|
|
Blood, 1 September 2006, Vol. 108, No. 5, pp. 1469-1477.
Prepublished online as a Blood First Edition Paper on April 25, 2006; DOI 10.1182/blood-2005-11-4386.
 Previous Article | Table of Contents | Next Article 
CLINICAL TRIALS AND OBSERVATIONS
Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL)
Barbara Wassmann,
Heike Pfeifer,
Nicola Goekbuget,
Dietrich W. Beelen,
Joachim Beck,
Matthias Stelljes,
Martin Bornhäuser,
Albrecht Reichle,
Jolanta Perz,
Rainer Haas,
Arnold Ganser,
Mathias Schmid,
Lothar Kanz,
Georg Lenz,
Martin Kaufmann,
Anja Binckebanck,
Patrick Brück,
Regina Reutzel,
Harald Gschaidmeier,
Stefan Schwartz,
Dieter Hoelzer, and
Oliver G. Ottmann
From the Departments of Hematology and Oncology of the Johann Wolfgang Goethe University, Frankfurt; the University of Essen; the University of Mainz; the University of Münster; the University of Dresden; the University of Regensburg; the University of Heidelberg; the University of Düsseldorf; the University of Hannover; the University of Ulm; the University of Tübingen; the Ludwig Maximilans University, Munich; the Robert Bosch Krankenhaus, Stuttgart; Novartis Pharma, Nuremberg; and Charité, Campus Benjamin Franklin, Berlin, Germany.
The best strategy for incorporating imatinib in front-line treatment of Ph+ acute lymphoblastic leukemia (ALL) has not been established. We enrolled 92 patients with newly diagnosed Ph+ALL in a prospective, multicenter study to investigate sequentially 2 treatment schedules with imatinib administered concurrent to or alternating with a uniform induction and consolidation regimen. Coadministration of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR) rate of 95% and polymerase chain reaction (PCR) negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (P = .01). Remarkably, patients with and without a CR after induction cycle 1 (INDI) had similar hematologic and molecular responses after concurrent imatinib and INDII. In the concurrent cohort, grades III and IV cytopenias and transient hepatotoxicity necessitated interruption of induction in 87% and 53% of patients, respectively; however, duration of induction was not prolonged when compared with patients receiving chemotherapy alone. No imatinib-related severe hematologic or nonhematologic toxicities were noted with the alternating schedule. In each cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in first CR (CR1). Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic efficacy.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Yanada, J. Takeuchi, I. Sugiura, H. Akiyama, N. Usui, F. Yagasaki, K. Nishii, Y. Ueda, M. Takeuchi, S. Miyawaki, et al.
Karyotype at diagnosis is the major prognostic factor predicting relapse-free survival for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib-combined chemotherapy
Haematologica,
February 1, 2008;
93(2):
287 - 290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Wetzler
Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia: On Target to Improve Outcome
ASCO Educational Book,
January 1, 2008;
2008(1):
275 - 279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J.L. Kaspers and C. M. Zwaan
Pediatric acute myeloid leukemia: towards high-quality cure of all patients
Haematologica,
November 1, 2007;
92(11):
1519 - 1532.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Ottmann, H. Dombret, G. Martinelli, B. Simonsson, F. Guilhot, R. A. Larson, G. Rege-Cambrin, J. Radich, A. Hochhaus, A. M. Apanovitch, et al.
Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study
Blood,
October 1, 2007;
110(7):
2309 - 2315.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Pfeifer, B. Wassmann, A. Pavlova, L. Wunderle, J. Oldenburg, A. Binckebanck, T. Lange, A. Hochhaus, S. Wystub, P. Bruck, et al.
Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)
Blood,
July 15, 2007;
110(2):
727 - 734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Spinelli, B. Peruta, M. Tosi, V. Guerini, A. Salvi, M. C. Zanotti, E. Oldani, A. Grassi, T. Intermesoli, C. Mico, et al.
Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia
Haematologica,
May 1, 2007;
92(5):
612 - 618.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Carpenter, D. S. Snyder, M. E. D. Flowers, J. E. Sanders, T. A. Gooley, P. J. Martin, F. R. Appelbaum, and J. P. Radich
Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia
Blood,
April 1, 2007;
109(7):
2791 - 2793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. de Labarthe, P. Rousselot, F. Huguet-Rigal, E. Delabesse, F. Witz, S. Maury, D. Rea, J.-M. Cayuela, M.-C. Vekemans, O. Reman, et al.
Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study
Blood,
February 15, 2007;
109(4):
1408 - 1413.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Thomas
Philadelphia Chromosome Positive Acute Lymphocytic Leukemia: A New Era of Challenges
Hematology,
January 1, 2007;
2007(1):
435 - 443.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Gokbuget and D. Hoelzer
Treatment of Adult Acute Lymphoblastic Leukemia
Hematology,
January 1, 2006;
2006(1):
133 - 141.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
