title: Secondary myelodysplastic syndrome and acute myelogenous leukemia are significant complications following autologous stem cell transplantation for lymphoma.
abstract: Secondary myelodysplastic syndrome (sMDS) and acute myelogenous leukemia (AML) have been recognized with increasing frequency following autologous stem cell transplantation (ASCT). A retrospective analysis of 230 consecutive patients with Hodgkin's lymphoma (HL, 64) and non-Hodgkin's lymphoma (NHL, 166) who underwent ASCT was conducted to assess the incidence and risk factors for the development of sMDS/AML. At a median follow up of 41 months (range 0.1-177 months), 10 of 230 patients (4.3%) developed sMDS/AML. The 5-year-actuarial incidence of sMDS/AML was 13.1% and 5-year cumulative incidence by competing risk analysis was 4.2%. The median time to development of sMDS/AML was 39.9 months from the time of ASCT (range 12.1-62.0 months). Complex karyotypes at diagnosis of sMDS/AML included structural anomalies and/or loss of chromosome 5 (eight patients), 7 (five patients), 17 (two patients) and 20 (two patients). All patients subsequently died, at a median of 6.8 months (range 0-39.9) from diagnosis of sMDS/AML. Fluorescent in situ hybridization (FISH) analysis for -5/5q- and -7/7q- were normal in all six patients whose pre-ASCT bone marrow was available for testing. Five of the six had samples available for testing at diagnosis of sMDS/AML and all had abnormal FISH results. By univariate statistical analysis, male gender (P=0.01), prior alkylating agents (mechlorethamine for HL, P=0.001 and cyclophosphamide for NHL, P=0.05) and the number of prior treatment regimens (P=0.04) were significantly associated with the development of sMDS/AML. Given the relatively low incidence rate of sMDS/AML, these analyses are primarily exploratory in nature but provide some insight into relevant risk factors and illustrate the risk of developing sMDS/AML after myeloablative conditioning and ASCT for lymphoma.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester MN 55905, USA.
authors.forename: R
authors.initials: R
authors.lastname: Howe
authors.forename: I N M
authors.initials: IN
authors.lastname: Micallef
authors.forename: D J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: S M
authors.initials: SM
authors.lastname: Ansell
authors.forename: G W
authors.initials: GW
authors.lastname: Dewald
authors.forename: A
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: D A
authors.initials: DA
authors.lastname: Gastineau
authors.forename: M A
authors.initials: MA
authors.lastname: Gertz
authors.forename: S M
authors.initials: SM
authors.lastname: Geyer
authors.forename: C A
authors.initials: CA
authors.lastname: Hanson
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.forename: M R
authors.initials: MR
authors.lastname: Litzow
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000473:pathology; D020732:Cytogenetic Analysis; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000209:etiology*; D008223:Lymphoma / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000209:etiology*; D011336:Probability; D012189:Retrospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000009:adverse effects; D014182:Transplantation, Autologous