title: Therapy-related acute myelogenous leukemia and myelodysplastic syndrome in patients with acute lymphoblastic leukemia treated with the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimens.
abstract: BACKGROUND
  Secondary malignancies including myeloid neoplasms occur infrequently in acute lymphoblastic leukemia (ALL) and to the authors' knowledge have not been as well documented in adults as in children.
  
  
  METHODS
  A total of 641 patients with de novo ALL who were treated with the hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen or its variants were analyzed.
  
  
  RESULTS
  Sixteen patients (2.49%) developed secondary acute myelogenous leukemia (AML) (6 patients) or myelodysplastic syndrome (MDS) (10 patients). At the time of ALL diagnosis, the median age was 53 years; cytogenetics were normal in 11 patients, pseudo-diploidy with del(2) in 1 patient, t(9;22) in 1 patient, and unavailable in 3 patients. Frontline therapy included hyper-CVAD in 7 patients, hyper-CVAD with rituximab in 8 patients, and hyper-CVAD with imatinib in 1 patient. Karyotype at time of AML/MDS diagnosis was -5, -7 in 9 patients, normal in 1 patient, complex in 1 patient, inv(11) in 1 patient, t(4;11) in 1 patient, del(20) in 1 patient, and unavailable in 2 patients. Secondary AML/MDS developed at a median of 32 months after ALL diagnosis. Cytarabine plus anthracycline-based treatment was given to 12 patients with AML and high-risk MDS. One patient with MDS received arsenic trioxide, 1 received clofarabine, and 2 received decitabine. Response to treatment was complete remission in 3 patients, partial remission in 6 patients, and no response in 6 patients; 1 patient was untreated. Eight patients (1 with AML and 7 with MDS) underwent allogeneic stem cell transplantation, and all but 2 died at a median of 3 months (range, 0.5-11 months) after transplantation. The median overall survival after a diagnosis of secondary AML and MDS was 9.25 months (range, 1+ to 26+ months).
  
  
  CONCLUSIONS
  Secondary AML and MDS occur infrequently in adult patients with de novo ALL treated with the hyper-CVAD regimens, and response to therapy is poor.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Dushyant
authors.initials: D
authors.lastname: Verma
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Charles
authors.initials: C
authors.lastname: Koller
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide