title: Increased incidence of transformation and myelodysplasia/acute leukemia in patients with Waldenström macroglobulinemia treated with nucleoside analogs.
abstract: OBJECTIVE
  Nucleoside analogs (NAs) are considered as appropriate agents in the treatment of Waldenström macroglobulinemia (WM), a lymphoplasmacytic lymphoma. Sporadic reports on increased incidence of transformation to high-grade non-Hodgkin's lymphoma and development of therapy-related myelodysplasia/acute leukemia (t-MDS/AML) among patients with WM treated with NAs prompted us to examine the incidence of such events in a large population of patients with WM.
  
  
  METHODS
  We examined the incidence of these events in 439 patients with WM, 193 and 136 of whom were previously treated with and without an NA, respectively, and 110 of whom had similar long-term follow-up without treatment. The median follow-up for all patients was 5 years.
  
  
  RESULTS
  Overall, 12 patients (6.2%) either developed transformation (n = 9; 4.7%) or developed t-MDS/AML (n = 3; 1.6%) among NA-treated patients, compared with one patient (0.4%) who developed transformation in the non-NA treated group (P < .001); no such events occurred among untreated patients. Transformation and t-MDS/AML occurred at a median of 5 years from onset of NA therapy. The median survival of NA-treated patients who developed transformation did not differ from other NA-treated patients as a result of effective salvage treatment used for transformed disease. However, all NA-treated patients who developed t-MDS/AML died at a median of 5 months.
  
  
  CONCLUSIONS
  These data demonstrate an increased incidence of disease transformation to high-grade NHL and the development of t-MDS/AML among patients with WM treated with NAs.
authors.affiliation: Bing Center for Waldenstrom's Macroglobulinemia, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Jacob
authors.initials: J
authors.lastname: Soumerai
authors.forename: Aldo
authors.initials: A
authors.lastname: Roccaro
authors.forename: Evdoxia
authors.initials: E
authors.lastname: Hatjiharissi
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Hunter
authors.forename: Robert
authors.initials: R
authors.lastname: Manning
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Ciccarelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Sacco
authors.forename: Leukothea
authors.initials: L
authors.lastname: Ioakimidis
authors.forename: Sophia
authors.initials: S
authors.lastname: Adamia
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Moreau
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Patterson
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.forename: Steven P
authors.initials: SP
authors.lastname: Treon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002699:Chlorambucil / Q000627:therapeutic use; D017338:Cladribine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000473:pathology*; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000473:pathology*; D009705:Nucleosides / Q000627:therapeutic use*; D012189:Retrospective Studies; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*
chemical_list: D009705:Nucleosides; D002699:Chlorambucil; D017338:Cladribine; D014740:Vidarabine; C024352:fludarabine