title: 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.
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.
authors.affiliation: Department of Hematology, Poznan University of Medical Sciences, Szamarzewskiego 84 Str., 60-569, Poznan, Poland. aczyz@onet.eu
authors.forename: Anna
authors.initials: A
authors.lastname: Czyz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lewandowski
authors.forename: Renata
authors.initials: R
authors.lastname: Kroll
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Komarnicki
mesh_terms: D001549:Benzamides; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000473:pathology; D010879:Piperazines / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use*; D012074:Remission Induction; D016879:Salvage Therapy; D015996:Survival Rate; D013844:Thiazoles / Q000627:therapeutic use*; D014182:Transplantation, Autologous
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib