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Dasatinib-induced complete molecular response after allogeneic hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to prior imatinib-containing regimen: a case report and discussion

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Abstract

Presence of the Philadelphia chromosome in acute lymphoblastic leukemia is the single most adverse prognostic marker associated with high risk of disease relapse and poor prognosis. Allogeneic haematopoietic stem cell transplantation is considered as the only curative option in adults with Philadelphia-positive acute lymphoblastic leukemia, but relapse remains the main cause of treatment failure. Moreover, long-term survival rates are markedly decreased when transplanted patients are not in complete remission. Incorporation of tyrosine kinase inhibitors into transplantation strategy in patients with Philadelphia-positive acute lymphoblastic leukemia may improve prognosis of the disease. Imatinib combined with conventional chemotherapy and used in conjunction with allogeneic hematopoietic stem cell transplantation has improved long-term survival rates. The more potent multikinase inhibitor dasatinib has shown enhanced activity in Philadelphia-positive acute lymphoblastic leukemia and has been approved for the treatment of adults with resistance or intolerance to prior imatinib therapy. Here, we present a case of Philadelphia-positive acute lymphoblastic leukemia primary resistant to imatinib combined with chemotherapy. Subsequently, the patient underwent allogeneic hematopoietic stem cell transplantation as a salvage therapy. Clinical evaluation performed thereafter revealed complete hematologic remission, but with the presence of the minimal residual disease detected at molecular level. Due to imatinib resistance, the therapy with dasatinib was started and complete molecular response was obtained. The consecutive clinical evaluation performed every 3 months during the last 18 months confirmed the absence of molecular minimal residual disease. We believe that inclusion of dasatinib into transplantation strategy allows obtaining sustained molecular remission even in patients resistant to imatinib.

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References

  1. Ottmann OG, et al. A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood. 2002;100:1965–71.

    Article  CAS  PubMed  Google Scholar 

  2. Ravandi F, et al. Phase II study of combination of the hyperCVAD regimen with dasatinib in patients (pts) with newly diagnosed Philadelphia chromosome positive (Ph +) acute lymphoblastic leukemia (ALL). J Clin Oncol. 2008;26:7020. abstr.

    Google Scholar 

  3. Wassmann B, et al. Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL). Blood. 2006;108:1469–77.

    Article  CAS  PubMed  Google Scholar 

  4. Yanada M, 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.

    Article  CAS  PubMed  Google Scholar 

  5. Thomas DA, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004;103:4396–407.

    Article  CAS  PubMed  Google Scholar 

  6. de Labarthe A, 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. 2007;109:1408–13.

    Article  PubMed  CAS  Google Scholar 

  7. Ottmann O, 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.

    Article  CAS  PubMed  Google Scholar 

  8. Radich J, et al. Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation. Blood. 1997;89:2602–9.

    CAS  PubMed  Google Scholar 

  9. Stirewalt DL, et al. Predictors of relapse and overall survival in Philadelphia chromosome-positive acute lymphoblastic leukemia after transplantation. Biol Blood Marrow Transpl. 2003;9:206–12.

    Article  Google Scholar 

  10. Wassmann B, et al. Early molecular response to posttransplantation imatinib determines outcome in MRD + Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL). Blood. 2005;106:458–63.

    Article  CAS  PubMed  Google Scholar 

  11. Carpenter PA, et al. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood. 2007;109:2791–3.

    CAS  PubMed  Google Scholar 

  12. Holowiecki J, et al. Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The polish adult Leukemia group ALL 4–2002 MRD study. Br J Haematol. 2008;142:227–37.

    Article  PubMed  Google Scholar 

  13. Giebel S, et al. Fludarabine, cytarabine, and mitoxantrone (FLAM) for the treatment of relapsed and refractory adult acute lymphoblastic leukemia. A phase study by the polish adult leukemia group (PALG). Ann Hematol. 2006;85:717–22.

    Article  CAS  PubMed  Google Scholar 

  14. Lucio P, et al. Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. Leukemia. 1999;13:419–27.

    Article  CAS  PubMed  Google Scholar 

  15. Preudhomme C, et al. Good correlation between RT-PCR analysis and relapse in Philadelphia (Ph1)-positive acute lymphoblastic leukemia (ALL). Leukemia. 1997;11:294–8.

    Article  CAS  PubMed  Google Scholar 

  16. Dombret H, et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia—results of the prospective multicenter LALA-94 trial. Blood. 2002;100:2357–66.

    Article  CAS  PubMed  Google Scholar 

  17. Pane F, et al. Significant reduction of the hybrid BCR/ABL transcripts after induction and consolidation therapy is a powerful predictor of treatment response in adult Philadelphia-positive acute lymphoblastic leukemia. Leukemia. 2005;19:628–35.

    CAS  PubMed  Google Scholar 

  18. Lee S, et al. The extent of minimal residual disease reduction after the first 4-week imatinib therapy determines outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer. 2009;115:561–70.

    Article  CAS  PubMed  Google Scholar 

  19. Ottmann OG, Pfeifer H. First-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia in adults. Curr Opin Oncol. 2009;21(Suppl 1):S43–6.

    Article  CAS  PubMed  Google Scholar 

  20. Quintas-Cardama A, Cortes J. Dasatinib-induced restoration of donor chimerism in BCR-ABL1-positive ALL after failure of imatinib therapy and allo-SCT. Bone Marrow Transpl. 2009;43:579–81.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Poznan University of Medical Sciences, Szamarzewskiego 84 Str., 60-569, Poznan, Poland

    Anna Czyz, Krzysztof Lewandowski, Renata Kroll & Mieczysław Komarnicki

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  1. Anna Czyz
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  2. Krzysztof Lewandowski
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  3. Renata Kroll
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  4. Mieczysław Komarnicki
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Correspondence to Anna Czyz.

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Czyz, A., Lewandowski, K., Kroll, R. et al. Dasatinib-induced complete molecular response after allogeneic hematopoietic stem cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to prior imatinib-containing regimen: a case report and discussion. Med Oncol 27, 1123–1126 (2010). https://doi.org/10.1007/s12032-009-9347-0

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  • DOI: https://doi.org/10.1007/s12032-009-9347-0

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