title: Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia--results of the prospective multicenter LALA-94 trial.
abstract: From 1994 to 2000, 154 adults with Philadelphia chromosome-positive (Ph(+)) and/or BCR-ABL(+) acute lymphoblastic leukemia (ALL) were treated according to a prospective trial (median follow-up, 4.5 years) with the aim to study the prognostic value of early response to therapy and the role of stem cell transplantation (SCT) in first complete remission (CR). All patients received a standard induction course followed by a course of mitoxantrone and intermediate-dose cytarabine (HAM). After each course, minimal residual disease was tested by specific reverse transcriptase-polymerase chain reaction (RT-PCR) (median sensitivity, 10(-5)). Allogeneic SCT (if a donor) or autologous SCT (if not) was planned at 3 months in all patients in CR after HAM. CR rates after induction, after HAM, and at 3 months were 53%, 67%, and 62%, respectively. High leukocyte count and m-bcr subtype were the 2 identified bad-prognosis factors for CR at 3 months, both superseded by a poor early response assessed at day 8 of the induction course. HAM-associated salvage rate was higher in patients with M-bcr than in those with m-bcr ALL (55% vs 30%; P =.05). In the 103 patients eligible for SCT, the existence of a donor and the negative BCR-ABL status after HAM were independently predictive of remission duration (P <.001 and.01, respectively) and survival (P =.02 and.01, respectively). Relapse was the most common cause of treatment failure in all patient groups. Allogeneic SCT in first CR is the current best treatment option in adults with the disease. New strategies must be tested during early phases of therapy to increase the rate of BCR-ABL(-) remissions.
authors.affiliation: Department of Hematology, Hôpital Saint-Louis, Paris, France. herve.dombret@sis.ap-hop-paris.fr
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.forename: Jean
authors.initials: J
authors.lastname: Gabert
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Boiron
authors.forename: Françoise
authors.initials: F
authors.lastname: Rigal-Huguet
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: André
authors.initials: A
authors.lastname: Delannoy
authors.forename: Agnès
authors.initials: A
authors.lastname: Buzyn
authors.forename: Chrystèle
authors.initials: C
authors.lastname: Bilhou-Nabera
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Jean-Henri
authors.initials: JH
authors.lastname: Bourhis
authors.forename: Nathalie
authors.initials: N
authors.lastname: Fegueux
authors.forename: Christiane
authors.initials: C
authors.lastname: Charrin
authors.forename: Claude
authors.initials: C
authors.lastname: Boucheix
authors.forename: Véronique
authors.initials: V
authors.lastname: Lhéritier
authors.forename: Hélène
authors.initials: H
authors.lastname: Espérou
authors.forename: Elizabeth
authors.initials: E
authors.lastname: MacIntyre
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
authors.forename: Denis
authors.initials: D
authors.lastname: Fière
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000032:analysis; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D018365:Neoplasm, Residual / Q000628:therapy*; D018579:Patient Selection; D011003:Ploidies; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone; D016044:Fusion Proteins, bcr-abl