Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia--results of the prospective multicenter LALA-94 trial.
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 High leukocyte count and m-bcr subtype were the 2 identified bad-prognosis factors for CR at 3 months, both superseded by a poor early response assessed at day 8 of the induction course.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.
Dombret
Hervé
H
Department of Hematology, Hôpital Saint-Louis, Paris, France. herve.dombret@sis.ap-hop-paris.fr
Gabert
Jean
J
Boiron
Jean-Michel
JM
Rigal-Huguet
Françoise
F
Blaise
Didier
D
Thomas
Xavier
X
Delannoy
André
A
Buzyn
Agnès
A
Bilhou-Nabera
Chrystèle
C
Cayuela
Jean-Michel
JM
Fenaux
Pierre
P
Bourhis
Jean-Henri
JH
Fegueux
Nathalie
N
Charrin
Christiane
C
Boucheix
Claude
C
Lhéritier
Véronique
V
Espérou
Hélène
H
MacIntyre
Elizabeth
E
Vernant
Jean-Paul
JP
Fière
Denis
D
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
D003561:Cytarabine; D008942:Mitoxantrone; D016044:Fusion Proteins, bcr-abl