Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3,000 patients treated since 1989

Blood. 2008 Jan 1;111(1):94-100. doi: 10.1182/blood-2007-06-097444. Epub 2007 Sep 25.


Myelodysplastic syndrome (MDS) is a well-recognized complication of chemotherapy for multiple myeloma (MM). Serial bone marrow metaphase examinations were performed for MM restaging in 3,077 patients undergoing high-dose therapy (HDT). MDS-associated cytogenetic abnormalities (MDS-CAs) were observed in 105 of 2,418 patients in whom cytogenetic data were available after HDT. MDS-CAs occurred transiently in 72 patients and on 3 successive occasions (persistent MDS-CAs) in 33 patients, for 10-year estimates of 4% and 2%, respectively; only 21 patients developed overt clinical MDS and 5, acute myeloblastic leukemia (AML). MDS-CA development was linked to lower CD34 yield at collection, longer time interval from MM diagnosis to HDT, older age, and lower platelet recovery after HDT; persistent MDS-CAs were predicted by CD34 yield of less than 3 x 10(6)/kg and need for more than 2 apheresis procedures. Applying a tertile frequency distribution over time to all 105 patients with MDS-CAs, its detection early after HDT was associated with longer time interval from diagnosis and low pre-HDT platelet count (likely resulting from pre-HDT damage), whereas late-onset MDS-CAs were noted among patients treated with Total Therapy 2 and Total Therapy 3 that applied post-HDT consolidation chemotherapy (suggesting possible post-HDT damage). While the risk of MDS-CAs was low and clinical MDS occurred infrequently, monitoring after post-HDT consolidation chemotherapy appears warranted.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Distribution
  • Arkansas / epidemiology
  • Chromosome Aberrations
  • Databases, Factual
  • Follow-Up Studies
  • Hematopoietic Stem Cell Mobilization / adverse effects*
  • Hematopoietic Stem Cell Mobilization / methods
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / mortality
  • Melphalan / adverse effects*
  • Metaphase
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Myeloablative Agonists / adverse effects*
  • Myelodysplastic Syndromes / etiology*
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / mortality
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Transplantation, Autologous / adverse effects*
  • Transplantation, Autologous / methods


  • Myeloablative Agonists
  • Melphalan