Published online 1 October 2009
(Haematologica 2009, 10.3324/haematol.2009.011221)
Copyright © 2009 by Ferrata Storti Foundation
Josep-Maria Ribera1 ,
Albert Oriol1 ,
Marcos González2 ,
Belén Vidriales2 ,
Salut Brunet3 ,
Jordi Esteve4 ,
Eloy del Potro4 ,
Concepción Rivas6 ,
Maria-José Moreno7 ,
Mar Tormo8 ,
Victoria Martín-Reina9 ,
Josep Sarrá10 ,
Ricardo Parody11 ,
Jaime Pérez de Oteyza12 ,
Encarna Bureo13 ,
Maria-Teresa Bernal on behalf of the Programa Español de Tratamiento en Hematología (PETHEMA) and Grupo Español de Trasplante Hemopoyético (GETH) Groups
(Haematologica 2009, 10.3324/haematol.2009.011221)
Copyright © 2009 by Ferrata Storti Foundation
Original Article |
Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial
1 Departments of Hematology of the Hospitals Institut Català d’Oncologia-Hospital Germans Trias i Pujol, Badalona
2 Clínico, Salamanca
3 Sant Pau, Barcelona
4 Clínic, Barcelona
5 Clínico San Carlos, Madrid
6 Universitario, Alicante
7 Clínico Virgen de la Victoria, Málaga
8 Clínico, Valencia
9 Puerta del Mar, Cádiz
10 Duran y Reynals, Barcelona
11 Virgen del Rocío, Sevilla
12 Ramón y Cajal, Madrid
13 Marqués de Valdecilla, Santander, and Central de Asturias (EMR), Spain
Correspondence: Josep-Maria Ribera, Department of Hematology of the Hospitals Institut Català d’Oncologia-Hospital Germans Trias i Pujol, Badalona. E-mail:jribera{at}iconcologia.net
ABSTRACT
Background: Several studies have shown that imatinib, concurrent or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) but relapses are still frequent. The objective of this study was to evaluate the feasibility and results of a therapy program with imatinib concurrent with intensive chemotherapy, stem cell transplantation (SCT) and imatinib after SCT for newly diagnosed Ph+ ALL patients.
Design and Methods: Phase II study including patients with newly diagnosed Ph+ ALL in whom standard chemotherapy, together with imatinib (400 mg/d), was given up to SCT and imatinib was scheduled in all patients after SCT regardless of the molecular status of the disease.
Results: Of the 30 patients included 27 (90%) achieved complete remission (CR), one was resistant and two died during induction therapy . The percentages of major and complete molecular response were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease (MRD) in parallel by multiparametric flow cytometry.SCT was performed in 21 out of the 27 CR patients (including 16 allogeneic). Imatinib could be administered at a dose of 400 mg/d after SCT for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients, being due to side effects of the drug in 2 patients. Nine patients relapsed, 4 before and 5 after SCT and 8 patients had non-relapse transplant-related death. With a median follow-up of 4.1 years, the probabilities (95%CI) of disease-free and overall survival were 30% (15% to 45%) and 30 % (16% to 45%), respectively.
Conclusions: These results confirm that imatinib is an effective first-line treatment for adult Ph+ ALL when given concurrently with chemotherapy, making SCT feasible in a high proportion of patients. However, imatinib administration after SCT was limited mainly because of SCT-derived complications rather than drug-specific toxicity.
Key words: acute lymphoblastic leukemia, Philadelphia chromosome, BCR-ABL, imatinib, intensive chemotherapy, stem cell transplantation, imatinib maintenance.
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