title: Sudden blast crisis in patients with Philadelphia chromosome-positive chronic myeloid leukemia who achieved complete cytogenetic remission after imatinib therapy.
abstract: BACKGROUND
  Most patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) in chronic phase (CP) who receive treatment with imatinib achieve complete cytogenetic remission (CCR), which is correlated tightly with long-term progression-free survival. In these patients, the occurrence of blastic crisis (BC) is rare, and its clinical biologic characteristics are not well known.
  
  
  METHODS
  Among 164 patients who received imatinib and were followed for a median of 35 months, 11 patients (6.7%) developed a BC; this was sudden (i.e., it occurred within 3 months of a documented CCR) in 6 patients (54.5%). Those patients were analyzed with respect to their clinical and biologic features and were compared with previous reports.
  
  
  RESULTS
  At the time of diagnosis, there were 3 low-risk patients and 3 intermediate-risk patients; 4 patients had received pretreatment with interferon, and 2 patients received only imatinib. The median CP was 18 months, and the median duration of imatinib therapy was 7 months. The median time to CCR was 3 months, and the median time from CCR to BC was 4 months. BC phenotype was lymphoid in 2 patients, myeloid in 3 patients (including 2 patients who had extramedullary localization), and biclonal in 1 patient. Karyotype evolution was detected in 4 patients, whereas a Ph-positive/Ph-negative mosaicism was evident in all 6 patients. One patient presented an M351T mutation. The overall median survival was 3 months.
  
  
  CONCLUSIONS
  Sudden BC generally is an uncommon phenomenon that may be relatively frequent in patients with CML who receive imatinib. Clinical and biologic features also seem to characterize this peculiar type of abrupt disease evolution, which intervenes in patients' response to this drug. Close monitoring of disease markers and full disease eradication are warranted.
authors.affiliation: Department of Cellular Biotechnology andHematology, University La Sapienza, Rome, Italy. alimena@bce.uniroma1.it
authors.forename: Giuliana
authors.initials: G
authors.lastname: Alimena
authors.forename: Massimo
authors.initials: M
authors.lastname: Breccia
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.forename: Ida
authors.initials: I
authors.lastname: Carmosino
authors.forename: Eleonora
authors.initials: E
authors.lastname: Russo
authors.forename: Francesca
authors.initials: F
authors.lastname: Biondo
authors.forename: Daniela
authors.initials: D
authors.lastname: Diverio
authors.forename: Marco
authors.initials: M
authors.lastname: Mancini
authors.forename: Mauro
authors.initials: M
authors.lastname: Nanni
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate