The role of BCR/ABL isoforms in the presentation and outcome of patients with Philadelphia-positive acute lymphoblastic leukemia: a seven-year update of the GIMEMA 0496 trial.
To verify the potential clinical and prognostic value of BCR/ABL isoforms, we analyzed 101 consecutive adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia enrolled in the GIMEMA 0496 trial between October 1996 and December 1999. A p190 or p210 with or without p190 BCR/ABL transcript was documented in 59 (58.5%) and 42 cases (41.5%), respectively. At diagnosis, a white cell count <16 x 10(9)/L and a higher level of CD34 and CD33 expression were associated with the p190 BCR/ABL transcript (p<0.05, p=0.009 and p=0.03, respectively). A complete remission was achieved in 62/92 (67.4%) patients, while 16/92 (17.4%) were resistant and 14/92 (15.2%) died of therapy-related complications. Fifty-two patients underwent intensive re-induction treatment, which was followed by stem cell transplant consolidation in the 36 in persistent complete remission (allogeneic = 20 patients; autologous = 16 patients). Response rates to induction therapies were similar in the two BCR/ABL isoform groups. By contrast, the p190 emerged as the only independent prognostic factor favorably affecting the 5-year overall survival and disease-free survival rates (p=0.008 and p=0.02, respectively).
Cimino
Giuseppe
G
Division of Hematology, Dept. of Cellular Biotechnology and Hematology, University La Sapienza, Via Benevento 6, 00161 Rome, Italy. cimino@bce.uniroma1.it
Pane
Fabrizio
F
Elia
Loredana
L
Finolezzi
Erica
E
Fazi
Paola
P
Annino
Luciana
L
Meloni
Giovanna
G
Mancini
Marco
M
Tedeschi
Alessandra
A
Di Raimondo
Francesco
F
Specchia
Giorgina
G
Fioritoni
Giuseppe
G
Leoni
Pietro
P
Cuneo
Antonio
A
Mecucci
Cristina
C
Saglio
Giuseppe
G
Mandelli
Franco
F
Foà
Robin
R
D000328:Adult; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology*; D005819:Genetic Markers / Q000235:genetics / Q000502:physiology; D006801:Humans; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D005819:Genetic Markers; D020033:Protein Isoforms; D016044:Fusion Proteins, bcr-abl