Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00.
OBJECTIVE
Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates.


METHODS
Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib.


RESULTS
CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall.


CONCLUSIONS
This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure.
Bassan
Renato
R
U.S.C. Ematologia, Ospedali Riuniti, Bergamo, Italy. rbassan@ospedaliriuniti.bergamo.it
Rossi
Giuseppe
G
Pogliani
Enrico M
EM
Di Bona
Eros
E
Angelucci
Emanuele
E
Cavattoni
Irene
I
Lambertenghi-Deliliers
Giorgio
G
Mannelli
Francesco
F
Levis
Alessandro
A
Ciceri
Fabio
F
Mattei
Daniele
D
Borlenghi
Erika
E
Terruzzi
Elisabetta
E
Borghero
Carlo
C
Romani
Claudio
C
Spinelli
Orietta
O
Tosi
Manuela
M
Oldani
Elena
E
Intermesoli
Tamara
T
Rambaldi
Alessandro
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007558:Italy; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage*; D012074:Remission Induction; D033581:Stem Cell Transplantation
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate