title: Intermediate dose of imatinib in combination with chemotherapy followed by allogeneic stem cell transplantation improves early outcome in paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL): results of the Spanish Cooperative Group SHOP studies ALL-94, ALL-99 and ALL-2005.
abstract: Philadelphia-chromosome acute lymphoblastic leukaemia (Ph+ ALL) is a subgroup of ALL with very high risk of treatment failure. We report here the results of the Sociedad Española de Hematología y Oncología Pediátricas (SEHOP/SHOP) in paediatric Ph+ ALL treated with intermediate-dose imatinib concurrent with intensive chemotherapy. The toxicities and outcome of these patients were compared with historical controls not receiving imatinib. Patients with Ph+ ALL aged 1-18years were enrolled in three consecutive ALL/SHOP trials (SHOP-94/SHOP-99/SHOP-2005). In the SHOP-2005 trial, imatinib (260mg/m(2) per day) was given on day-15 of induction. Allogeneic haematopoietic stem-cell transplantation (HSCT) from a matched related or unrelated donor was scheduled in first complete remission (CR1). Forty-three patients were evaluable (22 boys, median age 6·8years, range, 1·2-15). Sixteen received imatinib whereas 27 received similar chemotherapy without imatinib. Seventeen of 27 and 15 of 16 patients in the non-imatinib and imatinib cohort, respectively, underwent HSCT in CR1. With a median follow-up of 109 and 39months for the non-imatinib and imatinib cohorts, the 3-year event-free survival (EFS) was 29·6% and 78·7%, respectively (P=0·01). These results show that, compared to historical controls, intermediate dose of imatinib given concomitantly with chemotherapy and followed by allogeneic HSCT markedly improved early EFS in paediatric Ph+ ALL.
authors.affiliation: Paediatric Haematology Department, Hospital Sant Joan de Déu de Barcelona Universitat de Barcelona, Barcelona, Spain. srives@hsjdbcn.org
authors.forename: Susana
authors.initials: S
authors.lastname: Rives
authors.forename: Jesús
authors.initials: J
authors.lastname: Estella
authors.forename: Pedro
authors.initials: P
authors.lastname: Gómez
authors.forename: Mónica
authors.initials: M
authors.lastname: López-Duarte
authors.forename: Purificación García
authors.initials: PG
authors.lastname: de Miguel
authors.forename: Amparo
authors.initials: A
authors.lastname: Verdeguer
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Moreno
authors.forename: José Luis
authors.initials: JL
authors.lastname: Vivanco
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Couselo
authors.forename: Rafael
authors.initials: R
authors.lastname: Fernández-Delgado
authors.forename: Marisol
authors.initials: M
authors.lastname: Maldonado
authors.forename: María
authors.initials: M
authors.lastname: Tasso
authors.forename: Blanca
authors.initials: B
authors.lastname: López-Ibor
authors.forename: Francisco
authors.initials: F
authors.lastname: Lendínez
authors.forename: Ricardo
authors.initials: R
authors.lastname: López-Almaraz
authors.forename: Javier
authors.initials: J
authors.lastname: Uriz
authors.forename: Montserrat
authors.initials: M
authors.lastname: Melo
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Teijeiro
authors.forename: Isidoro
authors.initials: I
authors.lastname: Rodríguez
authors.forename: Isabel
authors.initials: I
authors.lastname: Badell
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001549:Benzamides; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D007223:Infant; D008297:Male; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage* / Q000633:toxicity; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000633:toxicity; D013030:Spain; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate