Careggi, University of Florence, Firenze, Italy.
authors: Francesco
authors: F
authors: Mannelli
authors: Hematology and Bone Marrow Transplantation Unit, San Raffaele Hospital Scientific Institute, Milan, Italy.
authors: Fabio
authors: F
authors: Ciceri
authors: Department of Hematology, Ospedale S. Croce, Cuneo, Italy.
authors: Daniele
authors: D
authors: Mattei
authors: Hematology, Spedali Civili di Brescia, Brescia, Italy.
authors: Erika
authors: E
authors: Borlenghi
authors: Hematology Division and BMT Unit, Ospedale San Gerardo, Monza, Italy.
authors: Elisabetta
authors: E
authors: Terruzzi
authors: Ematologia e Centro Trapianti, Ospedale Oncologico di Riferimento Regionale "Armando Businco", Azienda Ospedaliera "Brotzu", Cagliari, Italy.
authors: Claudio
authors: C
authors: Romani
authors: Hematology, Ospedale dell'Angelo & Ospedale SS, Giovanni e Paolo, Mestre-Venezia, Italy.
authors: Renato
authors: R
authors: Bassan
authors: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; Università degli Studi di Milano, Milano, Italy.
authors: Alessandro
authors: A
authors: Rambaldi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis*; D010677:Philadelphia Chromosome; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D055502:Secondary Prevention; D016019:Survival Analysis; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000068877:Imatinib Mesylate
keywords: Acute lymphoblastic leukemia; Allogeneic transplantation; Minimal residual disease (MRD)