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Blood, 1 January 2008, Vol. 111, No. 1, pp. 94-100.
Prepublished online as a Blood First Edition Paper on September 25, 2007; DOI 10.1182/blood-2007-06-097444.
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CLINICAL TRIALS AND OBSERVATIONS
Cytogenetically defined myelodysplasia after melphalan-based autotransplantation for multiple myeloma linked to poor hematopoietic stem-cell mobilization: the Arkansas experience in more than 3000 patients treated since 1989
Bart Barlogie1,
Guido Tricot1,
Jeff Haessler2,
Frits van Rhee1,
Michele Cottler-Fox1,3,
Elias Anaissie1,
James Waldron3,
Mauricio Pineda-Roman1,
Raymond Thertulien1,
Maurizio Zangari1,
Klaus Hollmig1,
Abid Mohiuddin1,
Yazan Alsayed1,
Antje Hoering2,
John Crowley2, and
Jeffrey Sawyer1,3
1 Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock;
2 Cancer Research and Biostatistics, Seattle, WA; and
3 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock
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 3077 patients undergoing high-dose therapy (HDT). MDS-associated cytogenetic abnormalities (MDS-CAs) were observed in 105 of 2418 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 106/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.
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