Skip to main content
Top
Published in: International Journal of Hematology 3/2010

01-10-2010 | Case Report

Dasatinib followed by second allogeneic hematopoietic stem cell transplantation for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia after the first transplantation

Authors: Yoko Ishida, Kiriko Terasako, Kumi Oshima, Kana Sakamoto, Masahiro Ashizawa, Miki Sato, Misato Kikuchi, Shun-ichi Kimura, Hideki Nakasone, Shinya Okuda, Shinichi Kako, Rie Yamazaki, Junji Nishida, Yoshinobu Kanda

Published in: International Journal of Hematology | Issue 3/2010

Login to get access

Abstract

Although allogeneic hematopoietic stem cell transplantation (HSCT) is an established treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL), the prognosis of patients who relapse after allogeneic HSCT has been extremely poor. Dasatinib, a second-generation tyrosine kinase inhibitor, is a promising agent for the treatment of Ph-ALL. We report on a Ph-ALL patient who relapsed early after the first allogeneic HSCT, but achieved complete molecular remission with dasatinib alone. She remains in molecular remission 12 months after the second allogeneic HSCT. Dasatinib was generally well tolerated, but she developed myalgia, nausea and positive cytomegalovirus antigenemia. In addition, sudden-onset bloody diarrhea was observed 10 days after the second HSCT, which was possibly associated with the use of dasatinib in addition to the effect of the conditioning regimen and graft-versus-host disease. In conclusion, dasatinib is an effective agent for Ph-ALL with a poor prognosis, but may be associated with specific adverse events including opportunistic infection and gastrointestinal bleeding.
Literature
1.
go back to reference Ottmann OG, Pfeifer H. Management of Philadelphia chromosome-positive acute lymphoblastic leukemia (ph+ all). Hematol Am Soc Hematol Educ Program. 2009;371–81. Ottmann OG, Pfeifer H. Management of Philadelphia chromosome-positive acute lymphoblastic leukemia (ph+ all). Hematol Am Soc Hematol Educ Program. 2009;371–81.
2.
go back to reference Yanada M, Naoe T, Iida H, Sakamaki H, Sakura T, Kanamori H, et al. Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease. Bone Marrow Transplant. 2005;36:867–72.CrossRefPubMed Yanada M, Naoe T, Iida H, Sakamaki H, Sakura T, Kanamori H, et al. Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease. Bone Marrow Transplant. 2005;36:867–72.CrossRefPubMed
3.
go back to reference Khoury HJ, Guilhot F, Hughes TP, Kim DW, Cortes JE. Dasatinib treatment for Philadelphia chromosome-positive leukemias: practical considerations. Cancer. 2009;115:1381–94.CrossRefPubMed Khoury HJ, Guilhot F, Hughes TP, Kim DW, Cortes JE. Dasatinib treatment for Philadelphia chromosome-positive leukemias: practical considerations. Cancer. 2009;115:1381–94.CrossRefPubMed
4.
go back to reference Ottmann O, Dombret H, Martinelli G, Simonsson B, Guilhot F, Larson RA, 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;110:2309–15.CrossRefPubMed Ottmann O, Dombret H, Martinelli G, Simonsson B, Guilhot F, Larson RA, 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;110:2309–15.CrossRefPubMed
5.
go back to reference Yanada M, Takeuchi J, Sugiura I, Akiyama H, Usui N, Yagasaki F, et al. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR–ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol. 2006;24:460–6.CrossRefPubMed Yanada M, Takeuchi J, Sugiura I, Akiyama H, Usui N, Yagasaki F, et al. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR–ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol. 2006;24:460–6.CrossRefPubMed
6.
go back to reference Oshima K, Kanda Y, Nakasone H, Arai S, Nishimoto N, Sato H, et al. Decreased incidence of acute graft-versus-host disease by continuous infusion of cyclosporine with a higher target blood level. Am J Hematol. 2008;83:226–32.CrossRefPubMed Oshima K, Kanda Y, Nakasone H, Arai S, Nishimoto N, Sato H, et al. Decreased incidence of acute graft-versus-host disease by continuous infusion of cyclosporine with a higher target blood level. Am J Hematol. 2008;83:226–32.CrossRefPubMed
7.
go back to reference Kanda Y, Mineishi S, Saito T, Saito A, Ohnishi M, Niiya H, et al. Response-oriented preemptive therapy against cytomegalovirus disease with low-dose ganciclovir: a prospective evaluation. Transplantation. 2002;73:568–72.CrossRefPubMed Kanda Y, Mineishi S, Saito T, Saito A, Ohnishi M, Niiya H, et al. Response-oriented preemptive therapy against cytomegalovirus disease with low-dose ganciclovir: a prospective evaluation. Transplantation. 2002;73:568–72.CrossRefPubMed
8.
go back to reference Fei F, Yu Y, Schmitt A, Rojewski MT, Chen B, Greiner J, et al. Dasatinib exerts an immunosuppressive effect on CD8+ T cells specific for viral and leukemia antigens. Exp Hematol. 2008;36:1297–308.CrossRefPubMed Fei F, Yu Y, Schmitt A, Rojewski MT, Chen B, Greiner J, et al. Dasatinib exerts an immunosuppressive effect on CD8+ T cells specific for viral and leukemia antigens. Exp Hematol. 2008;36:1297–308.CrossRefPubMed
9.
go back to reference Jabbour E, Cortes J, Kantarjian H, Giralt S, Andersson BS, Giles F, et al. Novel tyrosine kinase inhibitor therapy before allogeneic stem cell transplantation in patients with chronic myeloid leukemia: no evidence for increased transplant-related toxicity. Cancer. 2007;110:340–4.CrossRefPubMed Jabbour E, Cortes J, Kantarjian H, Giralt S, Andersson BS, Giles F, et al. Novel tyrosine kinase inhibitor therapy before allogeneic stem cell transplantation in patients with chronic myeloid leukemia: no evidence for increased transplant-related toxicity. Cancer. 2007;110:340–4.CrossRefPubMed
10.
go back to reference Breccia M, Palandri F, Iori AP, Colaci E, Latagliata R, Castagnetti F, et al. Second-generation tyrosine kinase inhibitors before allogeneic stem cell transplantation in patients with chronic myeloid leukemia resistant to imatinib. Leuk Res. 2010;34:143–7.CrossRefPubMed Breccia M, Palandri F, Iori AP, Colaci E, Latagliata R, Castagnetti F, et al. Second-generation tyrosine kinase inhibitors before allogeneic stem cell transplantation in patients with chronic myeloid leukemia resistant to imatinib. Leuk Res. 2010;34:143–7.CrossRefPubMed
11.
go back to reference Shimoni A, Leiba M, Schleuning M, Martineau G, Renaud M, Koren-Michowitz M, et al. Prior treatment with the tyrosine kinase inhibitors dasatinib and nilotinib allows stem cell transplantation (SCT) in a less advanced disease phase and does not increase SCT toxicity in patients with chronic myelogenous leukemia and Philadelphia positive acute lymphoblastic leukemia. Leukemia. 2009;23:190–4.CrossRefPubMed Shimoni A, Leiba M, Schleuning M, Martineau G, Renaud M, Koren-Michowitz M, et al. Prior treatment with the tyrosine kinase inhibitors dasatinib and nilotinib allows stem cell transplantation (SCT) in a less advanced disease phase and does not increase SCT toxicity in patients with chronic myelogenous leukemia and Philadelphia positive acute lymphoblastic leukemia. Leukemia. 2009;23:190–4.CrossRefPubMed
12.
go back to reference Quintas-Cardama A, Kantarjian H, Ravandi F, O’Brien S, Thomas D, Vidal-Senmache G, et al. Bleeding diathesis in patients with chronic myelogenous leukemia receiving dasatinib therapy. Cancer. 2009;115:2482–90.CrossRefPubMed Quintas-Cardama A, Kantarjian H, Ravandi F, O’Brien S, Thomas D, Vidal-Senmache G, et al. Bleeding diathesis in patients with chronic myelogenous leukemia receiving dasatinib therapy. Cancer. 2009;115:2482–90.CrossRefPubMed
13.
go back to reference Ravandi F, O’Brien S, Thomas D, Faderl S, Jones D, Garris R, et al.: First report of phase II study of dasatinib with hyperCVAD for the frontline treatment of patients with Philadelphia chromosome positive (ph+) acute lymphoblastic leukemia. Blood (in press). Ravandi F, O’Brien S, Thomas D, Faderl S, Jones D, Garris R, et al.: First report of phase II study of dasatinib with hyperCVAD for the frontline treatment of patients with Philadelphia chromosome positive (ph+) acute lymphoblastic leukemia. Blood (in press).
14.
go back to reference Quintas-Cardama A, Han X, Kantarjian H, Cortes J. Tyrosine kinase inhibitor-induced platelet dysfunction in patients with chronic myeloid leukemia. Blood. 2009;114:261–3.CrossRefPubMed Quintas-Cardama A, Han X, Kantarjian H, Cortes J. Tyrosine kinase inhibitor-induced platelet dysfunction in patients with chronic myeloid leukemia. Blood. 2009;114:261–3.CrossRefPubMed
15.
go back to reference Christopher LJ, Cui D, Wu C, Luo R, Manning JA, Bonacorsi SJ, et al. Metabolism and disposition of dasatinib after oral administration to humans. Drug Metab Dispos. 2008;36:1357–64.CrossRefPubMed Christopher LJ, Cui D, Wu C, Luo R, Manning JA, Bonacorsi SJ, et al. Metabolism and disposition of dasatinib after oral administration to humans. Drug Metab Dispos. 2008;36:1357–64.CrossRefPubMed
16.
go back to reference Mustjoki S, Ekblom M, Arstila TP, Dybedal I, Epling-Burnette PK, Guilhot F, et al. Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia. 2009;23:1398–405.CrossRefPubMed Mustjoki S, Ekblom M, Arstila TP, Dybedal I, Epling-Burnette PK, Guilhot F, et al. Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy. Leukemia. 2009;23:1398–405.CrossRefPubMed
Metadata
Title
Dasatinib followed by second allogeneic hematopoietic stem cell transplantation for relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia after the first transplantation
Authors
Yoko Ishida
Kiriko Terasako
Kumi Oshima
Kana Sakamoto
Masahiro Ashizawa
Miki Sato
Misato Kikuchi
Shun-ichi Kimura
Hideki Nakasone
Shinya Okuda
Shinichi Kako
Rie Yamazaki
Junji Nishida
Yoshinobu Kanda
Publication date
01-10-2010
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 3/2010
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-010-0678-6

Other articles of this Issue 3/2010

International Journal of Hematology 3/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine