title: The combination of bortezomib with chemotherapy to treat relapsed/refractory acute lymphoblastic leukaemia of childhood.
abstract: Achieving complete remission (CR) in childhood relapsed/refractory acute lymphoblastic leukaemia (ALL) is a difficult task. Bortezomib, a proteasome inhibitor, has in vitro activity against ALL blasts. A phase I-II trial, reported by the Therapeutic Advances in Childhood Leukaemia and Lymphoma (TACL) consortium, demonstrated that bortezomib with chemotherapy has acceptable toxicity and remarkable activity in patients with relapsed ALL failing 2-3 previous regimens. We evaluated bortezomib in combination with chemotherapy in 30 and 7 children with B-cell precursor (BCP) and T-cell ALL, respectively. Bortezomib (1·3 mg/m2/dose) was administered intravenously on days 1, 4, 8, and 11. Chemotherapy agents were the same as those used in the TACL trial, consisting of dexamethasone, doxorubicin, vincristine and pegylated asparaginase. Three patients (8·1%) died due to infections. Twenty-seven patients (72·9%) achieved CR or CR with incomplete platelet recovery (CRp). Fourteen had minimal residual disease (MRD) lower than 0·1%. Twenty-two of 30 BCP-ALL patients (73·3%) and 5/7 patients (71%) with T-cell ALL achieved CR/CRp. The 2-year overall survival (OS) is 31·3%; CR/CRp patients with an MRD response had a remarkable 2-year OS of 68·4%. These data confirm that the combination of bortezomib with chemotherapy is a suitable/effective option for childhood relapsed/refractory ALL.
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Vinti
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Strocchio
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gaspari
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Caruso
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Algeri
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Coletti
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Gurnari
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Romano
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Cefalo
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Girardi
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Trevisan
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bertaina
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Merli
authors.affiliation: Department of Paediatric Haematology-Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.|Department of Paediatrics, University of Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase; D000069286:Bortezomib / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone; D004317:Doxorubicin; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D011092:Polyethylene Glycols; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D061988:Proteasome Inhibitors; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis; D014750:Vincristine; D055815:Young Adult
chemical_list: D061988:Proteasome Inhibitors; D011092:Polyethylene Glycols; D014750:Vincristine; D000069286:Bortezomib; C042705:pegaspargase; D003907:Dexamethasone; D004317:Doxorubicin; D001215:Asparaginase
keywords: acute lymphoblastic leukaemia; bortezomib; childhood leukaemia; minimal residual disease; relapsed/refractory disease