Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2015 Dec 1;121(23):4158-64.
doi: 10.1002/cncr.29646. Epub 2015 Aug 26.

Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Farhad Ravandi  1 , Susan M O'Brien  1 , Jorge E Cortes  1 , Deborah M Thomas  1 , Rebecca Garris  1 , Stefan Faderl  1 , Jan A Burger  1 , Michael E Rytting  1 , Alessandra Ferrajoli  1 , William G Wierda  1 , Srdan Verstovsek  1 , Richard Champlin  2 , Partow Kebriaei  2 , Deborah A McCue  3 , Xuelin Huang  4 , Elias Jabbour  1 , Guillermo Garcia-Manero  1 , Zeev Estrov  1 , Hagop M Kantarjian  1
Affiliations
Clinical Trial

Long-term follow-up of a phase 2 study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia

Farhad Ravandi et al. Cancer. .

Abstract

Background: The long-term efficacy of a combination of chemotherapy and dasatinib in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is not well established.

Methods: Patients received dasatinib with 8 cycles of alternating hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and high-dose cytarabine and methotrexate. Patients in complete remission (CR) continued maintenance dasatinib, vincristine, and prednisone for 2 years, which was followed by dasatinib indefinitely. Patients eligible for allogeneic stem cell transplantation (SCT) received it during their first CR.

Results: Seventy-two patients with a median age of 55 years (range, 21-80 years) were treated; 69 (96%) achieved CR. Among them, 57 (83%) achieved cytogenetic CR after 1 cycle, and 64 (93%) achieved a major molecular response at a median of 4 weeks (range, 2-38 weeks). Sixty-five patients (94%) were negative for minimal residual disease assessed by flow cytometry at a median of 3 weeks (range, 2-37 weeks). Dasatinib-related grade 3 and 4 adverse events included bleeding, pleural/pericardial effusions, and elevated transaminases. With a median follow-up of 67 months (range, 33-97 months), 33 patients (46%) were alive, and 30 (43%) were in CR; 12 underwent allogeneic SCT. Thirty-nine patients died (3 at induction, 19 after relapse, 7 after SCT performed during first CR, and 10 during CR). The median disease-free survival and overall survival were 31 (range, 0.3-97 months) and 47 months (range, 0.2-97 months), respectively. Seven relapsed patients had BCR-ABL kinase domain mutations, including 4 with T315I.

Conclusions: A combination of chemotherapy with dasatinib is effective in achieving long-term remission for patients with newly diagnosed Ph + ALL.

Keywords: Philadelphia chromosome; acute lymphoblastic leukemia; chemotherapy; combination; dasatinib.

PubMed Disclaimer

Figures

Figure 1
Figure 1
a) Disease-free survival for all patients, b) Overall survival for all patients c) Event-free survival for all patients
Figure 1
Figure 1
a) Disease-free survival for all patients, b) Overall survival for all patients c) Event-free survival for all patients
Figure 1
Figure 1
a) Disease-free survival for all patients, b) Overall survival for all patients c) Event-free survival for all patients
Figure 2
Figure 2
(a) Survival by whether or not received allogeneic stem cell transplant in CR1; (b) Survival by whether or not received transplant in CR1 and age < and ≥ 40 years
Figure 2
Figure 2
(a) Survival by whether or not received allogeneic stem cell transplant in CR1; (b) Survival by whether or not received transplant in CR1 and age < and ≥ 40 years
Figure 3
Figure 3
Grade 3 and 4 toxicities
See this image and copyright information in PMC

References

    1. Kantarjian H, O'Brien S, Jabbour E, et al. Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience. Blood. 2012;119(9):1981–1987. - PMC - PubMed
    1. Hoelzer D. Advances in the management of Ph-positive ALL. Clin Adv Hematol Oncol. 2006;4(11):804–805. - PubMed
    1. Ottmann OG, Druker BJ, Sawyers CL, et al. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood. 2002;100(6):1965–1971. - PubMed
    1. Ottmann O, Dombret H, Martinelli G, 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. 2007;110(7):2309–2315. - PubMed
    1. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004;103(12):4396–4407. - PubMed

Publication types

MeSH terms