title: Second-generation tyrosine kinase inhibitors before allogeneic stem cell transplantation in patients with chronic myeloid leukemia resistant to imatinib.
abstract: Philadelphia-positive chronic myeloid leukemia (Ph+ CML) patients who are resistant to imatinib are commonly treated with second-generation tyrosine kinase inhibitors (TKIs). Limited data exist on the possible effects of these drugs on subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT).The outcome of 12 imatinib-resistant CML patients treated with dasatinib or nilotinib or both before allo-HSCT, was retrospectively analyzed. Patients were treated with second-generation TKIs for 1-17 months (median, 8). At the time of transplant, 3 patients were in complete cytogenetic response (CCgR), 3 patients in partial cytogenetic response (PCgR) and 6 patients were in less than PCgR. Donors were HLA-matched related in 4 cases and unrelated in 8 cases. Stem cell source was peripheral blood, bone marrow or cord blood in 6, 5 and 1 cases, respectively. All patients engrafted successfully and all but one achieved a full donor chimerism. Three patients experienced acute and chronic graft-versus-host disease. No cases of transplant-related mortality were recorded. Best response to allo-HSCT was complete molecular response (CMR) in 9 patients, major molecular response (MMR) in 1 patient and CCgR in 2 patients. Median follow-up was 16.5 months. At the last evaluation, 9 patients were in continuous CMR and 1 patient was in MMR; 2 patients had died of disease progression. Second-generation TKIs given before allo-HSCT do not negatively affect transplant engraftment and response rate, nor increases transplant-related toxicity.
authors.affiliation: Department of Cellular Biotechnologies and Hematology, La Sapienza University, Rome, Italy. breccia@bce.uniroma1.it
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Francesca
authors.initials: F
authors.lastname: Palandri
authors.forename: Anna Paola
authors.initials: AP
authors.lastname: Iori
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Colaci
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.forename: Fausto
authors.initials: F
authors.lastname: Castagnetti
authors.forename: Giovanni Fernando
authors.initials: GF
authors.lastname: Torelli
authors.forename: Sara
authors.initials: S
authors.lastname: Usai
authors.forename: Veronica
authors.initials: V
authors.lastname: Valle
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage*; D012074:Remission Induction / Q000379:methods; D013844:Thiazoles / Q000008:administration & dosage*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib